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Projections of the nucleus and tracts of the stria terminalis following lesions at the level of the anterior commissure
EXPERIMENTAL
NEUROLOGY
Projections
(1976)
51,468-479
of the Nucleus
following
Lesions
and Tracts
of the Stria
at the Level of the Anterior
BLAIR H. TURNER AND MARGARET Department
Received
of Anatomy,
19,197s;
revision
received
Commissure
E. KNAPP l
Medical School, Howard Washington, D.C. 20059
November
Terminalis
University,
February
lo,1976
The projections of the stria terminalis were traced with the Fink-Heimer stain following lesions at the level of the anterior commissure. The precommissural stria terminalis is amygdalofugal only, and projects to the nucleus of the anterior commissure, the medial preoptic area, the ventral portion of the capsule surrounding the ventromedial nucleus, and to the area closely adjacent to the periventricular nucleus by way of the medial corticohypothalamic tract. The postcommissural stria terminalis is both amygdalofugal and amygdalopetal. Its hypothalamic projection is to the lateral preoptic area and the bed nucleus of the stria terminalis, and to the lateral hypothalamus by way of the lateral preoptic area. The amygdaloid projection is mainly to the basolateral nucleus, with fewer terminations to the basomedial nucleus and the area surrounding the central nucleus. The projections of the bed nucleus of the stria terminalis are quite similar to the postcommissural stria, except for an additional projection to the magnocellular paraventricular and dorsal periventricular nuclei by way of the lateral filiform tract. The commissural stria terminalis projects contralaterally to cells within its fiber bundle and the posterior limb of the anterior commissure.
INTRODUCTION The stria terminalis is a compact bundle of fibers consisting of several distinct components having diverse origins and terminations. Several recent papers have defined the hypothalamic projections in detail (3, 9, 10) using stains for degenerating nerve fibers. The results obtained were based mainly on animals sustaining amygdaloid lesions. 1 This research was supported in part by Grants NB-05273 to the Institute of Neurological Sciences, University of Pennsylvania, and IR03MH-19713 and 5ROIMH25495. The authors would like to thank Mrs. C. N. Liu for her patient instruction in using silver stains. 468 Copyright All rights
@ 1976 by Academic Press, of reproduction in any form
Inc. reserved.
STRIA
TERMINALIS
PROJECTIONS
469
The experiments to be described represent an attempt at a broad characterization of the amygdaloid-stria terminalis-hypothalamic relationship by studying the patterns of degeneration following small and relatively discrete lesions of the different components of the stria and its bed nucleus at the level of the anterior commissure. Here, both amygdalofugal and amygdalopetal pathways can be described, in addition to the projections of the bed nucleus of the stria terminalis, which have not been reported previously. An additional reason for choosing this lesion site is the apparent paradox that destruction of the stria terminalis and its bed nucleus at the level of the anterior commissure results in hyperreactivity (14, 15), whereas the opposite effect is seen after amygdaloid lesions (19). A possible explanation might be that the two sites are, in terms of their projections, not equivalent anatomically. The bed nucleus of the stria terminalis of the rat has a diameter of approximately 1 mm in all planes and contains, in addition to cell bodies, three compact bundles of fibers : the precommissural stria terminalis, which is dorsal and medial in the bed ; the postcommissural stria, which forms the posterior, lateral border of the bed ; and the commissural stria terminalis, which divides the bed into dorsal, and ventral halves. Because of this spatial separation of its major components, it proved possible to lesion separately the precommissural stria, postcommissural stria, and bed nucleus. The Fink-Heimer stain was the method of choice because the pathways of fibers tracts as well as the projections of cell bodies were to be traced. Preliminary results of these experiments have been previously reported (16). MATERIALS
AND
METHODS
This report is based on the brains of 25 male Long-Evans rats which sustained unilateral damage to neural structures at the level of the anterior commissure. Of these, 10 had lesions confined to one or the other of the components of the stria terminalis. The others, with lesions of the caudateputamen, septum, nonstrial anterior commissure, fornix, or medial forebrain bundle, served as controls. Thin (300 pm) stainless-steel needles, insulated with epoxy except for the tip, were introduced stereotaxically into the brain at an angle (15” from the vertical) calculated to avoid the septum. Direct current was passed to produce the lesions. Three to 6 days later, the rats were deeply anesthetized and perfused with isotonic saline, then 10% formol-saline. The brains were stored in formol-saline and then for 2 or 3 days in 30% sucrose solution. Brains were cut in the coronal plane on a freezing microtome at 30 pm, and stored in formol-saline. The sections were stained using the Fink-Heimer technique, Procedure I (5).
470
TURNER
AND
KNAPP
RESULTS The description of the pattern of degeneration following strial lesions will be divided into three parts, each one centering on a different component of the stria terminalis. In none of the cases described below did the electrode impinge on the septum or fimbria. Precowwnissural Stria Terminalis. A lesion limited to this fiber bundle (Figs. 1 and 4) results in degeneration in two pathways. A small fiber system, the medial corticohypothalamic tract, can be traced going medially
FIG.
1. Projectionsof the precommissural stria terminalis.Degeneratingparticles
thought to be fibers are represented by dashes, those thought to be terminals by dots. Sections A through K are from one brain; A’ through c’ are from a different brain. The blackened area is the lesion. Abbreviations for all figures: bst-Bed nucleus of stria terminalis, ac-anterior commissure, po-preoptic area, f-fornix, ah-anterior hypothalamus, vmh-ventromedial nucleus of the hypothalamus, gp-globus pallidusputamen, St-tract of the stria terminalis, hl-lateral hypothalamus, ic-internal capsule, c, bl, bm-central, basolateral, and basomedial nuclei of the amygdala, fmmagnocellular part of the paraventricular nucleus, hpv-periventricular nucleus, lpolateral preoptic area, s-septum. Note that the precommissural stria terminalis and the medial corticohypothalamic tracts separate at the lesion site (D). Posteriorly, they again converge (H), with the medial corticohypothalmic tract appearing to terminate at this level in the periventricular region, whereas the precommissural stria terminalis continues caudally.
