Organization of the mammalian thalamus and its relationships to the cerebral cortex

O R G A N I Z A T I O N OF T H E M A M M A L I A N T H A L A M U S A N D ITS R E L A T I O N S H I P S TO T H E C E R E B R A L C O R T E X JERZY E. ROSE, M.D. and CLINTON N. WOOLSEY,M.D. Departments of Physiology and Psychiatry, School of Medicine, The Johns Hopkins University, Baltimore, Md., and the Department of Physiology, University of Wisconsin, Madison, Wisc. In the past two decades the structure and connections of the thalamus have been extensively studied in various mammals. Although many findings are still fragmentary certain general conclusions seem justifiable. In the following account developmental, comparative-anatomical and experimental facts pertaining to the basic organization of the thalamus and its relations to the cerebral cortex in mammalian forms will be reviewed. The first important question to be considered is whether all thalamic nuclei can be proved to possess cortical connections, and if not, whether the nuclei independent of the cortex form a morphological subdivision definable in comprehensive anatomical terms. It has been known for a long time that certain thalamic nuclei, e.g., the habenular complex, remain intact after any lesion :of the endbrain. The exact determination, however, of all nuclei which are independent of the endbrain 1 is a problem difficult to attack experimentally, and even the recent literature contains a number of contradictory statements. Actually a close relation seems to exist between the site of the origin of a nucleus from its thalamic primordium and its dependence upon the cerebral cortex. A few development data will illustrate this. If one considers the thalamic plate in a rabbit embryo in early stages of development (figs. I-3) three distinct areas are apparent: a dorsal, designated as epithalamus (Ep), a middle, marked as dorsal thalamus ( T d ) , and a ventral, called ventral thalamus (Tv).

The most dorsal subdivision is larger posteriorly than anteriorly and fibers of Meynert's tract are apparent in its posterior sector. Figures 4-6 show sections from a later developmental stage. W i t h the epithalamus the anlagen of the habenular complex anteriorly and of the pretectal group of nuclei posteriorly are visible. The middle division is still undifferentiated. In the ventral thalamus the anlagen of the reticular complex (R) and of the ventral lateral geniculate body (Gev) are seen. Figures 7 and 8 show a still later stage of development. Within the epithalamus and ventral thalamus all the definiti,,e nuclei can be identified. Within the dorsal thalamus differentiation has just started. The whole area has become divided into several sectors and it is within these sectors that, at still later stages, definitive nuclei will become differentiated. If one traces the development of the thalamic nuclei through all stages (19) it can be shown that the habenular complex (medial and lateral habenular nuclei), the paraventricular complex (anterior and posterior paraventricular nuclei) and the pretectal group (anterior and posterior pretectal nuclei, medial pretectal area, nucleus of the optic tract and pretectal suprageniculate nucleus ~ the latter not to be confused with the suprageniculate nucleus of the dorsal thalamus) all originate in the epithalamus. All epithalamic nuclei share an important property in common: theq remain intact after complete removal of the endbrain in the rabbit (16, 20) and it appears 1By endbrain or telencephalon is meant all cor- safe to state that the same holds true for all tical structures (includin0 the rhinencephalon), the septal structures, striatum (putamen and caudate nu- other mammals since no other worker has cleus) and amygdaloid nucleus. ever reported degeneration of these ele[391]

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ments with a n y injuries to the endbrain in marsupials, carnivores and primates (2, 4, 6,

25). It thus a p p e a r s that in primitive forms the epithalamic nuclei are independent of the cortex and indeed of the whole endbrain and remain independent of it in all mammals, although their size in higher forms may be relatively greatly reduced. T h e wide-

the ventral thalamus. This area (Tv, figs. 1-3) constitutes in early stages of development a prominent sector fusing caudally with the dorsal hypothalamic area. T h e most important structures which arise in this sector are, as mentioned, the reticular complex (R) and the ventral lateral 9eniculate ( G e v ) , T h e ventral lateral ,qeniculate body is a puzzling structure. It is a large and amply

Figs. 1-3 Three frontal preparations throucjh the diencephalon of an 18mm. rabbit embryo, Figure 1 shows its oral figure 3 its caudal end. The thalamic plate is divisible into three embryonic areas, epithalamus (EpJ, dorsal thalamus (Td), and ventral thalamus (Tv) the bountaries of which are indicated by arrows. (E 30. sections 124, 151, and 185. 15p., x 301 Abbreviations to ficjures 1-8, ci, internal capsule; Ep, epithalamus; Gev, ventral lateral 9eniculate body; Ged, dorsal lateral geniculate body; H, habenular complex; Hc, central hypothalamic area: Hd dorsal hypothalamic area; M, mesencephalon; Par. paraventricular complex; pp, pes pedunculi; Pt. pretectal nuclear 9roup; R, reticular complex: rf, fasciculus retroflexus of Meyaert; Td, dorsal thalamus: Tv. ventral thalamus. spread belief that there is a progressive cortica[ization of thalamic nuclei in mammals is certainly not correct in regard to the epithalamus. It can be shown that this idea is equally untenable for the dorsal thalamie nuclei, since all of them degenerate after removal of the endbrain, even in the rabbit. Before considering the dorsal thalamus it is convenient to review the development of

differentiated complex in primitive forms. Its topographical situation ventral to the dorsal laterM geniculate body has suggested that it may be a primitive component of the thalamic visual system an idea reflected in its name, and seemingly supported by the fact that this complex remains intact after complete ablation of the endbrain and by the observation that it is smaller in higher

