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The collateral system of the medial nucleus of the trapezoid body of the cat, its neuronal architecture and relation to the olivo-cochlear bundle
288
BRAIN RESEARCH
T H E C O L L A T E R A L SYSTEM OF T H E M E D I A L NUCLEUS OF THE T R A P E Z O I D BODY OF T H E CAT, ITS N E U R O N A L A R C H I T E C T U R E AND R E L A T I O N TO T H E O L I V O - C O C H L E A R B U N D L E
D. KENT MOREST Department of Anatomy, Harvard Medical School, and Eaton-Peabody Laboratory o]' Auditory Physiology, Massachusetts Eye and Ear Infirmary, Boston, Mass. (U.S.A.)
(Accepted February 6th, 1968)
INTRODUCTION The medial nucleus of the trapezoid body is located in the hindbrain next to the superior olive. In it are found the calyces of Held. the large synaptic endings of certain auditory neurons of the cochlear nucleus. The function of the medial trapezoid nucleus is unknown. Knowledge of its structure and connections is incomplete. Several authors 6,9,19,22 have emphasized the prevalence of axonal collaterals in the trapezoid body, and there is a considerable literature on the calyx (see Ram6n y Cajal~a), but there has been no major contribution to the subject since 1898 (ref. 10). The early investigators made several significant discoveries about the structure of this region by using the rapid Golgi method in neonatal animals, but their treatment of the medial trapezoid nucleus was fragmentary. The present study is intended to provide a basis for future cytological studies of the scope that current neurophysiological interest in the region requires. The neuronal architecture of the medial trapezoid nucleus and of some neurons of the olivo-cochlear bundle has been analyzed with the rapid Golgi method after perfusionfixation. Several types of neurons are distinguished that are associated with different types of afferent endings. There is evidence that the medial trapezoid nucleus and the olivo-cochlear bundle could have a tonotopic organization. The study defines a system of axonal collaterals that would permit the neurons of the olivo-cochlear bundle to sample both the input and output signals of certain neurons in the medial trapezoid and medial superior olivary nuclei. MATERIALSAND METHODS The present findings apply to the brain stems of 69 cats, aged 1 h to 100 days, impregnated with the rapid Golgi method after perfusion'fixation is. The 3 following modifications of the published technique were made. (1) Artificial respiration was applied during the surgical procedures. (2) Instead of urea, sodium acetazolamide Brain Research, 9 (1968) 288-311
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
289
(200 mg/kg) was injected intravenously 20 min before the perfusions. Instead of receiving sodium nitrite, the cats were cooled to 25°C. (3) Most of the material was perfused at 25°C with a mixture of a 0.1 M dibasic potassium phosphate sodium acid phosphate buffer at pH 7.4 and 0.5~o polyvinylpyrrolidone (average molecular weight of 40,000), followed by a fixative, containing 0.25 ~i osmium tetroxide, 0.5'~ii polyvinylpyrrolidone, and 3 % potassium dichromate, buffered at pH 6.8. Unbroken series of celloidin sections were cut at 80-200 # parasagittally, transversely, horizon-
Fig. 1. The photomicrograph of a transverse section of the trapezoid body from a one-day-old cat shows the uniform impregnation of the neuropil routinely achieved in this study with the rapid Golgi method after perfusion-fixation. At this magnification (>; 75) and thickness of section (120 jr) individual elements are not resolved. Nevertheless, each nucleus is sharply delineated by the morphology of its neuropil. A, axons of the trapezoid body; B, medial trapezoid nucleus; C, medial (accessory) superior olivary nucleus; D, dorsomedial peri-olivary nucleus; E, ventral trapezoid (medial pre-olivary) nucleus; F, ventromedial peri-olivary group; G (arrow), dorsal peri-olivary group (retro-olivary mass22); H, lateral lobe of lateral (main) superior olivary nucleus; J, lateral trapezoid (lateral pre-olivary) nucleus; K, dorsolateral peri-olivary group (retro-olivary mass2Z). Thin arrows (left) indicate the path of some unimpregnated, myelinated abducens nerve rootlets. The large arrow (lower right) points laterally and parallel to the floor of the 4th ventricle. The scale is 100/<
Brain Research, 9 (1968) 288 311
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tally, or obliquely with respect to the floor of the 4th ventricle. Fifty additional brains were prepared by the Golgi-Cox, Golgi, Nissl, Klfiver, or protargol methods after immersion- or perfusion-fixation with formaldehyde, glutaraldehyde, ~w acrolein mixtures. The most extensive impregnations occurred after perfusion-fixation ~s in cats 2 weeks old or less, and these have been preferred for illustration. However, this study stresses morphological patterns that persist in animals of 14, 21, 28, 42, and 100 days of age. Only typical findings, repeatedly verified, are presented, unless otherwise stated. All of the observations and every detail of the illustrations have been checked repeatedly under oil immersion with a planapochromatic objective (N:A. 1.3) or with a semi-apochromatic objective (N.A. 1.25). The objective used to make each drawing is given in the legends. RESULTS
The medial nucleus of the trapezoid body occupies the region between the medial aspect of the abducens nerve root and the medial fiber capsule of the medial superior olivary nucleus (Figs. 1. B: 2. B: 4. A-D). It extends slightly more anterior and ventral than the latter but not quite as far dorsal. Dorsal to the medial trapezoid nucleus is the dorsomedial peri-olivary nucleus (Figs. 1, D; 4, E. F), the main source of the crossed olivo-cochlear tract. The latter nucleus is one of several groups of peri-olivary neurons, located at the dorsomedial, dorsal, dorsolateral, ventral, and ventromedial margins of the superior olivary nuclei (Figs. 1. D. F. G. J. K: 2, D). Ventral to the medial trapezoid nucleus is the ventral trapezoid nucleus, or medial pre-olivary nucleus of Cajal (Fig. 1. E): medially is the nucleus pontis centralis caudalis. In perfusion-fixed rapid Golgi preparations the uniform impregnation of the neuropil greatly facilitates the identification of the nuclei of the trapezoid body (Fig. 1). Each nucleus is sharply delineated by the morphology of its afferent axonal plexus, with consistently greater clarity than in the other types of preparations. If the medial trapezoid nucleus is defined as the neuropil containing the calyces of Held. then it contains several types of neurons and axonal endings. Medial trapezoid nucleus
Three types of neurons appear in the medial trapezoid nucleus: the principal neuron, the elongate neuron, and the steltate neuron. The principal neuron probably corresponds to neurons previously illustrated~0,20, 38. In the present material it is the most numerous neuronal type. It has a spherical or oval perikaryon, 20 # in diameter in Nissl-stained sections of the adult cat (Fig. 3A). There is nearly always a markedly eccentric nucleus or nucteolus (Figs. 3A; 7, C). The intra-cytoplasmic rod of Ram6n y Caja122, or the 'centrosome' of Rio Hortega 29, does not appear in the present material. There are 2-4 short, slender, richly branched dendrites (Figs. 4, B; 5, A). The branches of each dendrite form tufts, arranged in umbellate shapes, somewhat flattened in the horizontal plane, Brain Research, 9 (1968) 288-311
291
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
parallel to the trapezoid fibers• The branches are covered with spicules, spines, and long filiform appendages. There are relatively few appendages of the primary dendrites• The axon often forms thin collaterals a,~,-~z that arborize in restricted zones within the medial trapezoid nucleus (Figs. 5, A, right; 12, A). The post-synaptic structures contacted by these collaterals are not identified. The main axon leaves the nucleus laterally, often with one or more collaterals that course dorsal or ventral to the medial superior olivary nucleus. The ultimate destinations of the axon are not established at present. Previous observers mentioned collaterals to the ipsilateral ventral or lateral trapezoid nucleus ze, to the contralateral medial trapezoid nucleus ~, or crossing the midline zz. In the present material axonal collaterals consistently project to the ipsilateral dorsomedial peri-olivary nucleus, where they arborize in a characteristic pattern (Figs• 9, B; 12, B). These may correspond to certain collaterals depicted by Held a and Poljak ~. The multiple end-branches resemble a lacy lattice-work elongated
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Fig. 2. T h e p h o t o m i c r o g r a p h s h o w s a N i s s l - s t a i n e d section f r o m a n a d u l t cat in a p l a n e n e a r l y p a r a l l e l to the f l o o r o f the 4th ventricle• T h e a n t e r i o r ( r o s t r a l ) d i r e c t i o n is at the left• A, m e d i a l t r a p e z o i d b o d y ; B, m e d i a l t r a p e z o i d n u c l e u s ; C, m e d i a l s u p e r i o r o l i v a r y n u c l e u s ; D , l a t e r a l t r a p e z o i d n u c l e u s ; E, l a t e r a l t r a p e z o i d b o d y ; 6, a b d u c e n s n e r v e rootlets• T h e scale is 0.5 m m ( × 34). Brain
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Fig. 3. Nissl-stained neurons from an adult cat correspond to types distinguished x~ith the G{Hgi method on the basis of relative sizes and shapes of the perikarya. A, In the medial trapezoid nucleus the principal neurons typically have eccentric nuclei and fine Nissl substance; the elongate neurons (arrows) have a more centrally placed nucleus and coarser Nissl substance. B, In the same nucleus the large stellate neuron has thin Nissl bodies in a tigroid pattern. C, In the dorsomedial peri-olivar5 nucleus are small elongate neurons with scanty Nissl substance and often a cap of basophilic cytoplasm at one pole of the nucleus; the larger, radiate neuron has a inultipolar perikaryon with coarse clumps of Nissl substance. 24 ,u celloidin sections, cresyl violet. The scale is 20 H ( f 450).
