Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat.

The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis (BST), and rostral hypothalamus. In the present study we re-examined the projection of the ventral subiculum to these regions with the Phaseolus vulgaris leucoagglutinin (PHAL) method in the rat. The results confirm and extend earlier conclusions based primarily on the autoradiographic method. Projections from the ventral subiculum course either obliquely through the angular bundle to innervate the amygdala and adjacent parts of the temporal lobe, or follow the alveus and fimbria to the precommissural fornix and medial corticohypothalamic tract. The major amygdalar terminal field is centered in the posterior basomedial nucleus, while other structures that appear to be innervated include the piriformamygdaloid area, the posterior basolateral, posterior cortical, posterior, central, medial, and intercalated nuclei, and the nucleus of the lateral olfactory tract. Projections from the ventral subiculum reach the BST mainly by way of the precommissural fornix, and provide rather dense inputs to the anterodorsal area as well as the transverse and interfascicular nuclei. The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, "shell" of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary nucleus. We also observed a rather dense terminal field just dorsal to the suprachiasmatic nucleus that extends dorsally and caudally to fill the subparaventricular zone along the medial border of the anterior hypothalamic nucleus and ventrolateral border of the paraventricular nucleus. The general pattern of outputs to the hypothalamus and septum is strikingly similar for the ventral subiculum and suprachiasmatic nucleus, the endogenous circadian rhythm generator.     

Projections of the ventral premammillary nucleus.

The projections of the ventral premammillary nucleus (PMv) have been examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The results indicate that the nucleus gives rise to two major ascending pathways and a smaller descending pathway. One large ascending pathway terminates densely in most regions of the periventricular zone of the hypothalamus, with the notable exception of the suprachiasmatic, suprachiasmatic preoptic, and median preoptic nuclei. This pathway is in a position to influence directly many cell groups known to regulate anterior pituitary function. The second large pathway ascends through the medial zone of the hypothalamus and densely innervates the ventrolateral part of the ventromedial nucleus and adjacent basal parts of the lateral hypothalamic area, medial preoptic nucleus, principal nucleus of the bed nuclei of the stria terminalis, ventral lateral septal nucleus, posterodorsal part of the medial nucleus of the amygdala, posterior nucleus, and immediately adjacent regions of the posterior cortical nucleus of the amygdala. It is already known that these regions are major components of the sexually dimorphic circuit, and, interestingly, that they provide the major neural inputs to the PMv. The smaller descending projection from the PMv seems to innervate preferentially the posterior hypothalamic nucleus, although a small number of fibers appear to end in the tuberomammillary nucleus, supramammillary nucleus, specific regions of the medial mammillary nucleus, interfascicular nucleus, interpeduncular nucleus, periaqueductal gray, dorsal nucleus of the raphe, laterodorsal tegmental nucleus, Barrington's nucleus, and locus coeruleus. Relatively sparse terminal fields associated with ascending fibers were also observed in the dorsomedial nucleus of the hypothalamus; in the nucleus reuniens, parataenial nucleus, paraventricular nucleus of the thalamus, and mediodorsal nucleus; in the central nucleus of the amygdala, anterodorsal part of the medial nucleus of the amygdala, posterior part of the basomedial nucleus of the amygdala; and in the ventral subiculum and adjacent parts of hippocampal field CA1, and the infralimbic and prelimbic areas of the medial prefrontal cortex. Taken as a whole, the evidence suggests that the PMv receives two major inputs--one from the sexually dimorphic circuit, and the other from the blood in the form of gonadal steroid hormones--and gives rise to two major outputs: one (perhaps feed-forward) to the neuroendocrine (periventricular) zone of the hypothalamus, and the other (perhaps feed-back) to the sexually dimorphic circuit.     

Topography of projections from amygdala to bed nuclei of the stria terminalis

A collection of 125 PHAL experiments in the rat has been analyzed to characterize the organization of projections from each amygdalar cell group (except the nucleus of the lateral olfactory tract) to the bed nuclei of the stria terminalis, which surround the crossing of the anterior commissure. The results suggest three organizing principles of these connections. First, the central nucleus, and certain other amygdalar cell groups associated with the main olfactory system, innervate preferentially various parts of the lateral and medial halves of the bed nuclear anterior division, and these projections travel via both the stria terminalis and ansa peduncularis (ventral pathway). Second, in contrast, the medial nucleus, and the rest of the amygdalar cell groups associated with the accessory and main olfactory systems innervate preferentially the posterior division, and the medial half of the anterior division, of the bed nuclei. And third, the lateral and anterior basolateral nuclei of the amygdala (associated with the frontotemporal association cortical system) do not project significantly to the bed nuclei. For comparison, inputs to the bed nuclei from the ventral subiculum, infralimbic area, and endopiriform nucleus are also described. The functional significance of these projections is discussed with reference to what is known about the output of the bed nuclei.     