STRIA
FIG.
2. Projections
TERMINALIS
of the commissural
471
PROJECTIONS
and postcommissural
stria
terminalis.
from the lesion toward the fornix (Fig. lC-D; Fig. 4B, C). It moves dorsally and medially around the fornix (Fig. 4C) and then travels posteriorly in a position midway between the fornix and the third ventricle. The fibers move farther medially and ventrally in the region of the anterior hypothalamus, and terminate at that level closely adjacent to the periventricular nucleus. The second and larger projection proceeds medially and anteriorly from the lesion until the anterior border of the anterior commissure is reached, where the degeneration turns ventral and reverses its direction (Fig. 4A), now going posterior and increasingIy ventral throughout the medial preoptic and anterior hypothalamus (Fig. 1). In the posterior portion of the anterior hypothalamus, the bundle suddenly fans out and then immediately descends to the ventral part of the capsule surrounding the ventro-medial nucleus. In one brain, the final degeneration was limited to the ventromedial part of this capsule (Fig. 11-K), and in another animal sustaining a precommissural lesion somewhat posterior and lateral to the first, the terminations included both ventromedial and ventrolateral porI n addition, it is likely that the pretions of the capsule (Fig. IA’-C’). commissural stria terminalis gives off terminations to the nucleus of the anterior commissure and the medial preoptic area, because in one brain (not shown), with a lesion of this bundle in its most rostra1 position in the bed nucleus, terminal degeneration was limited to these structures and was not observed in the anterior hypothalamus or ventromedial nucleus.
TURNER
AND
KNAPP
/
I
FIG.
3. Projections
of the bed nucleus of the stria terminalis.
Commissural and Postcommissural Stria Terminalis. Lesions placed at the far lateral border of the nucleus of the stria terminalis (Figs. 2, 5A) resulted in degeneration of the commissural and postcommissural bundles. The bed nucleus and precommissural stria terminalis, and the posterior limb of the anterior commissure, were not damaged. The commissural component ‘crossesthe anterior commissure at this level, and bifurcates on the opposite side. One branch moves dorsolaterally in the nucleus of the stria terminalis-apparently without terminating there-and then ascends in the main tract of the stria. Degeneration becomes sparse as the stria travels posteriorly, ending by midcourse. The other component of the commissural stria terminalis follows the posterior limb of the contralateral anterior commissure and terminates in the region of the external capsule and claustrum. A large portion of the postcommissural stria terminalia terminates around the site of the lesion. Fine, dense, degeneration can be seen in the lateral part of the nucleus of the stria terminalis and in the dorsolateral lateral preoptic region. In addition, a moderate quantity of fibers proceed posteriorly in this region, occupying a dorsolateral position in the medial forebrain bundle. These fibers progressively thin out, the last being seen in the far lateral part of the lateral hypothalamus. The postcommissural stria terminalis also contains fibers afferent to the amygdala. They travel the entire length of the stria, occupying a
STRIA
TERMINALIS
PROJECTIONS
473
FIG. 4. A: The precommissural stria terminalis as it moves anteriorly from the lesion (top arrow) and as it moves posteriorly (bottom arrow) after reversing its course in front of the anterior commissure. B: Site of lesion (hollow arrow) producing degeneration in the precommissural stria terminalis and medial cortico-hypothalamic tract. Note the medial direction which this latter tract takes. C: The medial cortico-hypothalamic tract at a level slightly posterior to B. Degeneration is shown by arrow, and its position is indicated by the inset. D: Terminal and paraterminal degeneration of the precommissural stria terminalis in the ventromedial capsule of the ventromedial nucleus.
ventrolateral position in that bundle as they move caudally. Posteriorly, the postcommissural fibers turn ventral and terminate heavily throughout the posterior portion of the basolateral nucleus of the amygdala, and lightly
FIG. 5. A: Site of lesion (hollow arrow) of the postcommissural stria terminalis. Degenerating fibers can be observed going dorsally to become part of the amygdalopetal stria, and ventrally to end in the lateral preoptic region. B: Degeneration within, but mostly surrounding the central amygdaloid nucleus, following lesionin A. C : Lesion in bed nucleus of the stria terminalis (hollow arrow). D : Posteriorly directed degeneration (arrow) after lesion in C. Note that the fibers tend to travel in discrete fascicles, possibly as part of the medial forebrain bundle.