ORGANIZATION OF THALAMHS forms. H o w e v e r , no retinal fibers seem to terminate in it (3, 15) and its functional significance remains quite obscure. I m p o r t a n t experimental evidence is available in regard to the reticular complex. T h i s large nuclear complex originates at the junction of the thalamus with the endbrain and retains this position permanently. It is always intercalated as a sheath of cells between the internal capsule and the dorsal thalamus. Its reactions after cortical removals are remarkable. A f t e r various re-

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these exceptional findings in respect to the reticular complex and our experience in rabbit and cat corroborates his observations. It is not clear whether the reticular complex actually projects upon the entire cortex. T h e r e is little doubt, however, that in the rabbit it projects to a number of cortical fields to which dorsal thalamic nuclei also project. It appears reasonable to conclude, therefore, that different sectors of the reticular complex project upon different cortical fields and that the total projection system of

Figs. 4-6 Three frontal preparations through the diencephalon of a 33mm. rabbit embryo. Figure 4 shows its oral, figure 6 its caudal end. In the epithalamus the anlagen of the habenular complex (H) and the pretectal group (Pt) can be observed. In the ventral thalamus the reticular complex (R) and the complex of the ventral lateral geniculate (Gev) can be seen. Note the fusion of the ventral thalamus with the hypothalamic plate and note that the dorsal thalamus is not yet differentiated. (E 99, sections 215, 250, and 283, 15p., x 30.) stricted cortical removals changes are present within different restricted sectors of the reticular complex. In sharp contrast to the dorsal thalamic nuclei each of which degenerates throughout after a suitable restricted lesion to the endbrain, no restricted removal of the cortex seems sufficient to produce degeneration within the whole reticular system. Such degeneration can be achieved, however, if the entire endbrain is removed. Nissl (16) called attention to

this complex is comparable to the total projection system of the dorsal thalamus rather than to a n y portion of it, a conclusion which is in h a r m o n y with the fact of its different embryonic origin. T h e reticular complex is very well developed in all mammals. In primates it appears to be much less prominent than in the macrosmatic forms. This, howeever, is p r o b a b l y the result of the powerful development of the dorsal thalamus rather than an actual reduction of the reticular corn-

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plex. Although the functional significance of this complex is obscure it is important to stress that it represents the only known single thalamic complex which by virtue of its connections could activate a large number of cortical fields apparently independently of the dorsal thalamic systems. Figures 4-8 illustrate that the middle portion of the thalamic plate, which gives rise to the dorsal thalamus ( T d ) , is still largely undifferentiated at a time when the

clei), the medial 9roup (mediodorsal, medioventral, paratenial nuclei) and the midline and intralaminar complexes (nucleus rhomboidalis with its wing, nuclei centratis medialis, paracentralis, centralis lateralis). It is not clear whether the centrum medianum and the parafascicular nucleus belong to the midline and intralaminar system and whether the commissural nuclei of the anterior. medial and ventral groups are also components of this system. The,,, will be considered

Figs. 7 and 8 Two frontal preparations through the thalamus of a 50ram. rabbit embryo. Note the advanced differentiation of the epithalamic and ventral thalamic nuclei. The differentiation of the dorsal thalamus has just barely started. Because of the differences in time of development the separation of the epithalamicl dorsal thalamic and ventral thalamic nuclei is much simpler morphologically in an embryo than in the adult. (E 108, sections 236 and 267, 15~, x 30), definitive nuclei of epithatamus and ventral thalamus are already visible. In all mammals the dorsal thalamus gives rise to a large number of thalamic nuclei. T h e nuclear groups which originate in it are: the medial and dorsal lateral 9eniculate bodies, the ventral group (ventroanterior, ventromedial, ventrolateral nuclei, and ventrobasal complex), the dorsolateral group (lateral, posterior, and suprageniculate nuclei, pulvinar complex), the anterior group (anterodorsal, anteroventral and anteromedial nu-

as parts of this system, however, in further considerations. T h e late development of the dorsal thalamus, suggestive of its recent phylogenetic origin, is m harmony with the fact that all nuclei which oriainate from it. in contrast to the epithatamic nuclei, degenerate without exception after removal of the endbrain. Equally significant is the fact that each of these nuclei proiects onhl to a restricted area of the endbrain. Almost all modern authors are agreed that this undoubtedly is

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Fig. 9 Horizontal preparation through the ventral portion of the dorsal thalamus in a rabbit with a unilateral ablation of the endbrain. Note that practically no normal nerve cells are visible to the left of the midlinc and that all dorsal thalamic nuclei, including the midline and intralaminar nuclei, are degenerated throughout. ( R W I 9 , section 436, 20/~, x 30). Fi0. 10 Frontal preparation through the dorsal thalamus at the level o f the habenular nucleus in a rabbit with a unilateral ablation of the endbrain. Habenular and paraventricular nuclei are intact bilaterally. Note that in the dorsal thalamus there are hardly any normal cells left to the riqht of the midline. (RWIS, section 1052, 20/,t, x 30). CO, central gray; cm, nucleus centralis medialis; Hl, lateral habenular nucleus; Hm, medial habenular nucleus; Hyp, hypothalamus; imd, nucleus intermediodorsalis;Md, mediodorsal nucleus; Par, paraventricular complex: pc, paracentral nucleus; rf, fasciculus retroflexus of Meynert; rh, rhomboida~ nucleus; Va, ventroanterior nucleus; Vine, pars medialis of the ventrobasal complex.