Afferent connections to the amygdaloid complex of the rat and cat: II. Afferents from the hypothalamus and the basal telencephalon

The projections from the basal telencephalon and hypothalamus to each nucleus of the amygdaloid complex of the rat, and to the central amygdala of the cat, were investigated by the use of retrograde transport of horseradish peroxidase (HRP). The enzyme was injected stereotaxically by microiontophoresis, using three different approaches. The ventral pallidum (Heimer, '78) and ventral part of the globus pallidus were found to project to the lateral and basolateral nuclei of the amygdala. The substantia innominata projects diffusely to the entire amygdaloid complex, except to the lateral nucleus and the caudal part of the medial nucleus. The anterior amygdaloid area shows a similar projection field, the only difference being that this structure does not project to any parts of the medial nucleus. The dorsal subdivision of the nucleus of the lateral olfactory tract sends fibers to the ipsilateral as well as the contralateral basolateral nucleus, and possibly to the ipsilateral basomedial and cortical amygdala. The ventral subdivision of the nucleus of the lateral olfactory tract was massively labeled after an injection in the ipsilateral central nucleus, but this injection affected the commissural component of the stria terminalis. The nucleus of the horizontal limb of the diagonal band of Broca connects with the medial, central, and anterior cortical nuclei, whereas the bed nucleus of stria terminalis and medial preoptic area are related to the medial nucleus predominantly. The lateral preoptic area is only weakly labeled after intra-amygdaloid HRP injections. The hypothalamo-amygdaloid projections terminate preponderantly in the medial part of the amygdaloid complex. Thus, axons from neurons in the area dorsal and medial to the paraventricular nucleus of the hypothalamus distribute to the medial nucleus and intra-amygdaloid part of the bed nucleus of stria terminalis. Most of the amygdalopetal fibers from the ventromedial, ventral premammillary, and arcuate nuclei of the hypothalamus end in the medial nucleus, but some extend into the central nucleus. A few fibers from the ventromedial nucleus of the hypothalamus reach the basolateral nucleus. The lateral hypothalamic area projects heavily to the central nucleus, and more sparsely to the medial and basolateral nuclei. The dorsal hypothalamic area and supramammillary nucleus show restricted projections to the central and basolateral nuclei, respectively. There are only a modest number of crossed hypothalamo-amygdaloid fibers. Most of these originate in the ventromedial nucleus of the hypothalamus and terminate in the contralateral medial nucleus. The projections from the basal telencephalon and hypothalamus to the central nucleus of the amygdala of the cat are similar to the corresponding projections in the rat.     

Organization of projections from the basomedial nucleus of the amygdala: A PHAL study in the rat

The organization of axonal projections from the basomedial nucleus of the amygdala (BMA) was examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The anterior and posterior parts of the BMA, recognized on cytoarchitectonic grounds, display very different projection patterns. Within the amygdala, the anterior basomedial nucleus (BMAa) heavily innervates the central, medial, and anterior cortical nuclei. In contrast, the posterior basomedial nucleus (BMAp) sends a dense projection to the lateral nucleus, and to restricted parts of the central and medial nuclei. Extra-amygdalar projections from the BMA are divided into ascending and descending components. The former end in the cerebral cortex, striatum, and septum. The BMAa mainly innervates olfactory (piriform, transitional) and insular areas, whereas the BMAp also innervates inferior temporal (perirhinal, ectorhinal) and medial prefrontal (infralimbic, prelimbic) areas and the hippocampal formation. Within the striatum, the BMAa densely innervates the striatal fundus, whereas the nucleus accumbens receives a heavy input from the BMAp. Both parts of the BMA send massive projections to distinct regions of the bed nuclei of the stria terminalis. Descending projections from the BMA end primarily in the hypothalamus. The BMAa sends a major input to the lateral hypothalamic area, whereas the BMAp innervates the ventromedial nucleus particularly heavily. Injections were also placed in the anterior cortical nucleus (COAa), a cell group superficially adjacent to the BMAa. PHAL-labeled axons from this cell group mainly ascend into the amygdala and olfactory areas, and descend into the thalamus and lateral hypothalamic area. Based on connections, the COAa and BMAa are part of the same functional system. The results suggest that cytoarchitectonically distinct anterior and posterior parts of the BMA are also hodologically distinct and form parts of distinct anatomical circuits probably involved in mediating different behaviors (for example, feeding and social behaviors vs. emotion-related learning, respectively). © 1996 Wiley-Liss, Inc.     

Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat

The efferent fiber connections of the nuclei of the amygdaloid complex with subcortical structures in the basal telencephalon, hypothalamus, midbrain, and pons have been studied in the rat and cat, using the autoradiographic method for tracing axonal connections. The cortical and thalamic projections of these nuclei have been described in previous papers (Krettek and Price, ′77b,c). Although the subcortical connections of the amygdaloid nuclei are widespread within the basal forebrain and brain stem, the projections of each nucleus have been found to be well defined, and distinct from those of the other amygdaloid nuclei. The basolateral amygdaloid nucleus projects heavily to the lateral division of the bed nucleus of the stria terminalis (BNST), to the caudal part of the substantia innominata, and to the ventral part of the corpus striatum (nucleus accumbens and ventral putamen) and the olfactory tubercle; it projects more lightly to the lateral hypothalamus. The central nucleus also projects to the lateral division of the BNST and the lateral hypothalamus, but in addition it sends fibers to the lateral part of the substantia nigra and the marginal nucleus of the brachium conjunctivum. The basomedial nucleus has projections to the ventral striatum and olfactory tubercle which are similar to those of the basolateral nucleus, but it also projects to the core of the ventromedial hypothalamic nucleus and the premammillary nucleus, and to a central zone of the BNST which overlaps the medial and lateral divisions. The medial nucleus also projects to the core of the ventromedial nucleus and the premammillary nucleus, but sends fibers to the medial division of the BNST and does not project to the ventral striatum. The posterior cortical nucleus projects to the premammillary nucleus and to the medial division of the BNST, but a projection from this nucleus to the ventromedial nucleus has not been demonstrated. Projections to the “shell” of the ventromedial nucleus have been found only from the ventral part of the subiculum and from a structure at the junction of the amygdala and the hippocampal formation, which has been termed the amygdalo-hippocampal area (AHA). The AHA also sends fibers to the medial part of the BNST and the premammillary nucleus. Virtually no subcortical projections outside the amygdala itself have been demonstrated from the lateral nucleus, or from the olfactory cortical areas around the amygdala (the anterior cortical nucleus, the periamygdaloid cortex, and the posterior prepiriform cortex). However, portions of the endopiriform nucleus deep to the prepiriform cortex project to the ventral putamen, and to the lateral hypothalamus.     

Amygdaloid efferents through the stria terminalis in the rat give origin to zinc-containing boutons

Many regions of the basal forebrain are innervated by zinc-containing axonal boutons. In the present work, the lesion/degeneration method, coupled with histochemical staining for zinc-containing boutons, was used to determine the origins and efferent pathways of these zinc-containing projections to the basal forebrain. Knife cuts of the stria terminalis or extensive electrolytic lesions of the amygdala resulted in the bleaching of the staining for zinc (Timm stain) and terminal degeneration (Fink-Heimer method) ipsilaterally in the following areas: granule cell layer of the accessory olfactory bulb, shell of nucleus accumbens, bed nucleus of the stria terminalis, striohypothalamic nucleus, retrochiasmatic area, ventromedial hypothalamic nucleus (in the cell-sparse shell), medial tuberal nucleus, terete hypothalamic nucleus, and ventral premammillary nucleus. Small lesions made with ibotenic acid in the posteromedial part of the amygdalohippocampal area caused bleaching of the stain for zinc in the accessory olfactory bulb, in the medial zone of the bed nucleus of the stria terminalis, and in the ventral premammillary nucleus. Lesions in either the ventral subiculum or the anterolateral part of the amygdalohippocampal area caused bleaching in the ventromedial hypothalamic nucleus. Lesions in the hippocampus or in the neocortex did not produce bleaching of the stain for zinc in the above-mentioned terminal fields. The present results agree with previous studies on amygdaloid efferents and suggest that neurons in the amygdalohippocampal area and, possibly, in the ventral subiculum give origin to zinc-containing boutons.     