in the lateral part of the basomedial nucleus. Few, if any, terminals are seenwithin the central nucleus, but a moderate number are seen surrounding it. (Fig. SB). Bed Nucleus of the Stria Terminalis. Lesions were made which destroyed moderate portions of the nucleus of the stria terminalis; there was no involvement of the precommissural stria, but possibly slight damage to the postcommissural stria (Figs. 3, SC). The commissural stria terminalis was damaged more heavily (not shown). Terminal degeneration was dense in the immediate locale of the lesion, but was not observed in the more anterior, undamaged part of the nucleus. Two bundles of degeneration
STRIA
TERMINALIS
PROJECTIONS
475
leave the lesion area. One ascends in the main tract of the stria terminalis and travels back to the amygdala, terminating in the posterior part of the basolateral nucleus. The other bundle travels posteriorly from the lesion in the dorsolateral lateral preoptic area, probably as part of the medial forebrain bundle (Fig. SD). Part of this projection continues caudally with final terminations at the posterior level of the lateral hypothalamus. Another fiber bundle leaves the lateral hypothalamus at midlevel and turns medially as the lateral filiform tract and ends in the magnocellular division of the paraventricular nucleus and the dorsal half of the periventricular nucleus. DISCUSSION The pattern of degeneration following lesions of the various components of the stria terminalis at the level of the anterior commissure generally confirms the results of other workers who, making amygdaloid lesions, have traced the amygdalofugal fibers in the rat. However, by studying the stria terminalis at this level we have been able to add to this picture by describing the amygdalopetal component of the stria, the projections of the bed nucleus, a connection between the postcommissural stria terminalis and the lateral hypothalamus, and a stria terminalis contribution to the medial corticohypothalamic tract. Precommissural Stria Terminalis. This group of fibers is shown, in the present study, to contain only efferents of the amygdala. The cells of origin are in the posterior cortical amygdaloid nucleus (9) and probably receive since the anterior cortical amygdaloid nucleus olfactory information, receives a direct projection from the olfactory bulb (11). De Olmos and Ingram (10) have shown that the amygdala, via the precommissural stria terminalis, projects heavily to the anteromedial bed nucleus of the stria, the rostra1 bed nucleus of the anterior commissure, and contralaterally to the bed nucleus of the stria terminalis and the cortical amygdaloid nucleus. Following our precommissural stria lesions which were anterior and medial to those of De Olmos, we saw degeneration only in the anteromedial bed nucleus of the stria terminalis and the nucleus of the anterior commissure. De Olmos described a parolfactory radiation coming from the precommissural stria terminalis, but we did not see this, again possibly because of a difference in lesion placement. We did see relatively profuse particles, possibly degeneration products, in the basal part of the medial and lateral septum. However, these particles were quite dissimilar to all other degeneration seen in the stria terminalis system : they were bilateral, it was not possible to visualize the route the fibers took from the lesion, and degeneration was equally dense after precommissural, postcommissural, or medial forebrain bundle lesions. For these reasons, we feel a septal pro-
476
TURNER
AND
KNAPP
jection should be interpreted cautiously until another method, such as autoradiography, provides confirmation. After the precommissural stria terminalis reverses its ,direction in front of the anterior commissure, this compact bundle gradually descends in the medial preoptic area as it proceeds caudally, sending terminals to the closely surrounding area as it travels. This was also observed by Heimer and Nauta (6) and by De Olmos and Ingram (10). In the anterior hypothalamus, the bundle suddenly diffuses and descends to the ventral part of the capsule surrounding the ventromedial nucleus. It is interesting that in one brain the final degeneration was limited to the ventromedial part of the capsule, while in another it included both the ventromedial and ventrolateral capsule. Krieg (8) noticed a medial and lateral subdivision of the ventromedial nucleus. The present data suggest topographically different projections to these divisions. Degeneration in the medial corticohypothalamic tract was seen in the present experiments whenever lesions were made in the precommissural stria terminalis. The electrode needle did not touch the septum or fimbria. The fibers took the course, after turning medially from the lesion, described by other authors (12) and were traced to the lateral border of the periventricular nucleus. Raisman et al. (12) presented evidence that this tract originates in the subiculum. However, lesions of the subiculum would most likely also injure the cortical amygdaloid nucleus, because these two structures are closely adherent at the most posterior level of the amygdala (1). Further information is needed as to whether this tract originates solely in the amygdala, or in both amygdala and subiculum. Colnnzissural Stria Terminalis. The origin of this bundle, according to van Alphen (18), is in the nucleus of the lateral olfactory tract and the bed nucleus of the stria terminalis. In the present case, these fibers were observed, after crossing, to bifurcate. One branch goes dorsally to join the stria and then progressively thins out posteriorly, apparently terminating on the cells intermingling in the tract. This is in agreement with other studies using the Fink-Heimer stain (9, 18). De Olmos and Ingram (lo), using a cupric-silver stain, traced these fibers to the medial and lateral amygdaloid nuclei. The other branch moves ventrally in the posterior limb of the anterior commissure after crossing, apparently ending on cells surrounding this limb. This is in agreement iyith De Olmos, who also saw some endings in the lateral amygdaloid nucleus. Postcownissural Stria Terminalis. The present experiments show that this division of the stria terminalis contains both amygdalofugal and amygdalopetal fibers. The cells of origin of the amygdalofugal component are diverse, including the basal, central, and medial nuclei of the amygdala (9). The terminations are chiefly to the bed nucleus of the stria terminalis and its caudal continuation, where it merges with the lateral preoptic area.