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so with the large m a j o r i t y of the dorsal t h a lamic nuclei. H o w e v e r . it is g e n e r a l l y ass u m e d that the m i d l i n e a n d i n t r a l a m i n a r n u clei. as well as a few of the smaller nuclei u s u a l l y i n c l u d e d in the medial group, do not project u p o n the e n d b r a i n . T h i s belief arose from findin.q that the midline and, at least,

tamic n u c l e u s is i n d e p e n d e n t of the neocortex it does not project u p o n the e n d b r a i n . has led to the belief that the middle p o r t i o n of the m a m m a l i a n dorsal t h a l a m u s represents the " p a l e o t h a l a m u s " w i t h o u t e n d b r a i n c o n n e c t i o n s . It can be s h o w n that the midline a n d i n t r a l a m i n a r nuclei will de-

Fig. 11 Frontal prcparalion at the level ot the anterior end of the mediodorsal nucleus IMd) in a cat. Eor the description of the operation in this animal see text. Note that the midline and mtralaminar nuclei are severely degenerated oil the right side. The dorsal, smaller celled, rhomboidal di\'ision t rh} Is partiall'~ preserved ira the midline. Its wing, however, sweeping around the mediodorsal nucleus is severely degenerated The ventral, larger-celled, central division (cm) of the midline system is severel'!., deqenerated both at the midline and laterally. ICat 35M. section 896. 20#. x 30). Av, anteroventral nucleus: Par, paraventricular complex: pc, paracentral nucleus tt. taenia thalami: V ventral nuclear slroup the middle s e g m e n t s of the i n t r a l a m i n a r nuclei r e m a i n e s s e n t i a l l y u n c h a n g e d a f t e r a b l a t i o n of the neocortex. T h e a s s u m p t i o n that a m a m m a l u n i l a t e r a l l y d e p r i v e d of its neocortex is a h e m i d e c o r t i c a t e d p r e p a r a t i o n . t o g e t h e r with the p r e s u m p t i o n that if a tha-

g e n e r a t e in the same fashion as other dorsal thalamic e l e m e n t s if one removes not o n l y the neocortex but, in a d d i t i o n , the so-called r h i n e n c e p h a l o n a n d the s t r i a t u m a n d a m y g dala. F i g u r e 9 s h o w s in a h o r i z o n t a l prep a r a t i o n d e g e n e r a t i o n of the midline a n d

ORGANIZATION OF THALAMLIS intralaminar nuclei in a rabbit after such an operation. Fioure. 10 shows similar deoeneration in another rabbit in a frontal preparation. It will be noted that all dorsal thalamic nuclei have degenerated on one side in both animals and that the degeneration stops rather sharply along the midline. In both animals the epithalamic nuclei, i.e.. the paraventricular complex ( P a r ) , the habenula and the pretectal group (not shown in the figures) remained intact. It is not necessary to remove the entire endbrain to produce severe degeneration in the midline and intralaminar nuclei. Figure 11 shows a frontal preparation of a cat in which Dr. P. Bard removed the frontal end of the hemisphere on one side approximately as far back as the rostrum of corpus callosum. T h e rhinencephalic structures were entirely removed or damaged to the level of the chiasm. Striatum and septal structures were partly damaged in their most anterior portions. T h e hypothalamus was essentially uninjured although its anterolateral end was slightly damaged for a short distance. O n the other side a small lesion was placed in and near the rhinencephalon in front of the chiasm. T h e changes resulting from this lesion need not be discussed here. Although the rhinencephalic structures were by no means entirely removed figure 11 shows that severe degeneration is present in the anterior portion of the midline and intralaminar structures on the right side in addition to degenerations present in other dorsal thalamic nuclei which are known to project to the cortex removed. It is significant to point out that the lateral and posterior nuclei, the pulvmar, and the geniculate bodies were intact and some elements of the anterior and ventral groups were also partly preserved. T h e s e findings provide evidence that the midline and intralaminar nuclei not only project to the endbrain but also that they project only to restricted telencephalic areas. T h e exact identification of these areas. however, is a difficult problem since it is technically almost impossible to ablate the so-called rhinal cortex without partial damage to the septal structures, striatum and

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amygdala. For that reason it still remains to be determined whether the midline and intralaminar nuclei project upon the cortex or subcortical ganglia or both. Although the precise projection areas of these nuclei are not known, past experience indicates that only the anterior portion of the rhinencephalon receives thalamic projections. It appears likely that the entorhinal and pre~ subicula~: regions as well as Ammon's formation are not essential for the preservation of any thalamic element. It is of some importance to point out that the midline and intralaminar nuclei are not the only dorsal thalamic elements which project upon the so-called rhinencephalon. T h u s the paratenial nucleus, often assumed not to have endbrain connections, certainly projects upon it (23, 12, 20). T h e medioventral nucleus probably projects upon the infralimbic field (area 25 of B r o d m a n n ) , a field closely associated with the rhinencephalon (21). Finally, the centrum medianum, if it projects upon the cortex at all, is likely to project upon regions in the vicinity of the rhinal sulcus. T h e available evidence in regard to the dorsal thalamic nuclei may be summarized as follows: no dorsal thalamic nucleus is known to project upon widely separate portions of the endbrain and there is conclusive evidence that each will degenerate after restricted suitable removal of the telencephalon. If an essential projection field is defined as an endbrain area which on destruction causes a thalamic nucleus to degenerate, it can be stated that no overlap, or only minimal overlap," exists between the essential projection fields of the dorsal thalamic nuclei. It should be stressed that this statement implies that an essential projection area of one nucleus may receive projections from another nucleus if those fibers are collaterals only. T h e overwhelming majority of the dorsal thalamic nuclei is known to project upon the cortex. A small group may project upon the cortex, or subcortical .qanglia, or both. It is temptinq to consider that all dorsal thalamic nuclei depend on the cortex. This problem, however, appears rather aca-