Efferent connections of the basal forebrain in the cat: the substantia innominata

The efferent connections of the substantia innominata in the cat were studied with radioautographic methods. Injections of [³H]leucine were placed throughout the substantia innominata in 20 cats. The results indicate a complex organization to the efferent distribution of fibers from this region. The projections associated with more caudomedial regions of the substantia innominata resemble those of the adjacent preoptic-hypothalamic area and innervate the septal area, lateral habenular nucleus, and ventral tegmental area. Fibers arising from more caudolateral parts of the substantia innominata (ventral pallidum) appear to project in a crude topographic manner to the amygdala via two routes—the stria terminalis and a second group of caudolaterally directed axons. The fiber distribution from the region of the nucleus basalis is widespread to a variety of cortical sites, such as the olfactory bulb, prefrontal cortex, anterior cingulate gyrus, pyriform, and posterior sylvian cortices. Fibers arising from the rostral aspect of the substantia innominata adjacent to the nucleus accumbens are distributed exclusively to the ventral tegmental area and adjoining substantia nigra. All parts of the substantia innominata supply the ventral tegmental area.     

Efferent projections of the basolateral amygdala in the opossum, Didelphis virginiana

The autoradiographic anterograde axonal transport technique was used to study efferent projections of the opossum basolateral amygdala. All nuclei of the basolateral amygdala send topographically organized fibers to the bed nucleus of the stria terminalis (BST) via the stria terminalis (ST). Injections into rostrolateral portions of the basal nuclei label fibers that surround the commissural bundle of the ST, cross the midline by passing along the outer aspect of the anterior commissure, and terminate primarily in the contralateral BST, anterior subdivision of the basolateral nucleus (BLa), ventral putamen, and olfactory cortex. Each of the basal nuclei project ipsilaterally to the anterior amygdaloid area, substantia innominata and topographically to the ventral part of the striatum and adjacent olfactory tubercle. The posterior subdivision of the basolateral nucleus (BLp), but not the basomedial nucleus (BM), projects to the ventromedial hypothalamic nucleus. BLa and BLp have projections to the nucleus of the lateral olfactory tract and also send fibers to the central nucleus, as does the lateral nucleus (L). The lateral nucleus also has a strong projection to BM and both nuclei project to the amygdalo-hippocampal area. BLa and BLp send axons to the ventral subiculum and ventral lateral entorhinal area whereas L projects only to the latter area. The lateral nucleus and BLp project to the perirhinal cortex and the posterior agranular insular area. The BLa sends efferents to the anterior agranular insular area. Rostrally this projection is continuous with a projection to the entire frontal cortex located rostral and medial to the orbital sulcus. All of the nuclei of the basolateral amygdala project to areas on the medial wall of the frontal lobe that appear to correspond to the prelimbic and infralimbic areas of other mammals. Despite the great phylogenetic distance separating the opossum from placental mammals, the projections of the opossum basolateral amygdala are very similar to those seen in other mammals. The unique frontal projections of the opossum BLa to the dorsolateral prefrontal cortex appear to be related to the distinctive organization of the mediodorsal thalamic nucleus and prefrontal cortex in this species.     

The connections of the septal region in the rat

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.     

Organization of projections from the juxtacapsular nucleus of the BST: a PHAL study in the rat

The axonal projections of the juxtacapsular nucleus of the anterior division of the bed nuclei of the stria terminalis (BSTju) were examined with the Phaseolus vulgaris-leucoagglutinin (PHAL) method in the adult male rat. Our results indicate that the BSTju displays a relatively simple projection pattern. First, it densely innervates the medial central amygdalar nucleus and the subcommissural zone and caudal anterolateral area of the BST — cell groups involved in visceromotor responses. Second, it provides inputs to the ventromedial caudoputamen (CP) and anterior basolateral amygdalar nucleus — areas presumably modulating somatomotor outflow. Third, the BSTju sends dense projections to the caudal substantia innominata, a distinct caudal dorsolateral region of the compact part of the substantia nigra, and the adjacent mesencephalic reticular nucleus and retrorubral area. And fourth, the BSTju provides light inputs to the prelimbic, infralimbic, and ventral CA1 cortical areas; to the posterior basolateral, posterior basomedial, and lateral amygdalar nuclei; to the paraventricular and medial mediodorsal thalamic nuclei; to the subthalamic and parasubthalamic nuclei of the hypothalamus; and to the ventrolateral periaqueductal gray. These projections, in part, suggest a role for the BSTju in circuitry integrating autonomic responses with somatomotor activity in adaptive behaviors.     