in a direction parallel to the main stem o f the collateral. These collaterals establish a t o p o g r a p h i c a l c o r r e s p o n d e n c e between the two nuclei (Fig. 10). The neurons located m o s t v e n t r o m e d i a l l y ' ] n the medial t r a p e z o i d nucleus send their collaterals into a linear zone a l o n g the medial m a r g i n o f the d o r s o m e d i a l peri-olivary nucleus. The n e u r o n s located at successively m o r e d o r s o l a t e r a l p o s i t i o n s in the medial t r a p e z o i d nucleus send their collaterals to c o r r e s p o n d i n g l y m o r e lateral zones o f the d o r s o medial peri-olivary nucleus. The elongate neuron has an oval p e r i k a r y o n , slightly smaller than that o f the principal n e u r o n (Fig. 3A). Its nucleus is not eccentric in p r o p e r l y fixed tissue. A nuclear cap o f c y t o p l a s m i c b a s o p h i l i c m a t e r i a l sometimes a p p e a r s at one pole o f the cell. Its 4 or 5 d e n d r i t e s are quite long in a d o r s o v e n t r a l direction (Fig. 4, D ) and m a y even span the entire extent o f the nucleus, The s e c o n d a r y dendritic branches extend in several planes, b u t the shape o f the dendritic field is elongated, often with a d o r s o m e d i a l - t o - v e n t r o l a t e r a l o r i e n t a t i o n (Fig. 6). T h e p r i m a r y and s e c o n d a r y dendrites fairly bristle with short, filiform a p p e n d a g e s , which give t h e m a hirsute a p p e a r a n c e . T h e a x o n m a y form a s h o r t collateral before leaving the nucleus (Fig; 6, B). The stellate neuron is i n t e r m i n g l e d with principal a n d elongate neurons (Fig. Brain Research, 9 (1968) 288-311
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
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3B). It may correspond to the 'multipolar' cells mentioned by Taber 33 and Rasmussen 27. Its cell body measures about 25 by 35 /~ in Nissl-stained sections of the adult cat. The perikaryal cytoplasm is voluminous and contains darkly stained tigroid substance. The nucleus is rarely very eccentric. Its long, thick dendrites radiate in various directions, sometimes past the abducens nerve root or into the dorsomedial peri-olivary nucleus (Fig. 4, C). The dendrites have small, thin spines, but many fewer than those of the other neuronal types (Fig. 7). The impregnations of the axons extend only to the initial segments, which have no collaterals. The axonal endings of the medial trapezoid nucleus may be classified as those of the calyciferous axon, those of the afferent axonal plexus, and other axonal endings. The calyciferous axon forms the calyx of Held, the calycine collaterals, and the pre-calycine collaterals. The calyces of HeM are formed by the thickest axons, coursing laterally through the middle of the trapezoid body. In rapid Golgi preparations the calyx consists of finger-like extensions and petal-like expansions of the axon arranged in the shape of a cup (Figs. 6, M, N; 8, C). The following observations suggest that each calyx forms an axosomatic synapse with a principal neuron. In Golgi preparations, when a calyx is not impregnated too darkly, an oil immersion objective with a short depth of focus permits visualization of an osmium-stained perikaryon with an eccentric nucleus within the calyx. Only the principal neurons consistently have eccentric nuclei. In protargol impregnations the perikarya clearly associated with calyces nearly always have eccentric nuclei. In 6 particularly favorable Golgi preparations both a calyx and its enclosed neuron are impregnated (Figs. 5, A; 8, D). In each case the dendrites are typical of a principal neuron. In no instance in these preparations did a soma receive more than one calyx or a calyx engage more than one soma or engage the soma of a stellate or elongate neuron. Calycine collaterals. The periphery of the calyx, especially in older animals, forms processes that extend into the neighboring neuropil (Fig. 8). These thin collaterals often branch repeatedly and extensively in the medial trapezoid nucleus to form an axonal network, studded with many tiny, knobby endings (Fig. 8, B). The calycine collaterals are most consistently associated with principal neurons other than the one embraced by the parent calyx (Figs. 5, right; 8, A, B, D). The collaterals end in relation to cell bodies and the bases of the dendrites. The shortest branches occasionally extend to the dendrites of the same neuron that receives the parent calyx (Fig. 5, C). There are few examples of collaterals associated with stellate or elongate neurons (Fig. 8, E). Collin's 1 and Ramdn y Cajal's 23 isolated observations of a thin calycine process and of a small axosomatic ending in reduced silver preparations may represent calycine collaterals. Pre-calycine collaterals arise from the calyciferous axon, proximal to the calyx. There are 3 types. The first type is a slender collateral, which frequently branches from the calyciferous axon proximal to its calyx and ramifies in the medial trapezoid nucleus (Fig. 9, F). Veratti ~7 and Ramdn y Caja122 observed similar collaterals in the guinea pig but failed to find them in the cat. In the present material one example of such a
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20p Fig. 5. Principal neurons and axonal calyces, from transverse sections of the medial trapezoid nucleus of newborn cats. The rapid Golgi impregnations are rarely black or opaque but are usually red and translucent. At the right, thin collaterals of a calyx (in black) end in relation to the soma and dendrites of a principal neuron (coarse stipple). The axon of the latter (in blackI forms collateral sprouts at A, before leaving the section. A thick collateral of the calyciferous axon forms a calycoid ending, perhaps a rudimentary calyx, at B. At the left are two calyces, impregnated at the same time as the principal neurons receiving them. The profiles of the calyciferous axons are indicated by dense stippling. The borders of the calyces are unclear in transmitted light because of the darkness of the impregnation, but reflected light (epi-illumination) gives an impression of their forms. The short filiform appendages of the preterminal, calyciferous axons disappear in older cats. A calycine extension at C extends to the base of a dendrite of the principal neuron. A, axons of the principal neurons. Camera lucida, N.A. 1.25 (semi-apochromatic). Fig. 4. Neural elements of the medial trapezoid nucleus, the dorsomedial peri-olivary nucleus, and neighboring structures in a transverse section from a 14-day-old cat. A, B, C, D, axonal calyces, principal neuron, stellate neuron, and elongate neurons, respectively, of the medial trapezoid nucleus; E, F, radiate and elongate neurons, respectively, of the dorsomedial peri-olivary nucleus; G, large neurons of the nucleus pontis centralis caudalis; H, small neuron of the same nucleus: the axon forms collateral branches to the left of the perikaryon; J, neuron in the dorsal peri-olivary group; K, collateral of an axon crossing in the trapezoid body, which ascends in the root of the abducens nerve (6); L, ventromedial peri-olivary group; LSO, medial lobe of the lateral superior olivary nucleus; MSO, medial superior olivary nucleus; TV, ventral trapezoid nucleus; TVM, a medial extension of the preceding, associated with crossing trapezoid fibers. The arrow at the upper right is parallel to the median raphe. Camera lucida drawing of a rapid Golgi preparation, made with an apochromatic objective of numerical aperture (N.A.) 0.65. Brain Research, 9 (1968) 288-311
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20~ Fig. 6. Elongate neurons and various afferent collateral endings from transverse sections of the medial trapezoid nucleus of a 14-day-old cat. A, an elongate neuron with long dendrites oriented in a dorsomedial-to-ventrolateral direction; B, axon of an elongate neuron that forms terminal collaterals, before leaving the section in a ventrolaterat direction; C, E, F, G, H, J. K, afferent axons, traced from the medial part of the trapezoid body; collaterals of axons E-J end in relation to dendrites of the elongate neurons; L, axonal nexus, formed by collaterals of D and E; M, N. calyces. Circular profiles at the ends of some axons and dendrites in this and other figures indicate where they leave the sections. Rapid Golgi method Camera lucida. N.A. 1.3 (apochromatic).
Brain Research, 9 (1968) 288-311
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Fig. 7. A, a×on o f a large stel]ate neuron from a transverse section o f the medial trapezoid nucleus o f a ]4-day-old cat; B, part o f a peri-cellular axona] nest, which typically invests stellate neurons, from a transverse section o f a newborn cat ; C, perikaryon o f a principal neuron with an eccentric nucleus, stained with chrome-osmium in a parasagitta] section; D, stel]ate neuron from a parasagitta] section o f a 94-day-old cat. Rapid Golgi method. Camera ]ucida, N . A . ] .25 (semi-apochromatic).
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Fig. 8. Calycine collaterals from transverse sections of the medial trapezoid nucleus of 14-day-otd cats. A, calycine collaterals (in black), ending in relation to the soma and dendrite of a neighboring principal neuron (in outline); B, an extensive terminal network of calycine collaterals, associated with the profiles of osmium-stained perikarya (dashed lines); C, calyx of the classical description. clasping the stippled profile of an osmium-stained perikaryon ; D. simultaneous impregnations of a principal neuron (sparse stippling) and a calyx (dense stippling), the collaterals of which (dotted lines) closely associate with the osmium-stained profile of an adjacent perikaryon (dashed line); E, calyx with collaterals, one of which branches in relation to the dendrite (in black) o f an elongate neuron, the other, in relation to a dendrite of the principal neuron. Rapid Golgi method. Camera lucida, N.A. 1.3 (apochromatic ~.
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collateral ends in relation to the dendrites of a principal neuron. Collin ~ illustrated a similar collateral, apparently to a nearby neuronal perikaryon. However, the structures consistently contacted by these collaterals are as yet undetermined. The second type of pre-calycine collateral may be almost as thick as the calyciferous branch (Fig. 12, J). It usually forms a lateral continuation of the horizontal trunk of the calyciferous axon. Previous workers6,22,34,z7, 4° saw such collaterals, some of which end in the trapezoid nuclei 22. In the present material it is usually not possible to follow such a collateral to its ending. It may possibly project beyond the medial trapezoid nucleus. In two instances the collaterals end in thick finger-like branches, resembling a rudimentary calyx (Fig. 5, B). These are not true calyces, for they lack petal-shaped processes. In the present collection of over a thousand calyces there is only one example of a single fiber with 2 separate calyces. Such examples have been reported before6, 34,3s,39. The third and most commonly observed type of pre-calycine collateral usually ascends dorsally along the abducens nerve root, or just lateral to it (Fig. 9, D). It arborizes in relation to the dendrites of the dorsomedial peri-olivary nucleus in linear arrays of lacy end-branches (Fig. 11A). Various other collaterals of thick or thin axons in the trapezoid body, not clearly associated with calyces, ascend along the abducens root, before turning medially or laterally in the reticular formation to undetermined destinations (Fig. 4, K). The axonalplexus within the medial trapezoid nucleus is distinguished by 2 main varieties: the peri-dendritic plexus and the peri-cellular nest. The peri-demtritic plexus associates primarily with the dendrites of principal neurons (Fig. 9, C). Perhaps Held 7 observed a similar ending. It belongs to a mediumsized axon, coursing from the median raphe in the dorsal part of the trapezoid body. The axon arborizes in a rich, peri-dendritic plexus that recapitulates the dendritic pattern of the principal neuron. The plexus associates with more than one dendrite and with more than one principal neuron, but its ramifications extend in a narrow, horizontal zone. This results in a laminar arrangement of the peri-dendritic plexus across the dorsoventral axis of the nucleus (Fig. 10). The axonal trunk usually leaves the nucleus anterolaterally or posterolaterally, often to go to the medial superior olivary nucleus. In fact a large part, if not all, of the peri-dendritic plexus is formed by collaterals of the afferent axons projecting to the medial region of the medial superior olivary nucleus. The axon also forms some sparsely branched collaterals, associated with the radiating dendrites of the dorsomedial peri-olivary nucleus or the stellate dendrites of the medial trapezoid nucleus. The peri-cellular nest belongs to a fine axon, coursing laterally through the middle of the trapezoid body (Fig. 12, K). The axon arborizes in an extensive peri-cellular nest, consisting of a network of fine, short branches with numerous small boutons, which virtually envelopes the perikarya and dendrites of stellate neurons (Fig. 7, B). More than one axon contributes to the terminal nest surrounding a single neuron (Fig. 12, K). A single axon typically contributes to a number of scattered pericellular nests in no apparent order. A similar ending may have been observed previously 7,gA°,2°,z7. La Villa lo also observed axonal nests in the ventral trapezoid nucleus. Brain Research, 9 (1968) 288-311
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Other axonal endings in the medial trapezoid nucleus are the long or short, sparsely branched collaterals of the different axons passing through the trapezoid body to the medial superior olivary nucleus, the ventral trapezoid nucleus, or other destinations (Fig. 6). Some of these, including afferents to the medial superior olive, end in relation to the dendrites of the elongate neurons (Fig. 6, E-J). There are a few examples of collaterals of the peri-cellular nests and of calycine collaterals, projecting to elongate neurons (Fig. 8, E). However, the present findings do not establish exclusive relationships of these collaterals with the elongate neuron. Many very fine, sparsely branched axons seem to end primarily in the medial trapezoid nucleus, and not as side-branches of axons passing through the nucleus (Fig. 6, C). These often may be traced back as far as the medial trapezoid body. It is not possible to rule out an ipsilateral origin for some of the axonal endings mentioned in this paragraph. Tricomi-Allegra 34 observed that axonal collaterals of neurons in the adjacent homolateral reticular formation sometimes ramify in the medial trapezoid nucleus. Dorsomedial peri-olivary nucleus The dorsomedial peri-olivary nucleus is one of several peri-olivary groups s. It corresponds to the dorsomedial 'Nebenmasse' of Hofmann 8, the retro-trapezoidal cells of Poljak 19, and the retro-olivary multipolar cells of Rasmussen24,26, 2s that form the crossed olivo-cochlear tract. The nucleus extends medially to the medial aspect of the abducens nerve root and dorsally to a level with the dorsalmost edge of the lateral superior olivary nucleus (Figs. 1, D; 4, E, F). Ventrally it is co-extensive with the medial trapezoid nucleus. Some of the dendritic branches from the dorsomedially adjacent nucleus pontis centralis caudalis penetrate its neuropil (Fig. 4, G). Two types of neurons appear in the dorsomedial peri-olivary nucleus (Figs. 4, E, F). In the present material the axons of neither neuronal type can be traced beyond the initial segment. The elongate neuron is the more common type. It has a small perikaryon with scanty cytoplasm. The Nissl substance is faintly stained except for a thin, dark peri-nuclear cap (Fig. 3C). Its elongated dendrites extend parallel to the dorsomedial border of the medial superior olivary nucleus (Figs. 4, F; 11 A, E). Its slender dendrites have a modest number of short, jagged appendages (Fig. 11 B, G), lending it a feathery appearance, distinct from the larger elongate neuron of the medial trapezoid nucleus.