STRIA
TERMINALIS
PROJECTIONS
477
No studies using amygdaloid lesions have indicated a later hypothalamic projection of the postcommissural stria terminalis. Therefore, it can be assumed that the lateral hypothalamic projection found in this study results from damage either to cells or fibers of passage in the most lateral part of the lateral preoptic area or the bed nucleus, which in turn project or were enroute to the lateral hypothalamus. It might be hypothesized that the postcommissural stria terminalis terminates on lateral preoptic cells which in turn project to the lateral hypothalamus, establishing a circuit between the amygdala and lateral hypothalamus. No degeneration was seen in the core of the ventromedial nucleus, or any other medial hypothalamic nuclei, after selective section of the postcommissural stria terminalis. The postcommissural stria terminalis also contains amygdalopetal fibers. Cowan et al. (3) showed evidence that these fibers originated in the rostra1 lateral hypothalamus, since more caudal lesions did not produce degeneration in the stria. However, Conrad et al. (2) describe amygdalopetal fibers in the stria which originate in the dorsal and median raphe nuclei. The experiments described in this paper indicate that the amygdalopetal stria terminalis fibers end mainly in the basolateral nucleus of the amygdala, with fewer terminations in the basomedial nucleus and around the central nucleus. The distribution of the amygdalopetal stria terminalis seen with the Golgi method is similar to that seen here; however, dendrites projecting transversely out from the central nucleus appear to receive a substantial number of these fibers (17). Cowan et al. (3) observed a much wider distribution, perhaps due to their larger hypothalamic lesions. The Bed Nucleus of the Striu Terminalis. There appears to be a topographical organization of amygdaloid afferents to the bed nucleus. Leonard and Scott (9) found an anterior-posterior organization, such that fibers from the basolateral nucleus end in the rostra1 bed nucleus of the stria terminalis, and those from the medial nucleus end ill the caudal part of the nucleus of the stria. Krettek and Price (7) found that the central, lateral, and basal nuclei project to the lateral bed nucleus, the caudal cortical and medial nuclei to the dorsomedial portion of the bed nucleus, and the rostra1 medial and basomedial nuclei to the central bed nucleus. The only other known afferents are from the thalamus, observed in the cat (17). Valverde has shown with the Golgi stain that some of the axons of the cells of the bed nucleus project locally to the preoptic region. Others project both to the preoptic region and to the stria terminalis, and still others, only to the latter. The amygdaloid degeneration found in the present experiments following bed nucleus lesions was not noticeably different from that seenwith postcommissural stria terminalis lesions. The lateral hypothalamic projection of the bed nucleus was also quite similar to that of the postcommissural stria terminalis, with an important exception. In this case, a small bundle of fibers leaves the lateral hypo-
478
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AND
KNAPP
thalamus and turns medially, becoming part of what appears to be the lateral filiform tract (8). Terminations appear to be principally in the magnocellular part of the paraventricular nucleus, and in the dorsal part of the periventricular nucleus. This is the first experimental description of a forebrain afferent system to the paraventricular nucleus. The stria terminalis is known to mediate aggressive and defensive behaviors (4). In addition, Stumpf (13) has observed that those nuclei in the amygdala and hypothalamus that are selectively sensitive to circulating estrogens, are connected by the stria terminalis. It can be specified further that these nuclei are interconnected only by the precommissural stria terminalis. Because it also receives olfactory input, the function of the precommissural stria may be to relay sexual, aggressive, and food-related olfactory cues to these amygdaloid and hypothalamic nuclei which sense internal needs. The function of the post’commissural stria terminalis, which connects nuclei that are not in primary receipt of olfactory or endocrine information, may be to use the information of the precommissural stria in organizing appropriate need-reducing behaviors. REFERENCES 1. BRODAL, A. 1947. The amygdaloid nucleus of the rat. J. Con@. Neural. 87: 1-16. 2. CONRAD, L. C. A., C. M. LEONARD, and D. W. PFAFF. 1974. Connections of the median and dorsal raphe nuclei in the rat: An autoradiographic and degeneration study. J. Camp. Neural. 156: 179-206. 3. COWAN, W. M., G. RAISMAN, and T. P. S. POWELL. 1965. The connexions of the amygdala. J. Neural. Neurosurg. Psychiat. 28: 137-151. 4. FERNANDEZ DE MOLINA, A., and R. W. HUNSPERGER. 1959. Central representation of affective reactions in forebrain and brain stem: Electrical stimulation of amygdala, stria terminalis, and adjacent structures. 1. Physiol. (London) 145: 251-265. 5. FINK, R. P., and L. HEIMER. 1967. Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res. 4: 369-374. 6. HEIMFZR, L., and W. J. H. NAUTA. 1969. The hypothalamic distribution of the stria terminalis in the rat. B&n Res. 13: 284-297. 7. KRETTEK, J. E., and J. L. PRICE. 1974. Connections of the amygdala with the bed nucleus of the stria terminalis and the hypothalamus in the rat and cat. Society for Neuroscience (Abstr) : 293. 8. KREIG, W. J. 1932. The hypothalamus of the albino rat. J. Camp. Netirol. 55: 19-89. 9. LEONARD, C., and J. SCOTT. 1971. Origin and distribution of the amygdalofugal pathways in the rat: An experimental neuroanatomical study. J. Comp. Neural. 141: 313-330. 10. DE OLMOS, J., and W. R. INGRAM. 1972. The projection field of the stria terminalis in the rat brain: An experimental study. J. Comp. Neztrol. 146: 303-334. 11. POWELL, T. P. S., W. M. COWAN, and G. RAISMAN. 1965. The central olfactory connexions. J. dnat. (London) 99: 791-F13.
STRIA
14.
15.
16. 17. 18.
19.
PROJECTIONS
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G., W. M. COWAN, and T. P. S. POF~ELL. 1966. An experimental of the efferent projection of the hippocampus. Bra& 89: 83-108. STUMPF, W. E. 1970. Estrogen-neurons and estrogen-neuron systems in the periventricular brain. Anz. J. dnat. 129: 207-218. THOMAS, B., and L. VAN ATTA. 1972. Hyperirritability, lever-press avoidance, and septal lesions in the albino rat. Pkyvsiol. Bclzazi. 8: 225-232. TURKER, B. H. 1970. Neural structures involved in the rage syndrome of the rat. J. Colfirp. Pllyvsiol. Psgchol. 71 : 103-113. TURNER, B. H. 1974. Projections of the nucleus and tracts of the rat stria terminalis. ilr~af. Rec. 178 : 479. VALVERDE, F. 1965. “Studies on the piriform lobe.” Harvard University Press, Cambridge. VAN ALPHEN, H. A. M. 1969. The anterior commissure of the rabbit. Actu Anat. (Suppl. 57) 74: l-112. WOODS, J. W. 1956. Taming of the wild norway rat by rhinencephalic lesions. Natwr. 178: 869.