The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat

Direct projections from the forebrain to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus in the rat medulla were mapped in detail using both retrograde axonal transport of the fluorescent tracer True Blue and anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). In the retrograde tracing studies, cell groups in the medial prefrontal cortex, lateral prefrontal cortex (primarily ventral and posterior agranular insular cortex), bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular, arcuate, and posterolateral areas of the hypothalamus were shown to project to the NTS and in some cases also to the dorsal motor nucleus of the vagus. The prefrontal cortical areas projecting to the NTS apparently overlap to a large degree with those cortical areas receiving mediodorsal thalamic and dopaminergic input. The retrogradely labeled cortical cells were situated in deep layers of the rat prefrontal cortex. The anterograde tracing studies revealed a prominent topography in the mediolateral termination pattern of forebrain projections to the rostral part of the NTS and to the dorsal pons. The projections to the NTS were generally bilateral, except for projections from the central nucleus of the amygdala and bed nucleus of the stria terminalis which were predominantly ipsilateral. The prefrontal cortical projections to the NTS travel through the cerebral peduncle and pyramidal tract and terminate throughout the rostrocaudal extent of the NTS. Specifically, the prefrontal cortex innervates dorsal portions of the NTS (lateral part of the dorsal division of the medial solitary nucleus, dorsal part of the lateral solitary nucleus and the caudal midline region of the commissural nucleus), areas which receive relatively sparse subcortical projections. These dorsal portions of the NTS receive major primary afferent projections from the vagal and glossopharyngeal nerves. In contrast, the subcortical projections, which travel through the midbrain and pontine tegmentum, terminate most heavily in the ventral portions of the NTS, i.e., the area immediately dorsal and lateral to the dorsal motor nucleus of the vagus. Only the paraventricular hypothalamic nucleus has substantial terminals throughout the dorsal motor nucleus of the vagus. Hypothalamic cell groups innervate the area postrema and, along with the prefrontal cortex, innervate the zone subjacent to the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)     

Projections from the subfornical region of the lateral hypothalamic area

The L-shaped anterior zone of the lateral hypothalamic area's subfornical region (LHAsfa) is delineated by a pontine nucleus incertus input. Functional evidence suggests that the subfornical region and nucleus incertus modulate foraging and defensive behaviors, although subfornical region connections are poorly understood. A high-resolution Phaseolus vulgaris-leucoagglutinin (PHAL) structural analysis is presented here of the LHAsfa neuron population's overall axonal projection pattern. The strongest LHAsfa targets are in the interbrain and cerebral hemisphere. The former include inputs to anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and ventral region of the dorsal premammillary nucleus (defensive behavior control system components), and to lateral habenula and dorsal region of the dorsal premammillary nucleus (foraging behavior control system components). The latter include massive inputs to lateral and medial septal nuclei (septo-hippocampal system components), and inputs to bed nuclei of the stria terminalis posterior division related to the defensive behavior system, intercalated amygdalar nucleus (projecting to central amygdalar nucleus), and posterior part of the basomedial amygdalar nucleus. LHAsfa vertical and horizontal limb basic projection patterns are similar, although each preferentially innervates certain terminal fields. Lateral hypothalamic area regions immediately medial, lateral, and caudal to the LHAsfa each generate quite distinct projection patterns. Combined with previous evidence that major sources of LHAsfa neural inputs include the parabrachial nucleus (nociceptive information), defensive and foraging behavior system components, and the septo-hippocampal system, the present results suggest that the LHAsfa helps match adaptive behavioral responses (either defensive or foraging) to current internal motivational status and external environmental conditions.     

Serotonin neurons of the midbrain raphe: ascending projections.

The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.     

Origin and distribution of the amygdalofugal pathways in the rat: an experimental neuroanatomical study

The fields of origin of the amygdalofugal pathways in the albino rat were studied by using the Fink-Heimer technique to stain degenerating fibers and terminals in brains of animals sacrificed four and seven days after small unilateral lesions of the amygdale. A surprisingly restricted field of origin was found for the supracommissural stria terminalis — the component projecting to the ventromedial nucleus of the hypothalamus Only a lesion in the most posterior part of the cortical nucleus produced degeneration in this pathway. The postcommissural stria terminalis which apparently distributes to the bed nucleus of the stria terminalis and preoptic area originates in a more widespread area including parts of both the basolateral and corticomedial complexes. Although intense terminal degeneration could be seen within the amygdala following all lesions, long fibers projecting into the anterior amygdaloid area, lateral preoptic area and lateral hypothalamus were found only after lesions in which fibers of passage from periamygdaloid cortex could have been interrupted. Convincing evidence, therefore, of a long axon ventral amygdalofugal pathway of the rat was not found in this study.     