Fig. 9. Axonal collaterals in a transverse plane of the medial trapezoid nucleus of a newborn cat. The principal neuron in the upper right actually appears in an adjacent section. A, collaterals of the principal neuron that leave the section in a ventrolateral direction; B, collateral of the preceding, arborizing in the dorsomedial peri-olivary nucleus; C, afferent axon of the medial trapezoid body, crossing the myelin sheaths of the abducens rootlet (6) and the dorsomedial peri-olivary nucleus to form the type of terminal arborization consistently associated with the dendrites of principal neurons; D, collateral of a calyciferous axon in the medial trapezoid nucleus, which ramifies in the dorsomedial peri-olivary nucleus; E, afferent axon arborizing in this nucleus; F, collaterals of calyciferous axons ending in the medial trapezoid nucleus; G, large solitary process of a calyx; H, short collaterals of a calyx; J, collateral growth cones. Rapid Golgi method. Camera lucida, N.A. 1.25 (semi-apochromatic).
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Some of the dendrites extend ventrally along the a b d u c e n s nerve root or along lb.e medial aspect of the medial superior olivary nucleus. The axon usually leaves the nucleus in a dorsal direction.
The radiate neuron, the second n e u r o n a l type, has a larger cell body (Fig. 11 A, D). Its nucleus is relatively larger, a n d its perikaryal cytoplasm, relatively smaller, t h a n in the stellate n e u r o n of the medial trapezoid nucleus (Fig. 3C). It contains coarse clumps of Nissl material, lts long, radiating dendrites have a moderate n u m b e r of thin spines (Fig. 11 B, A). The dendrites frequently extend beyond the confines of the nucleus into the reticular f o r m a t i o n or the medial trapezoid nucleus (Fig. 4. E). q-he shape of this n e u r o n resembles that of the stellate n e u r o n of the medial trapezoid nucleus, but it is smaller. Afferent plexus. Like the stellate n e u r o n of the medial trapezoid nucleus, the
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Fig. 10. The topographical correspondence between the medial superior olivary, medial trapezoid. and dorsomedial peri-olivary nuclei, as seen in the transverse plane from a newborn cat. X. Y. Z. axons of the medial trapezoid body, projecting to the medial region of the medial superior olivary nucleus (MSO) in a dorsoventral tonotopic sequence4~. contribute collaterals to the peri-dendritic plexus of the medial trapezoid nucleus, also in a dorsoventral sequence. The basal turn of the cochlea is represented most ventrally. A, B, C. the main axons of principal neurons in the medial trapezoid nucleus, before leaving the section laterally, send collaterals, a. b. c, to the dorsomediat peri-olivary nucleus, so that the dorsal-to-ventral extent of the former is projected across the lateral-to-medial axis of the latter. The cells corresponding to B, b and C, c were taken from adjacent sections but retain their relative positions in the drawing. The scale at the upper left is parallel to the median raphe. P, pyramid. Camera lucida. N.A. 0.65 (apochromaticJ.
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radiate neuron is associated with a peri-cellular axonal nest (Figs. l lA, F; liB, A F). This is formed chiefly by collaterals from peri-cellular nests of the medial trapezoid nucleus. They ascend dorsally as delicate, vertical strands in figures recalling lacy arabesques (Fig. 12, K, L, M). The neuropil of the dorsomedial peri-olivary nucleus is further distinguished by a plexus of other axonal collaterals from the medial trapezoid nucleus (Figs. 9, B, D; 11 ; 12, B, D, G). Their terminal branchings form orderly, linear strands, parallel to the meridians of the nucleus (Fig. 4, E, F). They end in relation to the dendrites of the elongate and radiate neurons. There are also freely arborizing endings of moderately fine axons that enter the nucleus directly medially (Fig. 12, N, S). Coarser axons, many of them crossing in the trapezoid body, enter the nucleus and form right-angle, vertical collaterals (Fig. 12, O R). The main axons continue laterally to the meJial superior olivary nucleus (Fig. 12, R). Some of these end on the marginal neurons of the latter nucleus (Fig. 12, T); others pass dorsal or ventral to it. The marginal neurons that send their axons dorsally into the reticular formation often form terminal axonal collaterals in the dorsomedial peri-olivary nucleus (Fig. 12, U). DISCUSSION The neuron.q/architecture of the medial trapezoid nucleus
The meclial trapezoid nucleus contains 3 types of neurons, each of which associates with a different constellation of afferent axonal endings. The cytological and geometrical properties of these neurons and their afferent endings impose certain limitations on the spatial and temporal patterns of signal activity that they are able to sustain and thus on the kinds of auditory information that they may be able to process. The principal neuron is characterized by compact, tufted dendrites, the secondary branches of which tend to elongate in the horizontal plane. One consequence of that is this, that the afferent synaptic field concentrates in a relatively compact volume, compared to the other neurons. A second consequence is that the secondary dendrites engage a relatively narrow segment of the horizontal layers of the peri-dendritic plexus. Analogous orientations of tufted dendrites and afferent axonal layers occur in the cochlear nucleus, the superior olive, the central nucleus of the posterior colliculus, and the ventral nucleus of the medial geniculate body, where they consistently relate to the tonotopic organization of the ascending auditory system (see Morest13,14,16). It seems likely that the tufted dendrites of the principal neurons and the horizontal layers of the peri-dendritic plexus also provide for a tonotopic organization, across the dorsoventral axis of the medial trapezoid nucleus. A large part of the peri-dendritic plexus is formed by collaterals of the axons projecting to the medial region of the medial superior olivary nucleus (Fig. 10). Previous studiesa2, 4~ demonstrated that these axons originate in the contralateral anteroventral cochlear nucleus and have a tonotopic sequence across the dorsoventral axis of the medial superior olivary nucleus, such that the basal turn of the cochlea is represented most Brain Research, 9 (1968) 288-311
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ventrally4L It follows that a tonotopic sequence of the peri-dendritic plexus would also exist in the medial trapezoid nucleus, such that the basal turn of the cochlea is represented most ventrally. The calyx ends on the cell body of the principal neuron. One may not completely rule out a relationship of calyces with stellate or elongate neurons. However, these neurons consistently associate with peri-cellular nests and types of endings other than calyces. The available evidence points to an origin of the calyciferous axon somewhere in the contralateral cochlear nucleus '~,11,19,32,44. Since the latter nucleus is tonotopically organized, and since the calyx is a highly localized ending, a tonotopic arrangement of calyces in the medial trapezoid nucleus may be anticipated. It would be surprising if that arrangement did not follow the same general order as that of the peri-dendritic plexus, such that the basal turn of the cochlea is represented most ventrally. Since the definitive calycine collaterals first appear after birth and persist in large numbers in the young cat, they are presumably mature, functional structures. These differ from the short calycine extensions along the cells receiving the parent calyces1,12,21-23, in that the calycine collaterals, for the most part, probably end on the perikarya of nearby principal neurons. Calyces may function as rapid relays with very high security. But slower activity in the calycine collaterals, as well as in the peri-dendritic plexus, must also involve the principal neuron. If the calyx is an excitatory synaptic ending, the collaterals could generate inhibitory or excitatory post-synaptic potentials. For, even if Dale's law applies, the reaction of the postsynaptic membrane could be either excitatory or inhibitory. This consideration is not trivial. If inhibitory, the calycine collaterals could generate an inhibitory surround, as related to the shape of a tuning-curve, for example. If excitatory, their slower activity could be involved in post-stimulus changes in synaptic potentials, as in 'on-off' responses. Of course, it is not possible to exclude that some small, axosomatic or axodendritic endings on principal neurons derive from the pre-calycine collaterals, the peri-dendritic plexus, the peri-cellular nest, or from several other types of thin axons (Fig. 6). In any case the collaterals of calyciferous axons provide for the degree and pattern of terminal axonal overlapping observed so far in the synaptically secure sensory pathways 16. The elongate neuron, in its long dorsoventral extent, encounters the collateral endings of many horizontal axons, including those projecting to the homolateral
Fig. 1 IA. Dorsomedial peri-olivary nucleus in a transverse section from a newborn cat. A, B, collaterals of calyciferous axons in the medial trapezoid nucleus ascending beside the abducens rootlet (6) to the dorsomedial peri-olivary nucleus; C, afferent axons to this nucleus ; D, E, F, radiate neuron, elongate neuron, and peri-cellular axonal nest, respectively, of this nucleus. Rapid Golgi method. Camera lucida, N.A. 1.0 (apochromatic). Fig. 11B. Details of the dorsomedial peri-olivary nucleus in a transverse section of a newborn cat. A, radiate neuron and associated afferent axonal plexus; B, point at which the impregnation of the distal dendrite assumes a red translucence, giving a striking clarification of the peri-dendritic axons: C, peri-cellular nest, mimicking the soma and dendritic trunks of a radiate neuron, formed by axons at D, E, F and collaterals of the peri-cellular nest at A; G, axon of an elongate neuron with associated afferent endings. Rapid Golgi method. Camera lucida, N.A. 1.3 (apochromatic).
Brain Research, 9 (1968) 288-311
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medial superior olivary nucleus from the contralateral cochlear nucleus. A n elongate n e u r o n may sample a wide segment of the frequency spectrum represented by those axons, because of their dorsoventral tonotopic order in this region. This is analogous to the elongate n e u r o n of the central nucleus of the posterior colliculus, in relation to the ascending layers of lemniscal axons la. Whether or not the elongate neuron has a broad t u n i n g curve, as might be expected, would depend on the relative n u m b e r s and locations in the afferent fiber spectrum of the excitatory and inhibitory synapses along its dendrites. This a r r a n g e m e n t should favor detection or s u m m a t i o n or averaging of signals over wide sectors of the afferent fiber system. Now open for exploration are the possibilities that this could provide for a measure of the stimulus intensity, sample the local level of afferent signal activity, or a c c o u n t for responses to noise and c o m b i n a t i o n s of tonal stimuli, perhaps in relation to acoustic reflexes.
The stellate neuron resembles other multipolar n e u r o n s with long, radiating dendrites in the nuclei of the reticular formation. This n e u r o n and the peri-cellular nest of afferent endings investing it do not seem especially well suited to preserve a t o n o t o p i c organization, because of their scattered locations in the nucleus and the degree of convergence of the afferent axons. Indeed the origin of the afferents has not been demonstrated, if a tonotopic order does exist, then it must have a different a r r a n g e m e n t than that of the peri-dendritic plexus. Even so, the spatio-temporal patterns of synaptic activity that can be attributed to the long, radiating dendrites of the stellate n e u r o n and to the peri-cellular nest must differ from those of the other neuronal types. C o m p a r e d to the principal neuron, the stellate n e u r o n could acc o m m o d a t e a more heterogeneous afferent i n p u t or perhaps an entirely different kind of auditory information.
The architecture o f the crossed olivo-cochlear neurons The crossed olivo-cochlear axons of the dorsomedial peri-olivary nucleus could come from the elongate n e u r o n s or the radiate n e u r o n s or both.