12. RAISMAN, analysis
13.
TERMINALIS
NEUROLOGY
Projections
(1976)
51,468-479
of the Nucleus
following
Lesions
and Tracts
of the Stria
at the Level of the Anterior
BLAIR H. TURNER AND MARGARET Department
Received
of Anatomy,
19,197s;
revision
received
Commissure
E. KNAPP l
Medical School, Howard Washington, D.C. 20059
November
Terminalis
University,
February
lo,1976
The projections of the stria terminalis were traced with the Fink-Heimer stain following lesions at the level of the anterior commissure. The precommissural stria terminalis is amygdalofugal only, and projects to the nucleus of the anterior commissure, the medial preoptic area, the ventral portion of the capsule surrounding the ventromedial nucleus, and to the area closely adjacent to the periventricular nucleus by way of the medial corticohypothalamic tract. The postcommissural stria terminalis is both amygdalofugal and amygdalopetal. Its hypothalamic projection is to the lateral preoptic area and the bed nucleus of the stria terminalis, and to the lateral hypothalamus by way of the lateral preoptic area. The amygdaloid projection is mainly to the basolateral nucleus, with fewer terminations to the basomedial nucleus and the area surrounding the central nucleus. The projections of the bed nucleus of the stria terminalis are quite similar to the postcommissural stria, except for an additional projection to the magnocellular paraventricular and dorsal periventricular nuclei by way of the lateral filiform tract. The commissural stria terminalis projects contralaterally to cells within its fiber bundle and the posterior limb of the anterior commissure.
INTRODUCTION The stria terminalis is a compact bundle of fibers consisting of several distinct components having diverse origins and terminations. Several recent papers have defined the hypothalamic projections in detail (3, 9, 10) using stains for degenerating nerve fibers. The results obtained were based mainly on animals sustaining amygdaloid lesions. 1 This research was supported in part by Grants NB-05273 to the Institute of Neurological Sciences, University of Pennsylvania, and IR03MH-19713 and 5ROIMH25495. The authors would like to thank Mrs. C. N. Liu for her patient instruction in using silver stains. 468 Copyright All rights
@ 1976 by Academic Press, of reproduction in any form
Inc. reserved.
STRIA
TERMINALIS
PROJECTIONS
469
The experiments to be described represent an attempt at a broad characterization of the amygdaloid-stria terminalis-hypothalamic relationship by studying the patterns of degeneration following small and relatively discrete lesions of the different components of the stria and its bed nucleus at the level of the anterior commissure. Here, both amygdalofugal and amygdalopetal pathways can be described, in addition to the projections of the bed nucleus of the stria terminalis, which have not been reported previously. An additional reason for choosing this lesion site is the apparent paradox that destruction of the stria terminalis and its bed nucleus at the level of the anterior commissure results in hyperreactivity (14, 15), whereas the opposite effect is seen after amygdaloid lesions (19). A possible explanation might be that the two sites are, in terms of their projections, not equivalent anatomically. The bed nucleus of the stria terminalis of the rat has a diameter of approximately 1 mm in all planes and contains, in addition to cell bodies, three compact bundles of fibers : the precommissural stria terminalis, which is dorsal and medial in the bed ; the postcommissural stria, which forms the posterior, lateral border of the bed ; and the commissural stria terminalis, which divides the bed into dorsal, and ventral halves. Because of this spatial separation of its major components, it proved possible to lesion separately the precommissural stria, postcommissural stria, and bed nucleus. The Fink-Heimer stain was the method of choice because the pathways of fibers tracts as well as the projections of cell bodies were to be traced. Preliminary results of these experiments have been previously reported (16). MATERIALS
AND
METHODS
This report is based on the brains of 25 male Long-Evans rats which sustained unilateral damage to neural structures at the level of the anterior commissure. Of these, 10 had lesions confined to one or the other of the components of the stria terminalis. The others, with lesions of the caudateputamen, septum, nonstrial anterior commissure, fornix, or medial forebrain bundle, served as controls. Thin (300 pm) stainless-steel needles, insulated with epoxy except for the tip, were introduced stereotaxically into the brain at an angle (15” from the vertical) calculated to avoid the septum. Direct current was passed to produce the lesions. Three to 6 days later, the rats were deeply anesthetized and perfused with isotonic saline, then 10% formol-saline. The brains were stored in formol-saline and then for 2 or 3 days in 30% sucrose solution. Brains were cut in the coronal plane on a freezing microtome at 30 pm, and stored in formol-saline. The sections were stained using the Fink-Heimer technique, Procedure I (5).
470
TURNER
AND
KNAPP
RESULTS The description of the pattern of degeneration following strial lesions will be divided into three parts, each one centering on a different component of the stria terminalis. In none of the cases described below did the electrode impinge on the septum or fimbria. Precowwnissural Stria Terminalis. A lesion limited to this fiber bundle (Figs. 1 and 4) results in degeneration in two pathways. A small fiber system, the medial corticohypothalamic tract, can be traced going medially
FIG.
1. Projectionsof the precommissural stria terminalis.Degeneratingparticles
thought to be fibers are represented by dashes, those thought to be terminals by dots. Sections A through K are from one brain; A’ through c’ are from a different brain. The blackened area is the lesion. Abbreviations for all figures: bst-Bed nucleus of stria terminalis, ac-anterior commissure, po-preoptic area, f-fornix, ah-anterior hypothalamus, vmh-ventromedial nucleus of the hypothalamus, gp-globus pallidusputamen, St-tract of the stria terminalis, hl-lateral hypothalamus, ic-internal capsule, c, bl, bm-central, basolateral, and basomedial nuclei of the amygdala, fmmagnocellular part of the paraventricular nucleus, hpv-periventricular nucleus, lpolateral preoptic area, s-septum. Note that the precommissural stria terminalis and the medial corticohypothalamic tracts separate at the lesion site (D). Posteriorly, they again converge (H), with the medial corticohypothalmic tract appearing to terminate at this level in the periventricular region, whereas the precommissural stria terminalis continues caudally.