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demic at present, since the nuclei in question All nuclei in these groups, although pro-project upon rhinal structures and w h a t bably already present in opossum and cerconstitutes cortex in these regions is often tainly in rat and rabbit, are only modestly a matter of definition. developed in these forms. T h e pulvinar in If the phyletic development of the dorsal particular is quite minute, All of them inthalamus is considered in a representative crease markedly in relative size in ungulates series of mammals, several general stateand carnivores, and in the primates their ments may be justifiably made. T h e r e are development and internal differentiation certain nuclear groups which remain relareaches remarkable proportions. All these tively stable; there are some which are denuclei are known to project upon the neoveloped well only in microsmatic mammals; cortex. and finally there are some which are best Quite the opposite occurs in phylogeny deve!oped in macrosmatic forms. T h e stable in the second series of intrinsic thalamic nunuclear groups are the dorsal lateral and clei. This series comprises the midline and medial geniculate bodies, the ventral group, most of the intralaminar nuclei, the medioand the anterior group. T h e y may be con- ventral element and the paratenial nucleus. sidered stable primarily because their overall W i t h o u t exception these nuclei are e x c e b development is excellent in all forms, although lently developed in macrosmatic forms and the relative development of nuclei within a undergo a strong reduction in the primates. group, as well as the internal differentiation T h e y project, as stated above, to or near of the nuclei may be very different in dif- rhinencephalic structures. A puzzling ex~ ferent species. T h e first three groups menception in this group is the centrum mediationed receive, as is well known, visual, au- num. It appears to develop (18, 7) from the ditory, and somatic afferent fibers. In adintralaminar system yet it is poorly developdition i~ is very likely that taste fibers ed in macrosmatic forms, becoming prominent only in primates. Its projection area is terminate within some elements conventionstill a matter of conjecture, but there is ally included in the ventral group (17) and certain ventral nuclei are known to receive little doubt that it does not project upon the cerebellar impulses. T h e anterior group re- neocortex. It seems justifiable to assume that the in~ ceives its main afferent impulses from the trinsic thalamic nuclei represent a higher mammillary configuration by w a y of the functional level than the extrinsic ones, since mammillo-thalamic tract. All these groups may be designated as extrinsic since all of their activity is presumably largely determined by the activity of the extrinsic systhem (and they alone of the thalamic nutems. If this is so, it would follow that clei) are known to receive a substantial portion of their afferent connections from extra- in respect to their thalamic connections cortical fields can be divided into at least two thalamic sources. It is of interest to note that all extrinsic thalamic nuclei are rela- and probably three types. T h e first type tively stable in mammals. A very different includes fields receiving projections from the situation prevails with all other dorsal tha- extrinsic thalamic nuclei. T h e s e fields will be lamic nuclei which will be designated as referred to as the primar!t projection areas. intrinsic, since it appears fair to assume that T h e y a p p e a r to be phylogenetically the a substantial portion of their afferent con- oldest among the neocortical fields. T h e nections originates within the thalamus it- second type are fields receiving projections from the intrinsic thalamic nuclei. T h e s e self. T h e intrinsic dorsal thalamic nuclei can be fields will be referred to as secondar~l projection areas. T h e third type may be cordivided into two series according to their tical fields which do not receive a n y thaphyletic development. T o the first series belong the mediodorsal nucleus, the lateral and lamic projections whatsoever. W h e t h e r such posterior nuclei and the pulvinar complex. athalamic fields actually exist cannot be

ORGANIZATION OF THALAMLIS answered satisfactorily by the retrograde degeneration method. Much experimental work is needed to clarify this problem. However, there is little doubt that there are cortical fields in mammals destruction of which causes no changes in the thalamus and thus it is reasonable to conclude that such fields at least do not receive essential or exclusive projections from the thalamus. In the rabbit, Ammon's formation and the entorhinal region may be athalamic. It is not certain that any neocortical areas in the rabbit lack projections from the dorsal thalamus. If such areas exist they are certainly small. On the other hand W a l k e r (25) has shown that in the monkey a considerable portion of the temporal lobe may be lacking thalamocortical connections. Since the development of the neocortex in primates appears to exceed very much the development of the thalamic nuclei which proiect to it is seems not unlikely that in apes and man quite a few neocortical fields will prove to be without thalamic projections and thus represent true "association" areas. From a consideration of the mammalian dorsal thalamus it might be expected that the neocortex of primitive macrosmatic mammals is composed largely of primary areas, since the intrinsic thalamic nuclei projecting to neocortex are only feebly developed. T h a t this indeed is so is shown by the extents of the visual, auditory and somatic sensory fields as they have been determined in different mammals by the evoked potential technique (13, 1, 29, 31, 26, 27, 30, 24, 28). Figure 12 shows the extent of these fields in the rabbit. It will be noted that the visual, auditory and somatic sensory areas alone constitute the bulk of the neocortex. If it is considered that practically the entire medial hemispheric wall and a part of the dorsal surface as well constitute the limbic cortex receiving proiections from the anterior group of nuclei (21) and that a part of the motor area is likely to be the projection area of some elements of the ventral group, it is apparent that an overwhelming proportion of the neocortex and limbic cortex must be