Elon.gate neuron. The l a m i n a r a r r a n g e m e n t of the afferent axonal plexus, parallel to the n a r r o w dendritic fields of the elongate neurons, probably preserves a tonotopic
Fig. 12. Principal features of the collateral system of the medial trapezoid nucleus in a transverse section from a newborn cat. A, axonal collateral of a principal neuron, ending in the medial trapezoid nucleus; B, axonal collaterals of the same neuron, ending in the dorsomedial peri-olivary nucleus; C, fractures of the same axon at the section's surface; its probable continuationforms more collaterals in the dorsomedial peri-olivary nucleus at D and H and returns to the medial trapezoid nucleus, before leaving the section at E; F, collateral of a calyciferous axon that arborizes in the dorsomedial peri-olivary nucleus at G; H, elongate neuron of this nucleus; J, thick pre-calycine collateral of undetermined destination; K, two axons contributing to peri-cellular nests that outline two stellate neurons (L) in the medial trapezoid nucleus and three radiate neurons (M) in the dorsomedial periolivary nucleus; N, afferent axon to this nucleus; O-S, axons coursing from the medial trapezoid body across the abducens rootlet (6) with collateral branches in the dorsomedial peri-olivary nucleus; one axon (R) also ends in relation to the dendrites of a marginal neuron (T) of the medial superior olivary nucleus (MSO); U, axon of the marginal neuron, leaving the section in a dorsal direction, after forming collaterals in the dorsomedial peri-olivary nucleus. Rapid Golgi method. Camera lucida, N.A. 1.0 (apochromatic).
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organization. Electrical recordings from the crossed olivo-cochlear bundlc indicate restricted, best-frequency bands for its individual units a. Their shape and orientation in the laminar framework of the nucleus imply that the elongate neurons ~vould likely support a tonotopic organization. Their contribution to the olivo-cochlear bundle could account for its best-frequency bands. The order of a tonotopic sequence in the nucleus might correspond to the sequential arrangement of the axonal collaterals from the principal neurons of the medial trapezoid nucleus (Fig. 10). If the collaterals assured a tonotopic correspondence between the two nuclei, then the layers of the dorsomedial peri-olivary nucleus would have a tonotopic sequence, such that the basal turn of the cochlea is represented most medially. Radiate neurons of the dorsomedial peri-olivary nucleus could also contribute to the olivo-cochlear bundle 2s and so account for the largest olivo-cochlear axons of 3/~ in diameter in the adult cat z6. If so, the olivo-cochlear units, corresponding to the large fibers, should differ from elongate neuronal units in some of their electrical responses, by virtue of their crosscross orientation in the axonal layers of the nucleus and their association with peri-cellular nests. For example, this could bc reflected in broader tuning-curves or in responses involving masking by noise bursts and two-tone inhibition. The possibility that scattered neurons in the reticular formation or in other peri-olivary groups or that stellate neurons in the medial trapezoid nucleus could contribute to the olivo-cochlear pathways cannot be ruled out at this time. On the other hand, such neurons, as well as radiate neurons in the dorsomedial peri-olivary nucleus, could integrate auditory signals ultimately involved in the acoustic reflex functions of motor cranial nerve nuclei. Auditory projections to the peri-olivary reticular formation exist 19,24, and certain neurons in the reticular formation do project to motor cranial nerve nuclei, including the abducens nucleus 3°;3~,4~. Valverde ~ reported collaterals of calyciferous axons that ramify in the nucleus reticutaris parvicellularis. Unfortunately, the illustrations cited by that author fail to show this. Rasmussen ~4 traced degenerated fibers to the abducens nucleus from a lesion of the medial trapezoid nucleus of a cat. However, the connections of these regions are not yet sufficiently clarified to form the basis of any definite idea of their possible roles in acoustico-motor reflexes. The collateral system
The crossed olivo-cochlear axons from the dorsomedial peri-olivary nucleus end on external hair cells in the cochlea and on neurons in the cochlear nucleus 'z5,26, where they may produce changes in primary and secondary unit activit:y~,3,4,31,a3. The collaterals of the calyciferous axon and of the principal neuron from the medial trapezoid nucleus would enable dorsomedial peri-olivary neurons t o sample both input and output signals of the principal neurons (Fig. 12, B, F, G). That could provide the structural basis for the operation of a physiological automatic-gain contlol of auditory signals relayed by the cochlear nucleus, if the olivo,cochlear bundle does indeed function in a feed-back system a. Such a relationship with the Brain Research, 9 (1968) 288-311
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olivo-cochlear bundle may also pertain to the peri-dendritic plexus and to the principal neuron of the medial trapezoid nucleus and the marginal neuron of the medial superior olivary nucleus by way of their respective collaterals to the dorsomedial peri-olivary nucleus. Analogous situations may obtain in the posterior colliculus, where the arrangements of axonal collaterals relate the ascending input and output signals to the descending cortico-collicular projections 17. The posterior colliculus, in turn, projects to the dorsomedial peri-olivary nucleus 24,25. The lack of significant retrograde degeneration in the medial trapezoid nucleus after ablations of the posterior colliculus32, 44 argues against a projection from the former to the latter. However, the collaterals of the efferent medial trapezoid axons could prevent retrograde degeneration. Another possible relation of the medial trapezoid nucleus to the efferent auditory pathways is its connection with the lateral superior olivary nucleus 6,2v, which, in turn, projects to the cochlear nucleus 25, but the types of neurons involved are unidentified. In the trapezoid body there seems to be a systematic arrangement, in which the collaterals of axons from the cochlear nucleus and the collaterals of the corresponding auditory neurons in the trapezoid body may be related to peri-olivary neurons. The peri-olivary neurons presumably participate in the function of the efferent auditory pathways and the olivo-cochlear bundle. The roles of this system of collaterals and of the peri-olivary neurons in the function of the efferent auditory pathways require further clarification. The collateral system of the medial trapezoid nucleus may supply information concerning both input and output signals of this nucleus to peri-olivary neurons, thereby completing a series of recurrent loops, the functions of which are still to be demonstrated. SUMMARY
In rapid Golgi preparations several types of neurons and axonal endings are revealed in the medial trapezoid nucleus. The principal neuron, with tufted dendrites, receives the calyx of Held and endings of a peri-dendritic plexus. An elongate neuron is associated with various collateral endings of axons passing through the nucleus. A stellate neuron is associated with a peri-cellular axonal nest. The terminal branches of the peri-dendritic plexus are arranged in horizontal layers, which may provide for a tonotopic organization of the principal neurons across the dorsoventral axis of the nucleus. The dorsomedial peri-olivary nucleus, representing an origin of the crossed olivo-cochlear tract, contains elongate and radiate neurons. Its afferent plexus has a laminar arrangement, which may relate to a tonotopic organization of the olivo-cochlear bundle. Its plexus is formed chiefly by collaterals of axons entering or leaving the medial trapezoid nucleus. Collaterals from the calyciferous and peridendritic axons and from the axons of the principal neurons may permit the dorsomedial peri-olivary nucleus to monitor both the auditory input and output of the principal neurons of the medial trapezoid nucleus.
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ACKNOWLEDGMEN1-S This work
was supported
NB 06115 to Harvard
by U.S.
Public
Health
Service
Research
Grant
University and by funds made available by PHS GRS Grant
F r 0 5 4 8 5 t o t h e M a s s a c h u s e t t s Eye a n d E a r I n f i r m a r y . I t is a p l e a s u r e to a c k n o w l e d g e t h e a i d o f M i s s P. P a l m e r a n d M r s . J. L a w r e n c e G r a e f .
REFERENCES 1 COLLIN, g.., Sur les arborisations p6ricellulaires dans le noyau du corps trapezoide, Bibliogr. anat., 14 (1905) 311-315. 2 DESMEDT, J. E., Auditory-evoked potentials from cochlea to cortex as influenced by activation of the efferent olivo-cochlear bundle, J. acoust. Soc. Amer., 34 (1962) 1478-1496. 3 F•x, J., Auditory activity in centrifugal and centripetal cochlear fibres in cat. A stud~, of a feedback system, Acta physiol, scand., 55, Suppl. 189 (1962) 1-68. 4 GALAMaOS, R., Suppression of auditory nerve activity by stimulation of efferent fibcr~ to cochlea. J. Neurophysiol., 19 (1956) 424-437. 5 HARRISON, J. M., AND IRVING, R., Nucleus of the trapezoid body: dual afferent innervation, Science, 143 (1964) 473~174. 6 HELD, H., Die centrale GehOrleitung, Arch. Anat. Physiol., Anat. Abt., (1893) 201-248. 7 HELD, H., Beitrage zur Structur der Nervenzelten und ihrer Forts~itze. Zweite Abhandlung, Arch. Anat. Physiol., Anat. Abt., (1897) 204-294. 8 HOFMANN. F., Die obere Olive der S~iugetiere nebst Bemerkungen tiber die Lageder Cochlearisendkerne. Eine vergleichend anatomische Studie, Arb. Neural. Inst. Univ. Wien, 14 0908) 76-328. 9 K(SLLIKER. A.. Handbuch der Gewebelehre des Menschen. Engelmann, Leipzig, 1896. Bd. 2. Auft. 6. p. 261. 10 LA VILLA. I.. Algunos detalles concernientes ~. la oliva superior y focos actisticos, Rev. trhnest. microer., 3 (1898) 75-83. 11 LEwv. F. H.. Degenerationsversuche am akustischen System des Kaninchens und der Kalze (Zugleich ein Beitrag zur Anwendung der Marchischen Methode). Folia neuro-bioL fLpz.J. 2 ( 1909/471-518. 12 MEYER. S.. Ober eine Verbindungsweise der Neuronen. Nebst Mitteilungen fiber die Technik und die Erfolge der Methode der subcutanen Methylenblauinjection. Arch. mikr. Anat.. 47 (1896) 734-748. 13 MOREST D. K., The neuronal architecture of the medial geniculate body of the cat. J. Anat. (Lond.), 98 (1964) 611-630. 14 MOREST D. K.. The laminar structure of the inferior colliculus of the cat. Anat. Rec.. 148 t 1964) 314. 15 MOREST D. K.. The probable significance of synaptic and dendritic patterns of the thalamic and midbrain auditory system, Anat. Rec.. 148 (1964) 390-391. 16 MOREST D. K., The laminar structure of the medial geniculate body of the cat. J. Anat. Lond.). 99 (1965) 143-160. 17 MOREST D . K . The cortical structure of the inferior quadrigeminal lamina of the cm. ~nat. Rec., 154 (1966) 389-390. 18 MOREST D. K.. AND MOREST, R. R.. Perfusion-fixation of the brain with chrome-osmium solutions for the rapid Golgi method, Amer. J. Anat., 118 (1966) 811-832. 19 POLJAK, S., Untersuchungen am Oktavussystem der S~iugetiere und an den mit diesem koordinierten motorischen Apparaten des Hirnstammes. Eine morphologisch-biologische Studie. J. Psychol. Neurol. (Lpz.), 32 (1926) 170-231. 20 RAMON Y CAJAL, S., Be#rag zum Studium der Medulla Oblongata, des Kleinhirns uml des Urst)rung,s der Gehirnnerven, Barth. Leipzig, 1896. p. 75 21 RAM6N Y CAJAL. S.. Le bleu de m6thyl6ne dans les centres nerveux. Rev. trirnest, microer.. 1 (1896) 21-82. 22 RAM6N V CAJAL, S., Histologie du Systdme Nerveux de l'Homme et des Vertdbrds, lnstituto Ram6n y Cajal, Madrid, 1909, Vol. 1, p. 774 (1952 reprint). Brain Research, 9 (1968) 288-311