STRIA
FIG.
2. Projections
TERMINALIS
of the commissural
471
PROJECTIONS
and postcommissural
stria
terminalis.
from the lesion toward the fornix (Fig. lC-D; Fig. 4B, C). It moves dorsally and medially around the fornix (Fig. 4C) and then travels posteriorly in a position midway between the fornix and the third ventricle. The fibers move farther medially and ventrally in the region of the anterior hypothalamus, and terminate at that level closely adjacent to the periventricular nucleus. The second and larger projection proceeds medially and anteriorly from the lesion until the anterior border of the anterior commissure is reached, where the degeneration turns ventral and reverses its direction (Fig. 4A), now going posterior and increasingIy ventral throughout the medial preoptic and anterior hypothalamus (Fig. 1). In the posterior portion of the anterior hypothalamus, the bundle suddenly fans out and then immediately descends to the ventral part of the capsule surrounding the ventro-medial nucleus. In one brain, the final degeneration was limited to the ventromedial part of this capsule (Fig. 11-K), and in another animal sustaining a precommissural lesion somewhat posterior and lateral to the first, the terminations included both ventromedial and ventrolateral porI n addition, it is likely that the pretions of the capsule (Fig. IA’-C’). commissural stria terminalis gives off terminations to the nucleus of the anterior commissure and the medial preoptic area, because in one brain (not shown), with a lesion of this bundle in its most rostra1 position in the bed nucleus, terminal degeneration was limited to these structures and was not observed in the anterior hypothalamus or ventromedial nucleus.
TURNER
AND
KNAPP
/
I
FIG.
3. Projections
of the bed nucleus of the stria terminalis.
Commissural and Postcommissural Stria Terminalis. Lesions placed at the far lateral border of the nucleus of the stria terminalis (Figs. 2, 5A) resulted in degeneration of the commissural and postcommissural bundles. The bed nucleus and precommissural stria terminalis, and the posterior limb of the anterior commissure, were not damaged. The commissural component ‘crossesthe anterior commissure at this level, and bifurcates on the opposite side. One branch moves dorsolaterally in the nucleus of the stria terminalis-apparently without terminating there-and then ascends in the main tract of the stria. Degeneration becomes sparse as the stria travels posteriorly, ending by midcourse. The other component of the commissural stria terminalis follows the posterior limb of the contralateral anterior commissure and terminates in the region of the external capsule and claustrum. A large portion of the postcommissural stria terminalia terminates around the site of the lesion. Fine, dense, degeneration can be seen in the lateral part of the nucleus of the stria terminalis and in the dorsolateral lateral preoptic region. In addition, a moderate quantity of fibers proceed posteriorly in this region, occupying a dorsolateral position in the medial forebrain bundle. These fibers progressively thin out, the last being seen in the far lateral part of the lateral hypothalamus. The postcommissural stria terminalis also contains fibers afferent to the amygdala. They travel the entire length of the stria, occupying a
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FIG. 4. A: The precommissural stria terminalis as it moves anteriorly from the lesion (top arrow) and as it moves posteriorly (bottom arrow) after reversing its course in front of the anterior commissure. B: Site of lesion (hollow arrow) producing degeneration in the precommissural stria terminalis and medial cortico-hypothalamic tract. Note the medial direction which this latter tract takes. C: The medial cortico-hypothalamic tract at a level slightly posterior to B. Degeneration is shown by arrow, and its position is indicated by the inset. D: Terminal and paraterminal degeneration of the precommissural stria terminalis in the ventromedial capsule of the ventromedial nucleus.
ventrolateral position in that bundle as they move caudally. Posteriorly, the postcommissural fibers turn ventral and terminate heavily throughout the posterior portion of the basolateral nucleus of the amygdala, and lightly
FIG. 5. A: Site of lesion (hollow arrow) of the postcommissural stria terminalis. Degenerating fibers can be observed going dorsally to become part of the amygdalopetal stria, and ventrally to end in the lateral preoptic region. B: Degeneration within, but mostly surrounding the central amygdaloid nucleus, following lesionin A. C : Lesion in bed nucleus of the stria terminalis (hollow arrow). D : Posteriorly directed degeneration (arrow) after lesion in C. Note that the fibers tend to travel in discrete fascicles, possibly as part of the medial forebrain bundle.