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receiving projections from the extrinsic thalamic nuclei and thus must consist of primary receiving fields. T h e primary taste area is not shown in the figure. Available evidence (5, 10) suggests that it lies in or near the insular cortex. Figure 12 makes it clear that if the taste area is represented in the neocortex there is hardly any other place where it could be located. It will be noted that the rabbit possesses well developed ~econd visual and second somatic sensory areas (cross-hatched). T h e r e is little doubt that the second auditory field lies ventrally to the first area although the precise limits of this area are as yet undetermined. It is certain that the first visual, auditory, and somatic sensory fields, as defined by the method of recording evoked potentials, receive projections from the extrinsic thalamic nuc!ei and are thus primary areas. W e do not know, however, whether the second systems belonq to the primary or to the secondary fields as they are defined in this paper. Our experience thus far indicates that isolated lesions in the second auditory field of the cat do not produce degenerations in the thalamus. T h e experience of Dr. ]. M. Thompson (personal communication) has been similar in regard to the second visual aiea of the rabbit. This may mean that the cecond areas, if they possess a collateral projection from the intrinsic thalamic nuclei, are actually secondary fields. T h e possibility exists, however, that second fields may receive either a sparse projection from the extrinsic nuclei (which remained thus far undetected) or collateral projections from them. Under these conditions the second areas would constitute special subdivisions of the primary fields. Apart from the second potential fields. c]assification of which is not yet clear, the only cortex which can be devo:ed to other than primary functions in the rabbit is represented by rather minute strips. Some of these strips have been identified as projection areas of the intrinsic thalamic nuclei. T h u s the small orbitofrontal region is the essential projection area of the mediodorsal

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nucleus ( 2 2 ) . W e also h a v e e v i d e n c e that the strips i n t e r c a l a t e d b e t w e e n the v i s u a l area a n d the limbic c o r t e x a n d b e t w e e n the somatic s e n s o r y a n d v i s u a l a r e a s r e c e iv e pro}ections from the intrinsic t h a l a m i c nuclei.

fields. In the ary projection (if e x i s t e n t ) primary areas fields s h o u l d

m a c a q u e (fig. 14) the s e c o n & a r e a s a n d the a t h a l a m i c fields are d e f i n i t e l y l a r g e r than the ( e v e n if the s e c o n d p o t e n t i a l b e l o n g to t h e m ) . F i n a l l y , as

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Fios 12-14 Cortical fields of rabbit (12). cat (13) and monkey 414J Macaca mulatta . Black areas represent the motor fields as determined by electrical stimulation. H~tched areas snow the extent of the first visual. somatic sensory, and auditory fields as determined by the evoked potential method. The lateral margin of the limbic cortex (hatched) which extends in the rabbit upon the dorsal surface is just visible in the diagram. Crosshatched areas show the second visual, somanc sensory, and auditory fields as defined by evoked potential method. The question mark after the label "'auditory If" indicates that the limits of this field in the rabbit are uncertain. Dashes in figure 12 delimit schematically the extent of the insular cortex above the rhinal sulcus. In the diagram of the monkey brain the Sylvian fissure is drawn apart to reveal the extent of the auditory and second somatic potential fields on its banks. The second visual field is not shown in figure 14 since its precise limits in the macaque are undetermined. In the cat (fig. 13) the a r e a s i n t e r c a l a t e d b e t w e e n the p r i m a r y fields a r e much l a r g e r t h a n in the rabbit, a n d t h e r e are entire g y n representing other than primary receiwng

is well k n o w n , in m an the total e x t e n t of the p r i m a r y visual, a u d i t o r y a n d s o m a t i c sens o r y fields is r e l a t i v e l y small a n d the total cortical s u r f a c e of these fields t o g e t h e r w i t h

ORGANIZATION OF THALAMUS the primary limbic fields and the primary motor area is probably less than 15 per cent of the total cortical surface. From these facts it appears that a very prominent feature of the phyletic development of the mammalian neocortex consists in the growth and differentiation of those sectors which are intercalated between the primary projection fields. Although not all primary fields seem to be separated from each other by such intercalated "non-primary" areas, those which are so separated, drift, so to speak, farther apart the more highly the cortex is developed. Thus the amount of cortex between the primary projection fields is likely to be an indication of the phyletic status of its owner. In contrast to the development in primates of these intrinsic thalamic nuclei which project upon the neocortex the stron.q reduction in microsmatic mammals of those intrinsic thalamic nuclei which project upon the rhinal structures suggests that the projection fields of the latter should be greatly reduced. Since the projection areas of these systems are only vaguely known any conclusions must, of necessity, be preliminary. However, the experimental evidence indicating that the midline and intralaminar nuclei project in general to the anterior portion of the rhinencephalon seems in good agreement with the fact that it is primarily (and probably solely) the anterior portion of the rhinencephalon which undergoes marked reduction in the primates. It appears likely that the midline and intralaminar nuclei function at the same level as other intrinsic thalamic systems and that they relay thalamic activity in the macrosmatic mammals to the so-called rhinencephalon. The existence of such a neural mechanism in the thalamus can hardly be surprising if one considers that in some macrosmatic mammals well over half of the surface of the endbrain consists of rhinencephalic structures. If this interpretation is correct certain experimental facts in regard to the midline and intralaminar systems require considera-