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23 RAMON V CAJAL, S., Les preuves objectives de l'unit6 anatomique des cellules nerveuses, Trab. Inst. Cc(/al lnvest, biol., 29 (1934) 1 137. 24 RASMUSSEN, G. L., ]-he superior olivary peduncle and other fiber projections of the superior olivary complex, J. comp. Neurol., 84 (1946) 141-220. 25 RASMUSSEN,G. L., Efferent fibers of the cochlear nerve and cochlear nucleus. In G. L. RASMUSSEN AND W. WINDLE (Eds.), Neural Mechanisms oJ" the Auditory and Vestibular Systems, Thomas, Springfield, 1960, p. 105. 26 RASMUSSEN, G. l.., Anatomic relationships of the ascending and descending auditory systems. In W. S. FIELDS AND B. R. ALFORD (Eds.), Neurological Aspects of Auditory and Vestibular Disorders, Thomas, Springfield, 1964, p. I. 27 RASMUSSEN,G. L., Efferent connections of the cochlear nucleus. In A. B. GRAHAM (Ed.), Se,sorineural Hearing Processes and Disorders, Little, Brown, Boston, 1967, p. 61. 28 RASMUSSEN,G. L., Personal communication. 1967. 29 Rio HORTECIA, P. DEL, Estudios sobre el centrosoma de las c61ulas nerviosas y neur6glicas de los vertebrados, en sus formas normal y anormales, Trab. Inst. Cajal htvest, biol., 14 (1916) 117 153. 30 SCHEIBeL, M. E., AND SCHHUEL, A. B., Structural substrates for integrative patterns in the brain stem reticular core. In H. H. JASPERet al. (Eds.), Reticular Formation ~/the Brain, Little, Brown, Boston, 1958, p. 31. 31 STARR, A., AND WERNICK. J., Olivocochlear bundle regulation of spontaneous and tone-evoked activities of single units in cochlear nucleus, J. acoust. Soc. Amer., 42 (1967) l189. 32 STOVLeR,W. A., An experimental study of the cells and connections of the superior olivary complex of the cat, J. comp. Neurol., 98 (1953) 401 431. 33 TA~ER, E., The c~toarchitecture of the brain stem of the cat. I. Brain stem nuclei of cat, J. comp. Neurol., 116 ( 1961 ) 27 70. 34 TR1COMt-ALLEGRA,G., I calici di Held nci centri acustici, N~vraxe, 6 (1904) 156 189. 35 VALW:RDE, I". Reticular formation of the ports and medulla oblongata. A Golgi study, J. comp. Neurol., l16(1961) 71 100. 36 Vm VERDE,F., Reticular formation of the albino rat's brain stem. Cytoarchitecture and corticofugal connections, J. comp. Neurol., 119 (1962) 25-54. 37 VERATn, E., Su Alcune Particolaritgt di Struttura dei Centri Acustici nei Mammi]eri; Appunti eli Anatomia Microseopica, Tip. e Legatoria Cooperativa, Pavia, 1900. 38 VINCENZL L., Nuove ricerche sui calici di Held nel nucteo del corpo trapezoide, Anat. Anz., 18 (1900) 344-348. 39 VINCEr~Zl, L., Di alcuni nuovi fatti risguardanti la fina anatomia del nucleo del corpo trapezoide, Anat. Anz., 19 (1901) 359 364. 40 VINCENZI, L., Sui calici di Held, Anat. Ariz., 25 (1904) 519 526. 41 WALBERG, F., DO the motor nuclei of the cranial nerves receive corticofugal fibres? An experimental study in the cat, Brain, 80 (1957) 597 605. 42 WARR, W. B., Fiber degeneration following lesions in the anterior ventral cochlear nucleus of the cat, Exp. Neurol., 14 (1966) 453-474. 43 WIEDERHOLD, M. L., AND SWlW, S. H., Electrical stimulation of the crossed olivocochlear bundle its effect on responses of auditory-nerve fibers to tone bursts, J. acoust. Soc. Amer., 41 (1967) 1585-1586. 44 WINKLER, C., Manuel de Neurologie, Tome 1, Anatornie du Systkme Nerveux, IF Partie, L'Appa,'eil Nerveux du N. Trigeminus et celui du N. Octavus, Bohn, Haarlem, 1921, p. 237.
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BRAIN RESEARCH
T H E C O L L A T E R A L SYSTEM OF T H E M E D I A L NUCLEUS OF THE T R A P E Z O I D BODY OF T H E CAT, ITS N E U R O N A L A R C H I T E C T U R E AND R E L A T I O N TO T H E O L I V O - C O C H L E A R B U N D L E
D. KENT MOREST Department of Anatomy, Harvard Medical School, and Eaton-Peabody Laboratory o]' Auditory Physiology, Massachusetts Eye and Ear Infirmary, Boston, Mass. (U.S.A.)
(Accepted February 6th, 1968)
INTRODUCTION The medial nucleus of the trapezoid body is located in the hindbrain next to the superior olive. In it are found the calyces of Held. the large synaptic endings of certain auditory neurons of the cochlear nucleus. The function of the medial trapezoid nucleus is unknown. Knowledge of its structure and connections is incomplete. Several authors 6,9,19,22 have emphasized the prevalence of axonal collaterals in the trapezoid body, and there is a considerable literature on the calyx (see Ram6n y Cajal~a), but there has been no major contribution to the subject since 1898 (ref. 10). The early investigators made several significant discoveries about the structure of this region by using the rapid Golgi method in neonatal animals, but their treatment of the medial trapezoid nucleus was fragmentary. The present study is intended to provide a basis for future cytological studies of the scope that current neurophysiological interest in the region requires. The neuronal architecture of the medial trapezoid nucleus and of some neurons of the olivo-cochlear bundle has been analyzed with the rapid Golgi method after perfusionfixation. Several types of neurons are distinguished that are associated with different types of afferent endings. There is evidence that the medial trapezoid nucleus and the olivo-cochlear bundle could have a tonotopic organization. The study defines a system of axonal collaterals that would permit the neurons of the olivo-cochlear bundle to sample both the input and output signals of certain neurons in the medial trapezoid and medial superior olivary nuclei. MATERIALSAND METHODS The present findings apply to the brain stems of 69 cats, aged 1 h to 100 days, impregnated with the rapid Golgi method after perfusion'fixation is. The 3 following modifications of the published technique were made. (1) Artificial respiration was applied during the surgical procedures. (2) Instead of urea, sodium acetazolamide Brain Research, 9 (1968) 288-311
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289
(200 mg/kg) was injected intravenously 20 min before the perfusions. Instead of receiving sodium nitrite, the cats were cooled to 25°C. (3) Most of the material was perfused at 25°C with a mixture of a 0.1 M dibasic potassium phosphate sodium acid phosphate buffer at pH 7.4 and 0.5~o polyvinylpyrrolidone (average molecular weight of 40,000), followed by a fixative, containing 0.25 ~i osmium tetroxide, 0.5'~ii polyvinylpyrrolidone, and 3 % potassium dichromate, buffered at pH 6.8. Unbroken series of celloidin sections were cut at 80-200 # parasagittally, transversely, horizon-
Fig. 1. The photomicrograph of a transverse section of the trapezoid body from a one-day-old cat shows the uniform impregnation of the neuropil routinely achieved in this study with the rapid Golgi method after perfusion-fixation. At this magnification (>; 75) and thickness of section (120 jr) individual elements are not resolved. Nevertheless, each nucleus is sharply delineated by the morphology of its neuropil. A, axons of the trapezoid body; B, medial trapezoid nucleus; C, medial (accessory) superior olivary nucleus; D, dorsomedial peri-olivary nucleus; E, ventral trapezoid (medial pre-olivary) nucleus; F, ventromedial peri-olivary group; G (arrow), dorsal peri-olivary group (retro-olivary mass22); H, lateral lobe of lateral (main) superior olivary nucleus; J, lateral trapezoid (lateral pre-olivary) nucleus; K, dorsolateral peri-olivary group (retro-olivary mass2Z). Thin arrows (left) indicate the path of some unimpregnated, myelinated abducens nerve rootlets. The large arrow (lower right) points laterally and parallel to the floor of the 4th ventricle. The scale is 100/<
Brain Research, 9 (1968) 288 311
290
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tally, or obliquely with respect to the floor of the 4th ventricle. Fifty additional brains were prepared by the Golgi-Cox, Golgi, Nissl, Klfiver, or protargol methods after immersion- or perfusion-fixation with formaldehyde, glutaraldehyde, ~w acrolein mixtures. The most extensive impregnations occurred after perfusion-fixation ~s in cats 2 weeks old or less, and these have been preferred for illustration. However, this study stresses morphological patterns that persist in animals of 14, 21, 28, 42, and 100 days of age. Only typical findings, repeatedly verified, are presented, unless otherwise stated. All of the observations and every detail of the illustrations have been checked repeatedly under oil immersion with a planapochromatic objective (N:A. 1.3) or with a semi-apochromatic objective (N.A. 1.25). The objective used to make each drawing is given in the legends. RESULTS
The medial nucleus of the trapezoid body occupies the region between the medial aspect of the abducens nerve root and the medial fiber capsule of the medial superior olivary nucleus (Figs. 1. B: 2. B: 4. A-D). It extends slightly more anterior and ventral than the latter but not quite as far dorsal. Dorsal to the medial trapezoid nucleus is the dorsomedial peri-olivary nucleus (Figs. 1, D; 4, E. F), the main source of the crossed olivo-cochlear tract. The latter nucleus is one of several groups of peri-olivary neurons, located at the dorsomedial, dorsal, dorsolateral, ventral, and ventromedial margins of the superior olivary nuclei (Figs. 1. D. F. G. J. K: 2, D). Ventral to the medial trapezoid nucleus is the ventral trapezoid nucleus, or medial pre-olivary nucleus of Cajal (Fig. 1. E): medially is the nucleus pontis centralis caudalis. In perfusion-fixed rapid Golgi preparations the uniform impregnation of the neuropil greatly facilitates the identification of the nuclei of the trapezoid body (Fig. 1). Each nucleus is sharply delineated by the morphology of its afferent axonal plexus, with consistently greater clarity than in the other types of preparations. If the medial trapezoid nucleus is defined as the neuropil containing the calyces of Held. then it contains several types of neurons and axonal endings. Medial trapezoid nucleus
Three types of neurons appear in the medial trapezoid nucleus: the principal neuron, the elongate neuron, and the steltate neuron. The principal neuron probably corresponds to neurons previously illustrated~0,20, 38. In the present material it is the most numerous neuronal type. It has a spherical or oval perikaryon, 20 # in diameter in Nissl-stained sections of the adult cat (Fig. 3A). There is nearly always a markedly eccentric nucleus or nucteolus (Figs. 3A; 7, C). The intra-cytoplasmic rod of Ram6n y Caja122, or the 'centrosome' of Rio Hortega 29, does not appear in the present material. There are 2-4 short, slender, richly branched dendrites (Figs. 4, B; 5, A). The branches of each dendrite form tufts, arranged in umbellate shapes, somewhat flattened in the horizontal plane, Brain Research, 9 (1968) 288-311
291
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
parallel to the trapezoid fibers• The branches are covered with spicules, spines, and long filiform appendages. There are relatively few appendages of the primary dendrites• The axon often forms thin collaterals a,~,-~z that arborize in restricted zones within the medial trapezoid nucleus (Figs. 5, A, right; 12, A). The post-synaptic structures contacted by these collaterals are not identified. The main axon leaves the nucleus laterally, often with one or more collaterals that course dorsal or ventral to the medial superior olivary nucleus. The ultimate destinations of the axon are not established at present. Previous observers mentioned collaterals to the ipsilateral ventral or lateral trapezoid nucleus ze, to the contralateral medial trapezoid nucleus ~, or crossing the midline zz. In the present material axonal collaterals consistently project to the ipsilateral dorsomedial peri-olivary nucleus, where they arborize in a characteristic pattern (Figs• 9, B; 12, B). These may correspond to certain collaterals depicted by Held a and Poljak ~. The multiple end-branches resemble a lacy lattice-work elongated
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Fig. 2. T h e p h o t o m i c r o g r a p h s h o w s a N i s s l - s t a i n e d section f r o m a n a d u l t cat in a p l a n e n e a r l y p a r a l l e l to the f l o o r o f the 4th ventricle• T h e a n t e r i o r ( r o s t r a l ) d i r e c t i o n is at the left• A, m e d i a l t r a p e z o i d b o d y ; B, m e d i a l t r a p e z o i d n u c l e u s ; C, m e d i a l s u p e r i o r o l i v a r y n u c l e u s ; D , l a t e r a l t r a p e z o i d n u c l e u s ; E, l a t e r a l t r a p e z o i d b o d y ; 6, a b d u c e n s n e r v e rootlets• T h e scale is 0.5 m m ( × 34). Brain
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Fig. 3. Nissl-stained neurons from an adult cat correspond to types distinguished x~ith the G{Hgi method on the basis of relative sizes and shapes of the perikarya. A, In the medial trapezoid nucleus the principal neurons typically have eccentric nuclei and fine Nissl substance; the elongate neurons (arrows) have a more centrally placed nucleus and coarser Nissl substance. B, In the same nucleus the large stellate neuron has thin Nissl bodies in a tigroid pattern. C, In the dorsomedial peri-olivar5 nucleus are small elongate neurons with scanty Nissl substance and often a cap of basophilic cytoplasm at one pole of the nucleus; the larger, radiate neuron has a inultipolar perikaryon with coarse clumps of Nissl substance. 24 ,u celloidin sections, cresyl violet. The scale is 20 H ( f 450).