in the lateral part of the basomedial nucleus. Few, if any, terminals are seenwithin the central nucleus, but a moderate number are seen surrounding it. (Fig. SB). Bed Nucleus of the Stria Terminalis. Lesions were made which destroyed moderate portions of the nucleus of the stria terminalis; there was no involvement of the precommissural stria, but possibly slight damage to the postcommissural stria (Figs. 3, SC). The commissural stria terminalis was damaged more heavily (not shown). Terminal degeneration was dense in the immediate locale of the lesion, but was not observed in the more anterior, undamaged part of the nucleus. Two bundles of degeneration
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leave the lesion area. One ascends in the main tract of the stria terminalis and travels back to the amygdala, terminating in the posterior part of the basolateral nucleus. The other bundle travels posteriorly from the lesion in the dorsolateral lateral preoptic area, probably as part of the medial forebrain bundle (Fig. SD). Part of this projection continues caudally with final terminations at the posterior level of the lateral hypothalamus. Another fiber bundle leaves the lateral hypothalamus at midlevel and turns medially as the lateral filiform tract and ends in the magnocellular division of the paraventricular nucleus and the dorsal half of the periventricular nucleus. DISCUSSION The pattern of degeneration following lesions of the various components of the stria terminalis at the level of the anterior commissure generally confirms the results of other workers who, making amygdaloid lesions, have traced the amygdalofugal fibers in the rat. However, by studying the stria terminalis at this level we have been able to add to this picture by describing the amygdalopetal component of the stria, the projections of the bed nucleus, a connection between the postcommissural stria terminalis and the lateral hypothalamus, and a stria terminalis contribution to the medial corticohypothalamic tract. Precommissural Stria Terminalis. This group of fibers is shown, in the present study, to contain only efferents of the amygdala. The cells of origin are in the posterior cortical amygdaloid nucleus (9) and probably receive since the anterior cortical amygdaloid nucleus olfactory information, receives a direct projection from the olfactory bulb (11). De Olmos and Ingram (10) have shown that the amygdala, via the precommissural stria terminalis, projects heavily to the anteromedial bed nucleus of the stria, the rostra1 bed nucleus of the anterior commissure, and contralaterally to the bed nucleus of the stria terminalis and the cortical amygdaloid nucleus. Following our precommissural stria lesions which were anterior and medial to those of De Olmos, we saw degeneration only in the anteromedial bed nucleus of the stria terminalis and the nucleus of the anterior commissure. De Olmos described a parolfactory radiation coming from the precommissural stria terminalis, but we did not see this, again possibly because of a difference in lesion placement. We did see relatively profuse particles, possibly degeneration products, in the basal part of the medial and lateral septum. However, these particles were quite dissimilar to all other degeneration seen in the stria terminalis system : they were bilateral, it was not possible to visualize the route the fibers took from the lesion, and degeneration was equally dense after precommissural, postcommissural, or medial forebrain bundle lesions. For these reasons, we feel a septal pro-
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jection should be interpreted cautiously until another method, such as autoradiography, provides confirmation. After the precommissural stria terminalis reverses its ,direction in front of the anterior commissure, this compact bundle gradually descends in the medial preoptic area as it proceeds caudally, sending terminals to the closely surrounding area as it travels. This was also observed by Heimer and Nauta (6) and by De Olmos and Ingram (10). In the anterior hypothalamus, the bundle suddenly diffuses and descends to the ventral part of the capsule surrounding the ventromedial nucleus. It is interesting that in one brain the final degeneration was limited to the ventromedial part of the capsule, while in another it included both the ventromedial and ventrolateral capsule. Krieg (8) noticed a medial and lateral subdivision of the ventromedial nucleus. The present data suggest topographically different projections to these divisions. Degeneration in the medial corticohypothalamic tract was seen in the present experiments whenever lesions were made in the precommissural stria terminalis. The electrode needle did not touch the septum or fimbria. The fibers took the course, after turning medially from the lesion, described by other authors (12) and were traced to the lateral border of the periventricular nucleus. Raisman et al. (12) presented evidence that this tract originates in the subiculum. However, lesions of the subiculum would most likely also injure the cortical amygdaloid nucleus, because these two structures are closely adherent at the most posterior level of the amygdala (1). Further information is needed as to whether this tract originates solely in the amygdala, or in both amygdala and subiculum. Colnnzissural Stria Terminalis. The origin of this bundle, according to van Alphen (18), is in the nucleus of the lateral olfactory tract and the bed nucleus of the stria terminalis. In the present case, these fibers were observed, after crossing, to bifurcate. One branch goes dorsally to join the stria and then progressively thins out posteriorly, apparently terminating on the cells intermingling in the tract. This is in agreement with other studies using the Fink-Heimer stain (9, 18). De Olmos and Ingram (lo), using a cupric-silver stain, traced these fibers to the medial and lateral amygdaloid nuclei. The other branch moves ventrally in the posterior limb of the anterior commissure after crossing, apparently ending on cells surrounding this limb. This is in agreement iyith De Olmos, who also saw some endings in the lateral amygdaloid nucleus. Postcownissural Stria Terminalis. The present experiments show that this division of the stria terminalis contains both amygdalofugal and amygdalopetal fibers. The cells of origin of the amygdalofugal component are diverse, including the basal, central, and medial nuclei of the amygdala (9). The terminations are chiefly to the bed nucleus of the stria terminalis and its caudal continuation, where it merges with the lateral preoptic area.