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tion. As is well known, Morison and Dempsey (14) and Dempsey and Morison (8, 9) obtained a generalized or "recruiting" response from stimulation of the midline and intralaminar nuclei which they interpreted as suggesting that these systems project in a diffuse manner upon the cortex. Recently Jasper and Droogleever-Fortuyn (11) observed a synchronous, bilateral, slow activity of the entire cerebral cortex of the cat on stimulation of the anterior'portion of midline and intralaminar nuclei, which they interpreted as an indication that this system represents a kind of a pacemaker mechanism capable of synchronizing activity of the entire cortex. Morison and Dempsey characterized the recruiting response as occurring. with a delay of 20-35 msec., over very large areas of the cortex. T h e y felt that the recruiting response can be shown to take place through other than dorsal thalamic pathways and that its generalization over the cortex cannot be accounted for by intracortical relays. As has been indicated above it is wellnigh impossible to assume that the midline nuclei project upon the neocortex at all. let alone upon the entire neocortex. This consideration is compatible with the long delay of the recruiting response observed by Morison and Dempsey and Jasper and Fortuyn. since the great latency of the response would preclude the utilization of a direct pathway to the neocortex from the midline structures (even if such direct connections existed). It appears reasonab!e to suggest, that if the long delay of the recruiting response is a result of intrathalamic relays, there is a system within the thalamus which fulfills the requirements postulated as necessary for this response. W e believe that this system may be the reticular complex of the ventral thalamus. Its generalized projection upon the cortex independent of the dorsal thalamic nuclei suggests that activity in this system could be expected to possess, except for the long delay, all other characteristics of the recruiting response. W h e t h e r the recruiting response is or is not the actual

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JERZY E. ROSE and CLINTON N XVOOLSEY

result of a c t i v i t y of the r e t i c u l a r complex it a p p e a r s that that p a r t i c u l a r c o m p l e x r e p r e sents the o n l y sin qle n e u r a l s y s t e m w i t h i n the t h a l a m u s w h i c h is, p r e s u m a b l y , c a p a b l e of d i r e c t l y evokin,q .qeneralized cortical activity. SUMMARY The available data concordantly suggest that the m a m m M i a n t h a l a m u s consists o1~ three divisions d i f f e r e n t from each o t h e r in their p h y l o g e n e t i c a n d o n t o g e n e t i c d e v e l o p ment, a n d in their r e l a t i o n s to the cortex, The epithalamus (paraventricular complex. h a b e n u l a r c o m p l e x , a n d the p r e t e c t a l ,qroup of nuclei) ix e n t i r e l y i n d e p e n d e n t of the e n d b r a i n in all m a m m a l s a n d u n d e r qoes a s t r o n q r e d u c t i o n in h i g h e r forms. T h e d o r s a l t h a l a m u s is e n t i r e l y d e p e n d e n t on the e n d b r a i n . E a c h n u c l e u s of this division has a r e s t r i c t e d p r o j e c t i o n u p o n the e n d b r a i n w i t h o u t which it c a n n o t survive, T h e d o r s a l t h a l a m i c nuclei are c l a s s i f i e d as extrinsic or intrinsic d e p e n d i n g on w h e t h e r or not the}" receive a s u b s t a n t i a l p o r t i o n of their a f f e r e n t s from e x t r a - t h a l a m i c sources. It can be s h o w n that the n e o c o r t e x of prim/t~ve m a m m a l s consists l a r q e l y of p r o j e c t i o n a r e a s of extrin':ic t h a l a m i c nuclei (ptqmary" cortical a r e a s ) , w h e r e a s in the n e o c o r t e x o~ h i g h e r forms the p r o j e c t i o n a r e a s I s e c o n d a r v cortical a r e a s ) of the intrinsic t h a l a m i c nuclei become d o m i n a n t , T h e intrinsic t h a lamic nuclei arc s e p a r a b l e into two g r o u p s . T h o s e p r o i e c t i n q upon the n e o c o r t e x b e c o m e d o m i n a n t in p r i m a t e s , w h e r e a s the intrinsic nuclei p r o j e c t i n 9 u p o n the r h i n e n c e p h M i c s t r u c t u r e s are. on the whole, best d e v e l o p e d in m a c r o s m a t i c m a m m a l s . T h e v e n t r a l t h a I a m u s consists of one s u b division ( v e n t r a l l a t e r a l ,qeniculate b o d y ) e n t i r e b : i n d e p e n d e n t of the e n d b r a i n , a n d of a second subdivision (reticular complex) w h i c h p r o j e c t s u p o n a l a r g e n u m b e r of cortical fields. T h e s p a r s e a n d g e n e r a l i z e d t h o u g h s p a t i M l y well or q a n i z e d ~ p r o j e c t i o n of the r e t i c u l a r c o m p l e x p r o v i d e s a s y s t e m a p p a r e n t l y i n d e p e n d e n t of the d o r s a l t h a lamic p r o j e c t i o n s a n d c a p a b l e , p r e s u m a b l y , of e v o k i n g ,qeneralized cortical activity.