in a direction parallel to the main stem o f the collateral. These collaterals establish a t o p o g r a p h i c a l c o r r e s p o n d e n c e between the two nuclei (Fig. 10). The neurons located m o s t v e n t r o m e d i a l l y ' ] n the medial t r a p e z o i d nucleus send their collaterals into a linear zone a l o n g the medial m a r g i n o f the d o r s o m e d i a l peri-olivary nucleus. The n e u r o n s located at successively m o r e d o r s o l a t e r a l p o s i t i o n s in the medial t r a p e z o i d nucleus send their collaterals to c o r r e s p o n d i n g l y m o r e lateral zones o f the d o r s o medial peri-olivary nucleus. The elongate neuron has an oval p e r i k a r y o n , slightly smaller than that o f the principal n e u r o n (Fig. 3A). Its nucleus is not eccentric in p r o p e r l y fixed tissue. A nuclear cap o f c y t o p l a s m i c b a s o p h i l i c m a t e r i a l sometimes a p p e a r s at one pole o f the cell. Its 4 or 5 d e n d r i t e s are quite long in a d o r s o v e n t r a l direction (Fig. 4, D ) and m a y even span the entire extent o f the nucleus, The s e c o n d a r y dendritic branches extend in several planes, b u t the shape o f the dendritic field is elongated, often with a d o r s o m e d i a l - t o - v e n t r o l a t e r a l o r i e n t a t i o n (Fig. 6). T h e p r i m a r y and s e c o n d a r y dendrites fairly bristle with short, filiform a p p e n d a g e s , which give t h e m a hirsute a p p e a r a n c e . T h e a x o n m a y form a s h o r t collateral before leaving the nucleus (Fig; 6, B). The stellate neuron is i n t e r m i n g l e d with principal a n d elongate neurons (Fig. Brain Research, 9 (1968) 288-311
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
293
3B). It may correspond to the 'multipolar' cells mentioned by Taber 33 and Rasmussen 27. Its cell body measures about 25 by 35 /~ in Nissl-stained sections of the adult cat. The perikaryal cytoplasm is voluminous and contains darkly stained tigroid substance. The nucleus is rarely very eccentric. Its long, thick dendrites radiate in various directions, sometimes past the abducens nerve root or into the dorsomedial peri-olivary nucleus (Fig. 4, C). The dendrites have small, thin spines, but many fewer than those of the other neuronal types (Fig. 7). The impregnations of the axons extend only to the initial segments, which have no collaterals. The axonal endings of the medial trapezoid nucleus may be classified as those of the calyciferous axon, those of the afferent axonal plexus, and other axonal endings. The calyciferous axon forms the calyx of Held, the calycine collaterals, and the pre-calycine collaterals. The calyces of HeM are formed by the thickest axons, coursing laterally through the middle of the trapezoid body. In rapid Golgi preparations the calyx consists of finger-like extensions and petal-like expansions of the axon arranged in the shape of a cup (Figs. 6, M, N; 8, C). The following observations suggest that each calyx forms an axosomatic synapse with a principal neuron. In Golgi preparations, when a calyx is not impregnated too darkly, an oil immersion objective with a short depth of focus permits visualization of an osmium-stained perikaryon with an eccentric nucleus within the calyx. Only the principal neurons consistently have eccentric nuclei. In protargol impregnations the perikarya clearly associated with calyces nearly always have eccentric nuclei. In 6 particularly favorable Golgi preparations both a calyx and its enclosed neuron are impregnated (Figs. 5, A; 8, D). In each case the dendrites are typical of a principal neuron. In no instance in these preparations did a soma receive more than one calyx or a calyx engage more than one soma or engage the soma of a stellate or elongate neuron. Calycine collaterals. The periphery of the calyx, especially in older animals, forms processes that extend into the neighboring neuropil (Fig. 8). These thin collaterals often branch repeatedly and extensively in the medial trapezoid nucleus to form an axonal network, studded with many tiny, knobby endings (Fig. 8, B). The calycine collaterals are most consistently associated with principal neurons other than the one embraced by the parent calyx (Figs. 5, right; 8, A, B, D). The collaterals end in relation to cell bodies and the bases of the dendrites. The shortest branches occasionally extend to the dendrites of the same neuron that receives the parent calyx (Fig. 5, C). There are few examples of collaterals associated with stellate or elongate neurons (Fig. 8, E). Collin's 1 and Ramdn y Cajal's 23 isolated observations of a thin calycine process and of a small axosomatic ending in reduced silver preparations may represent calycine collaterals. Pre-calycine collaterals arise from the calyciferous axon, proximal to the calyx. There are 3 types. The first type is a slender collateral, which frequently branches from the calyciferous axon proximal to its calyx and ramifies in the medial trapezoid nucleus (Fig. 9, F). Veratti ~7 and Ramdn y Caja122 observed similar collaterals in the guinea pig but failed to find them in the cat. In the present material one example of such a
Brain Research, 9 (1968) 288-311
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20p Fig. 5. Principal neurons and axonal calyces, from transverse sections of the medial trapezoid nucleus of newborn cats. The rapid Golgi impregnations are rarely black or opaque but are usually red and translucent. At the right, thin collaterals of a calyx (in black) end in relation to the soma and dendrites of a principal neuron (coarse stipple). The axon of the latter (in blackI forms collateral sprouts at A, before leaving the section. A thick collateral of the calyciferous axon forms a calycoid ending, perhaps a rudimentary calyx, at B. At the left are two calyces, impregnated at the same time as the principal neurons receiving them. The profiles of the calyciferous axons are indicated by dense stippling. The borders of the calyces are unclear in transmitted light because of the darkness of the impregnation, but reflected light (epi-illumination) gives an impression of their forms. The short filiform appendages of the preterminal, calyciferous axons disappear in older cats. A calycine extension at C extends to the base of a dendrite of the principal neuron. A, axons of the principal neurons. Camera lucida, N.A. 1.25 (semi-apochromatic). Fig. 4. Neural elements of the medial trapezoid nucleus, the dorsomedial peri-olivary nucleus, and neighboring structures in a transverse section from a 14-day-old cat. A, B, C, D, axonal calyces, principal neuron, stellate neuron, and elongate neurons, respectively, of the medial trapezoid nucleus; E, F, radiate and elongate neurons, respectively, of the dorsomedial peri-olivary nucleus; G, large neurons of the nucleus pontis centralis caudalis; H, small neuron of the same nucleus: the axon forms collateral branches to the left of the perikaryon; J, neuron in the dorsal peri-olivary group; K, collateral of an axon crossing in the trapezoid body, which ascends in the root of the abducens nerve (6); L, ventromedial peri-olivary group; LSO, medial lobe of the lateral superior olivary nucleus; MSO, medial superior olivary nucleus; TV, ventral trapezoid nucleus; TVM, a medial extension of the preceding, associated with crossing trapezoid fibers. The arrow at the upper right is parallel to the median raphe. Camera lucida drawing of a rapid Golgi preparation, made with an apochromatic objective of numerical aperture (N.A.) 0.65. Brain Research, 9 (1968) 288-311
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20~ Fig. 6. Elongate neurons and various afferent collateral endings from transverse sections of the medial trapezoid nucleus of a 14-day-old cat. A, an elongate neuron with long dendrites oriented in a dorsomedial-to-ventrolateral direction; B, axon of an elongate neuron that forms terminal collaterals, before leaving the section in a ventrolaterat direction; C, E, F, G, H, J. K, afferent axons, traced from the medial part of the trapezoid body; collaterals of axons E-J end in relation to dendrites of the elongate neurons; L, axonal nexus, formed by collaterals of D and E; M, N. calyces. Circular profiles at the ends of some axons and dendrites in this and other figures indicate where they leave the sections. Rapid Golgi method Camera lucida. N.A. 1.3 (apochromatic).
Brain Research, 9 (1968) 288-311
297
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Fig. 7. A, a×on o f a large stel]ate neuron from a transverse section o f the medial trapezoid nucleus o f a ]4-day-old cat; B, part o f a peri-cellular axona] nest, which typically invests stellate neurons, from a transverse section o f a newborn cat ; C, perikaryon o f a principal neuron with an eccentric nucleus, stained with chrome-osmium in a parasagitta] section; D, stel]ate neuron from a parasagitta] section o f a 94-day-old cat. Rapid Golgi method. Camera ]ucida, N . A . ] .25 (semi-apochromatic).
Brain Research, 9 (1968) 288-311
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Fig. 8. Calycine collaterals from transverse sections of the medial trapezoid nucleus of 14-day-otd cats. A, calycine collaterals (in black), ending in relation to the soma and dendrite of a neighboring principal neuron (in outline); B, an extensive terminal network of calycine collaterals, associated with the profiles of osmium-stained perikarya (dashed lines); C, calyx of the classical description. clasping the stippled profile of an osmium-stained perikaryon ; D. simultaneous impregnations of a principal neuron (sparse stippling) and a calyx (dense stippling), the collaterals of which (dotted lines) closely associate with the osmium-stained profile of an adjacent perikaryon (dashed line); E, calyx with collaterals, one of which branches in relation to the dendrite (in black) o f an elongate neuron, the other, in relation to a dendrite of the principal neuron. Rapid Golgi method. Camera lucida, N.A. 1.3 (apochromatic ~.