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No studies using amygdaloid lesions have indicated a later hypothalamic projection of the postcommissural stria terminalis. Therefore, it can be assumed that the lateral hypothalamic projection found in this study results from damage either to cells or fibers of passage in the most lateral part of the lateral preoptic area or the bed nucleus, which in turn project or were enroute to the lateral hypothalamus. It might be hypothesized that the postcommissural stria terminalis terminates on lateral preoptic cells which in turn project to the lateral hypothalamus, establishing a circuit between the amygdala and lateral hypothalamus. No degeneration was seen in the core of the ventromedial nucleus, or any other medial hypothalamic nuclei, after selective section of the postcommissural stria terminalis. The postcommissural stria terminalis also contains amygdalopetal fibers. Cowan et al. (3) showed evidence that these fibers originated in the rostra1 lateral hypothalamus, since more caudal lesions did not produce degeneration in the stria. However, Conrad et al. (2) describe amygdalopetal fibers in the stria which originate in the dorsal and median raphe nuclei. The experiments described in this paper indicate that the amygdalopetal stria terminalis fibers end mainly in the basolateral nucleus of the amygdala, with fewer terminations in the basomedial nucleus and around the central nucleus. The distribution of the amygdalopetal stria terminalis seen with the Golgi method is similar to that seen here; however, dendrites projecting transversely out from the central nucleus appear to receive a substantial number of these fibers (17). Cowan et al. (3) observed a much wider distribution, perhaps due to their larger hypothalamic lesions. The Bed Nucleus of the Striu Terminalis. There appears to be a topographical organization of amygdaloid afferents to the bed nucleus. Leonard and Scott (9) found an anterior-posterior organization, such that fibers from the basolateral nucleus end in the rostra1 bed nucleus of the stria terminalis, and those from the medial nucleus end ill the caudal part of the nucleus of the stria. Krettek and Price (7) found that the central, lateral, and basal nuclei project to the lateral bed nucleus, the caudal cortical and medial nuclei to the dorsomedial portion of the bed nucleus, and the rostra1 medial and basomedial nuclei to the central bed nucleus. The only other known afferents are from the thalamus, observed in the cat (17). Valverde has shown with the Golgi stain that some of the axons of the cells of the bed nucleus project locally to the preoptic region. Others project both to the preoptic region and to the stria terminalis, and still others, only to the latter. The amygdaloid degeneration found in the present experiments following bed nucleus lesions was not noticeably different from that seenwith postcommissural stria terminalis lesions. The lateral hypothalamic projection of the bed nucleus was also quite similar to that of the postcommissural stria terminalis, with an important exception. In this case, a small bundle of fibers leaves the lateral hypo-
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thalamus and turns medially, becoming part of what appears to be the lateral filiform tract (8). Terminations appear to be principally in the magnocellular part of the paraventricular nucleus, and in the dorsal part of the periventricular nucleus. This is the first experimental description of a forebrain afferent system to the paraventricular nucleus. The stria terminalis is known to mediate aggressive and defensive behaviors (4). In addition, Stumpf (13) has observed that those nuclei in the amygdala and hypothalamus that are selectively sensitive to circulating estrogens, are connected by the stria terminalis. It can be specified further that these nuclei are interconnected only by the precommissural stria terminalis. Because it also receives olfactory input, the function of the precommissural stria may be to relay sexual, aggressive, and food-related olfactory cues to these amygdaloid and hypothalamic nuclei which sense internal needs. The function of the post’commissural stria terminalis, which connects nuclei that are not in primary receipt of olfactory or endocrine information, may be to use the information of the precommissural stria in organizing appropriate need-reducing behaviors. REFERENCES 1. BRODAL, A. 1947. The amygdaloid nucleus of the rat. J. Con@. Neural. 87: 1-16. 2. CONRAD, L. C. A., C. M. LEONARD, and D. W. PFAFF. 1974. Connections of the median and dorsal raphe nuclei in the rat: An autoradiographic and degeneration study. J. Camp. Neural. 156: 179-206. 3. COWAN, W. M., G. RAISMAN, and T. P. S. POWELL. 1965. The connexions of the amygdala. J. Neural. Neurosurg. Psychiat. 28: 137-151. 4. FERNANDEZ DE MOLINA, A., and R. W. HUNSPERGER. 1959. Central representation of affective reactions in forebrain and brain stem: Electrical stimulation of amygdala, stria terminalis, and adjacent structures. 1. Physiol. (London) 145: 251-265. 5. FINK, R. P., and L. HEIMER. 1967. Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res. 4: 369-374. 6. HEIMFZR, L., and W. J. H. NAUTA. 1969. The hypothalamic distribution of the stria terminalis in the rat. B&n Res. 13: 284-297. 7. KRETTEK, J. E., and J. L. PRICE. 1974. Connections of the amygdala with the bed nucleus of the stria terminalis and the hypothalamus in the rat and cat. Society for Neuroscience (Abstr) : 293. 8. KREIG, W. J. 1932. The hypothalamus of the albino rat. J. Camp. Netirol. 55: 19-89. 9. LEONARD, C., and J. SCOTT. 1971. Origin and distribution of the amygdalofugal pathways in the rat: An experimental neuroanatomical study. J. Comp. Neural. 141: 313-330. 10. DE OLMOS, J., and W. R. INGRAM. 1972. The projection field of the stria terminalis in the rat brain: An experimental study. J. Comp. Neztrol. 146: 303-334. 11. POWELL, T. P. S., W. M. COWAN, and G. RAISMAN. 1965. The central olfactory connexions. J. dnat. (London) 99: 791-F13.
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16. 17. 18.
19.
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G., W. M. COWAN, and T. P. S. POF~ELL. 1966. An experimental of the efferent projection of the hippocampus. Bra& 89: 83-108. STUMPF, W. E. 1970. Estrogen-neurons and estrogen-neuron systems in the periventricular brain. Anz. J. dnat. 129: 207-218. THOMAS, B., and L. VAN ATTA. 1972. Hyperirritability, lever-press avoidance, and septal lesions in the albino rat. Pkyvsiol. Bclzazi. 8: 225-232. TURKER, B. H. 1970. Neural structures involved in the rage syndrome of the rat. J. Colfirp. Pllyvsiol. Psgchol. 71 : 103-113. TURNER, B. H. 1974. Projections of the nucleus and tracts of the rat stria terminalis. ilr~af. Rec. 178 : 479. VALVERDE, F. 1965. “Studies on the piriform lobe.” Harvard University Press, Cambridge. VAN ALPHEN, H. A. M. 1969. The anterior commissure of the rabbit. Actu Anat. (Suppl. 57) 74: l-112. WOODS, J. W. 1956. Taming of the wild norway rat by rhinencephalic lesions. Natwr. 178: 869.
12. RAISMAN, analysis
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