REFERENCES 1. BA,~D, P, Studies on the cortical representation of somatic sensibility, Bull. N. Y, Acad. Med,. 1938. 585-607; Hart,. Lect., 1938, 33: 143-169. 2. Barn, P. and Rtocn, D. MeK. A study of fouc cats deprived of neocortex and additional por: tions of the forebrain. Bull, Johns Hopkins Hosp, 1937, 60: 73-147. 3. BObIAN, D. An experimental study of the optic tracts arid retinal projections of the Virqinia opossum, ]. romp. Neut., 1937, 66: 113-144. 4. BOr?IAN. D. Studies on the diencephalon of the Virginia opossum. Part III. The thalamo-cor tical projection. 1. Co'~p. Nenr, 1942, 77:525 575. 5. BREMER, F. Physioto.qie nerveuse de la mdStlca tion chez le chat et le lapin. Arch. Inter Ph9 ;iol,, 199.3, 31: 308-352. 6 BROUWER, B. Examen anatomique du systemc nerveux central des deux chats decrits par ], G. Dusser de Barenne. Arch. Necr[. Physi(;~', 1920. 4: 124-176, 7 CranK, \V. E. Lr Onos. The structure and con nections of the thalamus, Brain, 1939., 5 5 : 4 0 6 470. 8. DEMPSE¥. E W'. and MORISON, R. S. The production of rhythmically recurrent cortical pote~rials after localized thalamic stimulation. Amer. J. Phgsiol., 194'~. I35: 293400. 9 DEI~,tPSEY. E. W. and MORISON, R. S. The interaction of certain spontaneous and induced cortical potentials. Amer. ] PhpsioL. 1942, I:/5 301-308. lo. GE~EBTZOFF, M. A. Recherches oscilloqraphiques ct ;matomo-physiologiques sur les centres cortical et thalamique du ,qofit. Arch. Int, Physiol., 1941 5I: 199-2~0 l I J,"~SPER, H. H. and DI?()C~C,LEEVEI~-FOnTUYN, J Experime~ta] studies on the functional anatomy of petit real epilepsy. Res PubL Ass. here, ment Dis., 194'/, 26:252-271 i2. L,,sm EY. K. ThaIamocortical connections of the rat's brain, ]. Comp. Ncur,, 1941, 75: 67-121. !]. ~,'~ARSttALL,W. H., WOOLSEY, C. N. and BArn-,, P. Representation of tactile sensibility in the monkey's cortex as indicated by cortical potentials Amcr. ]. Physiol.. 193'/. 119: 372-373. 14 M()RIsON. R. S. and DE,'qSEY, E, Wr A study of thalamocortical relatior~s. Amer, [ Pt~#sioL 1949., 1i'5: 281-2q2. 1"3 NIcH'rt~R[.EtN, O, E. and OotosY, F. An e~ perimental study of optic connexions m the sheep 1. Anat., 1944, 78: 59-67. 16. NIssI, F. Die Grosshirnanteile des Kamnchens, Arch. Pstlchiat. Neruenkr., 1913, 52:867-953 17. P~,TTON, H. D., RUCH, T, C. and WAI,KER, A. [{. Experimental hypogeusia from Horsley-Clarkc lesions of the thalamus in Maraca mulatta. ] Neuroph#,*iol., 1944, 7: 171-t84. ¢8. R~ocH, D. MeN. Studies on the diencephalon oi Carnivora. III. Certain myelinated fiber con nections of the diencephalon of the do,q (Cani~ familiaris), cat (FeEs domestica), and aevisa ICrossarchus obscurus}. ], romp. Neur, 1931. 53: ?d0-388, I9. ROSE, ], E. The ontogenetic development of the rabbit's diencephalon. [. romp. Neut., 1942, 77: 61-120,

ORGANIZATION OF THALAMUS 20. Ros~, ]. E. and WOOLSEY, C. N. A study of thalamocortical connections in the rabbit. Bull. Johns Hopkins Hosp., 1948, 73: 65-128. 21. ROSE, I. E. and WOOLSEY, C. N. Structure and relations of limbic cortex and anterior thalamic

22.

23. 24.

25. 26.

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27. WOOLSEY, C. N. Additional observations on a

nuclei in rabbit and cat. ]. Comp. Neut., 1948, 89: 28. 279-3't8. ROSE, 1. E. and WOOLSEY, C. N. The orbitofrontal cortex and its connections with the mediodorsal nucleus in rabbit, sheep and cat. Res. Publ. Ass. nero. ment. Dis., 1948, 27: 210-232. 29. S'rOFFELS,]'. Organisation du thalamus et du cortex c~r~bral chez le lapin. ]. beige NeuroL Psyehiat., 1939, 39: 557-575. TALnOT, S. A., WOOLSEY,C. N. and THOMPSON, ]. M. Visual areas I and II of cerebral cortex of rabbit. Fed. Proc. Amer. Soc. Exp. Biol., 1946, 30. 5: 103. WALKER,A. E. The primate thalamus. Chicago Univ. Chicago Press, 1938, 321 pp. WOOLSEY, C. N. "Second" somatic receiving 31. areas in the cerebral cortex of cat, dog and monkey. Fed. Proc. Amer. Soc. Exp. Biol., 1943, 2: 55.