Brain Research, 9 (1968) 288-311
COLLATERAL SYSTEM OF TRAPEZOID NUCLEUS
299
collateral ends in relation to the dendrites of a principal neuron. Collin ~ illustrated a similar collateral, apparently to a nearby neuronal perikaryon. However, the structures consistently contacted by these collaterals are as yet undetermined. The second type of pre-calycine collateral may be almost as thick as the calyciferous branch (Fig. 12, J). It usually forms a lateral continuation of the horizontal trunk of the calyciferous axon. Previous workers6,22,34,z7, 4° saw such collaterals, some of which end in the trapezoid nuclei 22. In the present material it is usually not possible to follow such a collateral to its ending. It may possibly project beyond the medial trapezoid nucleus. In two instances the collaterals end in thick finger-like branches, resembling a rudimentary calyx (Fig. 5, B). These are not true calyces, for they lack petal-shaped processes. In the present collection of over a thousand calyces there is only one example of a single fiber with 2 separate calyces. Such examples have been reported before6, 34,3s,39. The third and most commonly observed type of pre-calycine collateral usually ascends dorsally along the abducens nerve root, or just lateral to it (Fig. 9, D). It arborizes in relation to the dendrites of the dorsomedial peri-olivary nucleus in linear arrays of lacy end-branches (Fig. 11A). Various other collaterals of thick or thin axons in the trapezoid body, not clearly associated with calyces, ascend along the abducens root, before turning medially or laterally in the reticular formation to undetermined destinations (Fig. 4, K). The axonalplexus within the medial trapezoid nucleus is distinguished by 2 main varieties: the peri-dendritic plexus and the peri-cellular nest. The peri-demtritic plexus associates primarily with the dendrites of principal neurons (Fig. 9, C). Perhaps Held 7 observed a similar ending. It belongs to a mediumsized axon, coursing from the median raphe in the dorsal part of the trapezoid body. The axon arborizes in a rich, peri-dendritic plexus that recapitulates the dendritic pattern of the principal neuron. The plexus associates with more than one dendrite and with more than one principal neuron, but its ramifications extend in a narrow, horizontal zone. This results in a laminar arrangement of the peri-dendritic plexus across the dorsoventral axis of the nucleus (Fig. 10). The axonal trunk usually leaves the nucleus anterolaterally or posterolaterally, often to go to the medial superior olivary nucleus. In fact a large part, if not all, of the peri-dendritic plexus is formed by collaterals of the afferent axons projecting to the medial region of the medial superior olivary nucleus. The axon also forms some sparsely branched collaterals, associated with the radiating dendrites of the dorsomedial peri-olivary nucleus or the stellate dendrites of the medial trapezoid nucleus. The peri-cellular nest belongs to a fine axon, coursing laterally through the middle of the trapezoid body (Fig. 12, K). The axon arborizes in an extensive peri-cellular nest, consisting of a network of fine, short branches with numerous small boutons, which virtually envelopes the perikarya and dendrites of stellate neurons (Fig. 7, B). More than one axon contributes to the terminal nest surrounding a single neuron (Fig. 12, K). A single axon typically contributes to a number of scattered pericellular nests in no apparent order. A similar ending may have been observed previously 7,gA°,2°,z7. La Villa lo also observed axonal nests in the ventral trapezoid nucleus. Brain Research, 9 (1968) 288-311
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Other axonal endings in the medial trapezoid nucleus are the long or short, sparsely branched collaterals of the different axons passing through the trapezoid body to the medial superior olivary nucleus, the ventral trapezoid nucleus, or other destinations (Fig. 6). Some of these, including afferents to the medial superior olive, end in relation to the dendrites of the elongate neurons (Fig. 6, E-J). There are a few examples of collaterals of the peri-cellular nests and of calycine collaterals, projecting to elongate neurons (Fig. 8, E). However, the present findings do not establish exclusive relationships of these collaterals with the elongate neuron. Many very fine, sparsely branched axons seem to end primarily in the medial trapezoid nucleus, and not as side-branches of axons passing through the nucleus (Fig. 6, C). These often may be traced back as far as the medial trapezoid body. It is not possible to rule out an ipsilateral origin for some of the axonal endings mentioned in this paragraph. Tricomi-Allegra 34 observed that axonal collaterals of neurons in the adjacent homolateral reticular formation sometimes ramify in the medial trapezoid nucleus. Dorsomedial peri-olivary nucleus The dorsomedial peri-olivary nucleus is one of several peri-olivary groups s. It corresponds to the dorsomedial 'Nebenmasse' of Hofmann 8, the retro-trapezoidal cells of Poljak 19, and the retro-olivary multipolar cells of Rasmussen24,26, 2s that form the crossed olivo-cochlear tract. The nucleus extends medially to the medial aspect of the abducens nerve root and dorsally to a level with the dorsalmost edge of the lateral superior olivary nucleus (Figs. 1, D; 4, E, F). Ventrally it is co-extensive with the medial trapezoid nucleus. Some of the dendritic branches from the dorsomedially adjacent nucleus pontis centralis caudalis penetrate its neuropil (Fig. 4, G). Two types of neurons appear in the dorsomedial peri-olivary nucleus (Figs. 4, E, F). In the present material the axons of neither neuronal type can be traced beyond the initial segment. The elongate neuron is the more common type. It has a small perikaryon with scanty cytoplasm. The Nissl substance is faintly stained except for a thin, dark peri-nuclear cap (Fig. 3C). Its elongated dendrites extend parallel to the dorsomedial border of the medial superior olivary nucleus (Figs. 4, F; 11 A, E). Its slender dendrites have a modest number of short, jagged appendages (Fig. 11 B, G), lending it a feathery appearance, distinct from the larger elongate neuron of the medial trapezoid nucleus.
Fig. 9. Axonal collaterals in a transverse plane of the medial trapezoid nucleus of a newborn cat. The principal neuron in the upper right actually appears in an adjacent section. A, collaterals of the principal neuron that leave the section in a ventrolateral direction; B, collateral of the preceding, arborizing in the dorsomedial peri-olivary nucleus; C, afferent axon of the medial trapezoid body, crossing the myelin sheaths of the abducens rootlet (6) and the dorsomedial peri-olivary nucleus to form the type of terminal arborization consistently associated with the dendrites of principal neurons; D, collateral of a calyciferous axon in the medial trapezoid nucleus, which ramifies in the dorsomedial peri-olivary nucleus; E, afferent axon arborizing in this nucleus; F, collaterals of calyciferous axons ending in the medial trapezoid nucleus; G, large solitary process of a calyx; H, short collaterals of a calyx; J, collateral growth cones. Rapid Golgi method. Camera lucida, N.A. 1.25 (semi-apochromatic).
Brain Research, 9 (1968) 288-311
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Some of the dendrites extend ventrally along the a b d u c e n s nerve root or along lb.e medial aspect of the medial superior olivary nucleus. The axon usually leaves the nucleus in a dorsal direction.
The radiate neuron, the second n e u r o n a l type, has a larger cell body (Fig. 11 A, D). Its nucleus is relatively larger, a n d its perikaryal cytoplasm, relatively smaller, t h a n in the stellate n e u r o n of the medial trapezoid nucleus (Fig. 3C). It contains coarse clumps of Nissl material, lts long, radiating dendrites have a moderate n u m b e r of thin spines (Fig. 11 B, A). The dendrites frequently extend beyond the confines of the nucleus into the reticular f o r m a t i o n or the medial trapezoid nucleus (Fig. 4. E). q-he shape of this n e u r o n resembles that of the stellate n e u r o n of the medial trapezoid nucleus, but it is smaller. Afferent plexus. Like the stellate n e u r o n of the medial trapezoid nucleus, the
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Fig. 10. The topographical correspondence between the medial superior olivary, medial trapezoid. and dorsomedial peri-olivary nuclei, as seen in the transverse plane from a newborn cat. X. Y. Z. axons of the medial trapezoid body, projecting to the medial region of the medial superior olivary nucleus (MSO) in a dorsoventral tonotopic sequence4~. contribute collaterals to the peri-dendritic plexus of the medial trapezoid nucleus, also in a dorsoventral sequence. The basal turn of the cochlea is represented most ventrally. A, B, C. the main axons of principal neurons in the medial trapezoid nucleus, before leaving the section laterally, send collaterals, a. b. c, to the dorsomediat peri-olivary nucleus, so that the dorsal-to-ventral extent of the former is projected across the lateral-to-medial axis of the latter. The cells corresponding to B, b and C, c were taken from adjacent sections but retain their relative positions in the drawing. The scale at the upper left is parallel to the median raphe. P, pyramid. Camera lucida. N.A. 0.65 (apochromaticJ.
Brain Research, 9 (t968) 288-311
COLLATERALSYSTEMOF TRAPEZOIDNUCLEUS
303
radiate neuron is associated with a peri-cellular axonal nest (Figs. l lA, F; liB, A F). This is formed chiefly by collaterals from peri-cellular nests of the medial trapezoid nucleus. They ascend dorsally as delicate, vertical strands in figures recalling lacy arabesques (Fig. 12, K, L, M). The neuropil of the dorsomedial peri-olivary nucleus is further distinguished by a plexus of other axonal collaterals from the medial trapezoid nucleus (Figs. 9, B, D; 11 ; 12, B, D, G). Their terminal branchings form orderly, linear strands, parallel to the meridians of the nucleus (Fig. 4, E, F). They end in relation to the dendrites of the elongate and radiate neurons. There are also freely arborizing endings of moderately fine axons that enter the nucleus directly medially (Fig. 12, N, S). Coarser axons, many of them crossing in the trapezoid body, enter the nucleus and form right-angle, vertical collaterals (Fig. 12, O R). The main axons continue laterally to the meJial superior olivary nucleus (Fig. 12, R). Some of these end on the marginal neurons of the latter nucleus (Fig. 12, T); others pass dorsal or ventral to it. The marginal neurons that send their axons dorsally into the reticular formation often form terminal axonal collaterals in the dorsomedial peri-olivary nucleus (Fig. 12, U). DISCUSSION The neuron.q/architecture of the medial trapezoid nucleus
The meclial trapezoid nucleus contains 3 types of neurons, each of which associates with a different constellation of afferent axonal endings. The cytological and geometrical properties of these neurons and their afferent endings impose certain limitations on the spatial and temporal patterns of signal activity that they are able to sustain and thus on the kinds of auditory information that they may be able to process. The principal neuron is characterized by compact, tufted dendrites, the secondary branches of which tend to elongate in the horizontal plane. One consequence of that is this, that the afferent synaptic field concentrates in a relatively compact volume, compared to the other neurons. A second consequence is that the secondary dendrites engage a relatively narrow segment of the horizontal layers of the peri-dendritic plexus. Analogous orientations of tufted dendrites and afferent axonal layers occur in the cochlear nucleus, the superior olive, the central nucleus of the posterior colliculus, and the ventral nucleus of the medial geniculate body, where they consistently relate to the tonotopic organization of the ascending auditory system (see Morest13,14,16). It seems likely that the tufted dendrites of the principal neurons and the horizontal layers of the peri-dendritic plexus also provide for a tonotopic organization, across the dorsoventral axis of the medial trapezoid nucleus. A large part of the peri-dendritic plexus is formed by collaterals of the axons projecting to the medial region of the medial superior olivary nucleus (Fig. 10). Previous studiesa2, 4~ demonstrated that these axons originate in the contralateral anteroventral cochlear nucleus and have a tonotopic sequence across the dorsoventral axis of the medial superior olivary nucleus, such that the basal turn of the cochlea is represented most Brain Research, 9 (1968) 288-311
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ventrally4L It follows that a tonotopic sequence of the peri-dendritic plexus would also exist in the medial trapezoid nucleus, such that the basal turn of the cochlea is represented most ventrally. The calyx ends on the cell body of the principal neuron. One may not completely rule out a relationship of calyces with stellate or elongate neurons. However, these neurons consistently associate with peri-cellular nests and types of endings other than calyces. The available evidence points to an origin of the calyciferous axon somewhere in the contralateral cochlear nucleus '~,11,19,32,44. Since the latter nucleus is tonotopically organized, and since the calyx is a highly localized ending, a tonotopic arrangement of calyces in the medial trapezoid nucleus may be anticipated. It would be surprising if that arrangement did not follow the same general order as that of the peri-dendritic plexus, such that the basal turn of the cochlea is represented most ventrally. Since the definitive calycine collaterals first appear after birth and persist in large numbers in the young cat, they are presumably mature, functional structures. These differ from the short calycine extensions along the cells receiving the parent calyces1,12,21-23, in that the calycine collaterals, for the most part, probably end on the perikarya of nearby principal neurons. Calyces may function as rapid relays with very high security. But slower activity in the calycine collaterals, as well as in the peri-dendritic plexus, must also involve the principal neuron. If the calyx is an excitatory synaptic ending, the collaterals could generate inhibitory or excitatory post-synaptic potentials. For, even if Dale's law applies, the reaction of the postsynaptic membrane could be either excitatory or inhibitory. This consideration is not trivial. If inhibitory, the calycine collaterals could generate an inhibitory surround, as related to the shape of a tuning-curve, for example. If excitatory, their slower activity could be involved in post-stimulus changes in synaptic potentials, as in 'on-off' responses. Of course, it is not possible to exclude that some small, axosomatic or axodendritic endings on principal neurons derive from the pre-calycine collaterals, the peri-dendritic plexus, the peri-cellular nest, or from several other types of thin axons (Fig. 6). In any case the collaterals of calyciferous axons provide for the degree and pattern of terminal axonal overlapping observed so far in the synaptically secure sensory pathways 16. The elongate neuron, in its long dorsoventral extent, encounters the collateral endings of many horizontal axons, including those projecting to the homolateral
Fig. 1 IA. Dorsomedial peri-olivary nucleus in a transverse section from a newborn cat. A, B, collaterals of calyciferous axons in the medial trapezoid nucleus ascending beside the abducens rootlet (6) to the dorsomedial peri-olivary nucleus; C, afferent axons to this nucleus ; D, E, F, radiate neuron, elongate neuron, and peri-cellular axonal nest, respectively, of this nucleus. Rapid Golgi method. Camera lucida, N.A. 1.0 (apochromatic). Fig. 11B. Details of the dorsomedial peri-olivary nucleus in a transverse section of a newborn cat. A, radiate neuron and associated afferent axonal plexus; B, point at which the impregnation of the distal dendrite assumes a red translucence, giving a striking clarification of the peri-dendritic axons: C, peri-cellular nest, mimicking the soma and dendritic trunks of a radiate neuron, formed by axons at D, E, F and collaterals of the peri-cellular nest at A; G, axon of an elongate neuron with associated afferent endings. Rapid Golgi method. Camera lucida, N.A. 1.3 (apochromatic).
Brain Research, 9 (1968) 288-311
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medial superior olivary nucleus from the contralateral cochlear nucleus. A n elongate n e u r o n may sample a wide segment of the frequency spectrum represented by those axons, because of their dorsoventral tonotopic order in this region. This is analogous to the elongate n e u r o n of the central nucleus of the posterior colliculus, in relation to the ascending layers of lemniscal axons la. Whether or not the elongate neuron has a broad t u n i n g curve, as might be expected, would depend on the relative n u m b e r s and locations in the afferent fiber spectrum of the excitatory and inhibitory synapses along its dendrites. This a r r a n g e m e n t should favor detection or s u m m a t i o n or averaging of signals over wide sectors of the afferent fiber system. Now open for exploration are the possibilities that this could provide for a measure of the stimulus intensity, sample the local level of afferent signal activity, or a c c o u n t for responses to noise and c o m b i n a t i o n s of tonal stimuli, perhaps in relation to acoustic reflexes.
The stellate neuron resembles other multipolar n e u r o n s with long, radiating dendrites in the nuclei of the reticular formation. This n e u r o n and the peri-cellular nest of afferent endings investing it do not seem especially well suited to preserve a t o n o t o p i c organization, because of their scattered locations in the nucleus and the degree of convergence of the afferent axons. Indeed the origin of the afferents has not been demonstrated, if a tonotopic order does exist, then it must have a different a r r a n g e m e n t than that of the peri-dendritic plexus. Even so, the spatio-temporal patterns of synaptic activity that can be attributed to the long, radiating dendrites of the stellate n e u r o n and to the peri-cellular nest must differ from those of the other neuronal types. C o m p a r e d to the principal neuron, the stellate n e u r o n could acc o m m o d a t e a more heterogeneous afferent i n p u t or perhaps an entirely different kind of auditory information.
The architecture o f the crossed olivo-cochlear neurons The crossed olivo-cochlear axons of the dorsomedial peri-olivary nucleus could come from the elongate n e u r o n s or the radiate n e u r o n s or both.
Elon.gate neuron. The l a m i n a r a r r a n g e m e n t of the afferent axonal plexus, parallel to the n a r r o w dendritic fields of the elongate neurons, probably preserves a tonotopic
Fig. 12. Principal features of the collateral system of the medial trapezoid nucleus in a transverse section from a newborn cat. A, axonal collateral of a principal neuron, ending in the medial trapezoid nucleus; B, axonal collaterals of the same neuron, ending in the dorsomedial peri-olivary nucleus; C, fractures of the same axon at the section's surface; its probable continuationforms more collaterals in the dorsomedial peri-olivary nucleus at D and H and returns to the medial trapezoid nucleus, before leaving the section at E; F, collateral of a calyciferous axon that arborizes in the dorsomedial peri-olivary nucleus at G; H, elongate neuron of this nucleus; J, thick pre-calycine collateral of undetermined destination; K, two axons contributing to peri-cellular nests that outline two stellate neurons (L) in the medial trapezoid nucleus and three radiate neurons (M) in the dorsomedial periolivary nucleus; N, afferent axon to this nucleus; O-S, axons coursing from the medial trapezoid body across the abducens rootlet (6) with collateral branches in the dorsomedial peri-olivary nucleus; one axon (R) also ends in relation to the dendrites of a marginal neuron (T) of the medial superior olivary nucleus (MSO); U, axon of the marginal neuron, leaving the section in a dorsal direction, after forming collaterals in the dorsomedial peri-olivary nucleus. Rapid Golgi method. Camera lucida, N.A. 1.0 (apochromatic).
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organization. Electrical recordings from the crossed olivo-cochlear bundlc indicate restricted, best-frequency bands for its individual units a. Their shape and orientation in the laminar framework of the nucleus imply that the elongate neurons ~vould likely support a tonotopic organization. Their contribution to the olivo-cochlear bundle could account for its best-frequency bands. The order of a tonotopic sequence in the nucleus might correspond to the sequential arrangement of the axonal collaterals from the principal neurons of the medial trapezoid nucleus (Fig. 10). If the collaterals assured a tonotopic correspondence between the two nuclei, then the layers of the dorsomedial peri-olivary nucleus would have a tonotopic sequence, such that the basal turn of the cochlea is represented most medially. Radiate neurons of the dorsomedial peri-olivary nucleus could also contribute to the olivo-cochlear bundle 2s and so account for the largest olivo-cochlear axons of 3/~ in diameter in the adult cat z6. If so, the olivo-cochlear units, corresponding to the large fibers, should differ from elongate neuronal units in some of their electrical responses, by virtue of their crosscross orientation in the axonal layers of the nucleus and their association with peri-cellular nests. For example, this could bc reflected in broader tuning-curves or in responses involving masking by noise bursts and two-tone inhibition. The possibility that scattered neurons in the reticular formation or in other peri-olivary groups or that stellate neurons in the medial trapezoid nucleus could contribute to the olivo-cochlear pathways cannot be ruled out at this time. On the other hand, such neurons, as well as radiate neurons in the dorsomedial peri-olivary nucleus, could integrate auditory signals ultimately involved in the acoustic reflex functions of motor cranial nerve nuclei. Auditory projections to the peri-olivary reticular formation exist 19,24, and certain neurons in the reticular formation do project to motor cranial nerve nuclei, including the abducens nucleus 3°;3~,4~. Valverde ~ reported collaterals of calyciferous axons that ramify in the nucleus reticutaris parvicellularis. Unfortunately, the illustrations cited by that author fail to show this. Rasmussen ~4 traced degenerated fibers to the abducens nucleus from a lesion of the medial trapezoid nucleus of a cat. However, the connections of these regions are not yet sufficiently clarified to form the basis of any definite idea of their possible roles in acoustico-motor reflexes. The collateral system
The crossed olivo-cochlear axons from the dorsomedial peri-olivary nucleus end on external hair cells in the cochlea and on neurons in the cochlear nucleus 'z5,26, where they may produce changes in primary and secondary unit activit:y~,3,4,31,a3. The collaterals of the calyciferous axon and of the principal neuron from the medial trapezoid nucleus would enable dorsomedial peri-olivary neurons t o sample both input and output signals of the principal neurons (Fig. 12, B, F, G). That could provide the structural basis for the operation of a physiological automatic-gain contlol of auditory signals relayed by the cochlear nucleus, if the olivo,cochlear bundle does indeed function in a feed-back system a. Such a relationship with the Brain Research, 9 (1968) 288-311
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olivo-cochlear bundle may also pertain to the peri-dendritic plexus and to the principal neuron of the medial trapezoid nucleus and the marginal neuron of the medial superior olivary nucleus by way of their respective collaterals to the dorsomedial peri-olivary nucleus. Analogous situations may obtain in the posterior colliculus, where the arrangements of axonal collaterals relate the ascending input and output signals to the descending cortico-collicular projections 17. The posterior colliculus, in turn, projects to the dorsomedial peri-olivary nucleus 24,25. The lack of significant retrograde degeneration in the medial trapezoid nucleus after ablations of the posterior colliculus32, 44 argues against a projection from the former to the latter. However, the collaterals of the efferent medial trapezoid axons could prevent retrograde degeneration. Another possible relation of the medial trapezoid nucleus to the efferent auditory pathways is its connection with the lateral superior olivary nucleus 6,2v, which, in turn, projects to the cochlear nucleus 25, but the types of neurons involved are unidentified. In the trapezoid body there seems to be a systematic arrangement, in which the collaterals of axons from the cochlear nucleus and the collaterals of the corresponding auditory neurons in the trapezoid body may be related to peri-olivary neurons. The peri-olivary neurons presumably participate in the function of the efferent auditory pathways and the olivo-cochlear bundle. The roles of this system of collaterals and of the peri-olivary neurons in the function of the efferent auditory pathways require further clarification. The collateral system of the medial trapezoid nucleus may supply information concerning both input and output signals of this nucleus to peri-olivary neurons, thereby completing a series of recurrent loops, the functions of which are still to be demonstrated. SUMMARY
In rapid Golgi preparations several types of neurons and axonal endings are revealed in the medial trapezoid nucleus. The principal neuron, with tufted dendrites, receives the calyx of Held and endings of a peri-dendritic plexus. An elongate neuron is associated with various collateral endings of axons passing through the nucleus. A stellate neuron is associated with a peri-cellular axonal nest. The terminal branches of the peri-dendritic plexus are arranged in horizontal layers, which may provide for a tonotopic organization of the principal neurons across the dorsoventral axis of the nucleus. The dorsomedial peri-olivary nucleus, representing an origin of the crossed olivo-cochlear tract, contains elongate and radiate neurons. Its afferent plexus has a laminar arrangement, which may relate to a tonotopic organization of the olivo-cochlear bundle. Its plexus is formed chiefly by collaterals of axons entering or leaving the medial trapezoid nucleus. Collaterals from the calyciferous and peridendritic axons and from the axons of the principal neurons may permit the dorsomedial peri-olivary nucleus to monitor both the auditory input and output of the principal neurons of the medial trapezoid nucleus.
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ACKNOWLEDGMEN1-S This work
was supported
NB 06115 to Harvard
by U.S.
Public
Health
Service
Research
Grant
University and by funds made available by PHS GRS Grant
F r 0 5 4 8 5 t o t h e M a s s a c h u s e t t s Eye a n d E a r I n f i r m a r y . I t is a p l e a s u r e to a c k n o w l e d g e t h e a i d o f M i s s P. P a l m e r a n d M r s . J. L a w r e n c e G r a e f .
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