"second" somatic receivin 0 area in the cerebral cortex of the monkey. Fed. Proc. Amer. Soc. Exp. Biol., 1944, 3: 53. WOOLSHY,C. N. and FAIRMAN,D. Contralateral, ipsilateral and bilateral representation of cutaneous receptors in somatic areas I and II of the cerebral cortex of pig. sheep and other mammals. Surflery, 1946. 19: 684-702, WOOLSEY,C. N., MARSHALL,W. H. and BARD,P. Representation of cutaneous tactile sensibility in the cerebral cortex of the monkey as indicated by evoked potentials, Bull. Johns Hopkins Hosp., 1942, 70: 399-'t41. WOOLSEY,C. N. and WANt;, G.-H. Somatic sensory areas I and II of the cerebral cortex of the rabbit. Fed. Proc. Amer. Soc., Exp. Biol., 194& 4: 79. WOOLSEY,C. N. and WALZL, E. M. Topical projection of nerve fibers from local regions of the cochlea to the cerebral cortex of the cat. Bull. ]ohns Hopkins Hosp., 1942, 71: 315-344.

DISCUSSION: JAMES L. O'LEARY, St. Louis, Mo.

T h e growing curiosity about the functional role of the thalamus in the communication netw o r k s of the forebrain is obvious to all of you. In seeking the solution of m a n y of the problems which concern the electroencephalographer, it is our good fortune to possess an enviable knowledge of the structure of the thalamus. T h e p a p e r which you have just heard is an example of the m a n y efforts to systematize the nuclei of the thalamus and their cortical connections. O n e purpose of neuroanatomical study is to trace the progressive elaboration which takes place from the simple a r r a n g e m e n t s of nerve cells and axons found in small, generalized piscine and amphibian brains to that of man. T h e important investigations of the H e r r i c k - H u b e r - C r o s b y - K a p p e r s school of comparative neurologists did much to establish the nuclear antecedents of the diencephalon in sub-mammalian and simple m a m m a lian forms. T h e comparative neurologists, studying small, generalized brains, used Nissl, W e i g e r t , reduced silver and Golgi methods extensively. Similar studies were carried out upon the mammalian diencephalon. In addition, the methods of retrograde cell degeneration and Marchi degeneration were used to establish precise topical relations between

thalamus and cortex. R e t r o g r a d e degeneration is brought about by removin 9 a small area of cortex, thus destroyin 9 the termini of a closely associated cluster of thalamocortical axons; with time, cell shrinkage, removal and replacement by filial tissue occurs in a corresponding area of the nucleus of origin in the thalamus. Le Gros Clark and others have used Marchi degeneration to follow the course of thalamocortical axons subsequent to experimental lesions in the rat thalamus, and W a l k e r has used that method to identify the sites of thalamic termination of the lernniscus systems in primates. O c c a sionally, the method of transsynaptic de9eneration has also been used to provide significant information. It is most reliable when a group of thalamic cells is activated principally from one synaptic source. Early in the course of development of modern structural knowledge of the thalamus. Ramon y Cajal skillfully employed the Golgi method on small mammalian brains (mouse) to estabish the existence of axons arising in each of the principal cortical areas and terminating in the thalamic nuclei. His schematic illustration of the ascending and descending axons between the parietal cortex of the rodent and the ventral nucleus of its thalamus m a y be

404

]ERZY E. ROSE and CLINTON N. WOOLSEY

said to provide the earliest anatomical basis for the reverberatin 9 circuit discussed by modern authors. An anatomical problem of immediate importance to electrophysiologicaI progress is that of establishing a clear definition of the extent, cellular content, and connections of the thalamic reticular system. How diffusely is it represented in the medial and lateral regions of the dorsal thalamus ? In the medial region does it include more than the intralaminar nuclei ? W h a t are the anatomical characteristics of its thalamocortical connections which make possible the diffuse effects of local stimulation in changing the pattern of activity over wide areas of the cerebral cortex ? Finally. I would call attention to another anatomical problem pertinent to electrophysio]ogica] investigation which has not yet been exploited with sufficient thoroughness. It concerns the determination of the cell axes, the spatial distribution of dendrites, and the composition of the axona] plexuses in dae different thatamic nuclei of mammals corn-

monly used in experimental work. I n t e r p r e tation of electrical records of highly synchronized activity is much more difficult in the thalamus than on the forebrain surface, since we deal with a closely spaced aggregation of nuclei in a buried part havin 9 divergent paths to an extensive cortical surface. An immediate problem lies in assigning an exact nuclear origin in the thalamus for a highly synchronized potential activated from the cortical source. T h e usual types of recording (concentric needle, single critical electrode against a remote point, or bipolar recording between two electrodes in the thalamus) may be expected to yield different characters of results under the same conditions of activity. It is felt that when a sufficient knowled,qe of cell orientation, spatial distribution of dendrites, and type and composition of axonal plexuses become available, it will be possible to utilize potential field data to vastly improve the present possibilities for assigning to a thalamic potential an exact locus of or/gin.

Re[erence: RosE, ]. E. and WOOLSEY, C. N. Organiza ion of the mammaliaan thalamus and its relationship,~ to the cerebral cortex. EEG C/in. NeurophysioL, 19411, 1: 391-404.