The projection field of the stria terminalis in the rat brain. An experimental study

The problem of the stria terminalis projection field has been examined by use of two versions of the cupric-silver technique as well as variations of the Fink-Heimer and Nauta-Gygax techniques applied to material fixed under different conditions using brains from very young rats surviving 30 hours to four days after production of lesions at different levels of the course of the stria terminalis and related structures. The findings are as follows:

• (1) A dorsal subventricular portion of the stria terminalis divides into retrocommissural and supracommissural contingents which together account for degenerating terminals seen in the ipsilateral bed nuclei of the stria terminalis and of the anterior commissure, and in the medial preoptic-hypothalamic junction area. The supracommissural bundle also disseminates into the laterobasal septum, nucleus accumbens, olfactory tubercle, the posterior and medial divisions of the anterior olfactory nucleus, and the granular layer of the accessory olfactory bulb. Additional fibers end in the paucicellular capsule of the ventromedial hypothalamic nucleus, also in a small lateral parvocellular tuberal nuclear area, and throughout the premammillary nuclei. A small truly commissural division of the dorsal component was traced to the contralateral cortical amygdaloid nucleus and to small clusters of medial amygdaloid cells.
• (2) A ventral juxtacapsular portion of the stria terminalis was traced to the ipsilateral strial bed nucleus, medial preoptic-hypothalamic junction area, the entire ventromedial hypothalamic nucleus, the lateral tuberal area and the premammillary nuclei. The lateralmost fibers of the dorsal strial component as well as those of the ventral component which lie lateral to the “commissural bundle” appear to terminate exclusively in the lateral portions of the bed nucleus of the stria.
• (3) A “commissural bundle” or component, after crossing the midline in the anterior commissure, ends in the bed nucleus of the posterior limb of the latter, in the olfactory tubercle, prepiriform cortex, lateral amygdaloid nucleus and the strial bed nucleus. It is thus a decussation rather than a commissure. No contribution from stria terminalis to stria medullaris could be identified.

     

Histamine synthesizing afferents within the amygdaloid complex and bed nucleus of the stria terminalis of the rat.

The regional distribution of histidine decarboxylase (HD) activity has been studied in the amygdaloid complex and the bed nucleus of the stria terminalis (BST) of the rat. The central and medial nuclei of the amygdala had 2-fold higher HD activity levels than the remaining nuclei of the complex. HD activity was exceptionally high in the BST, particularly in its ventral part. A lesion of the stria terminalis had no effect on this distribution whereas a combined lesion of the stria terminalis and the so-called ventral pathway induced a decrease of approximately 60% in all the amygdaloid nuclei, but not in the BST. On the other hand, a lesion of the medial forebrain bundle (MFB) induced a similar decrease in both the amygdaloid nuclei and the BST. These results confirm that HD-containing fibres are present in the MFB. On the one hand these project massively to the BST and on the other penetrate in the amygdala ventromedially along the ansa peduncularis and preferentially innervate the more medially located nuclei.     

Supracapsular bed nucleus of the stria terminalis contains central and medial extended amygdala elements: evidence from anterograde and retrograde tracing experiments in the rat

Neurons that accompany the stria terminalis as it loops over the internal capsule have been termed collectively the supracapsular bed nucleus of the stria terminalis (BSTS). They form two cell columns, a lateral column and a considerably smaller medial column. The lateral column merges rostrally with the lateral bed nucleus of the stria terminalis and caudally with the central amygdaloid nucleus (central extended amygdala components). The medial column is continuous with the medial bed nucleus of the stria terminalis and the medial amygdaloid nucleus (medial extended amygdala districts). The connections of the BSTS were investigated in the rat by placing injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or retrograde tracers in different parts of the extended amygdala or in structures related to the extended amygdala. BSTS inputs and outputs were identified, respectively, by the presence of varicose fibers and retrogradely labeled neurons within the stria terminalis. The results suggest that the medial-to-lateral compartmentalization of BSTS neurons reflects their close alliance with the medial and central divisions of the extended amygdala. The medial BSTS contains primarily elements that correspond to the posterodorsal part of the medial amygdaloid nucleus and the medial column of the posterior division of the medial bed nucleus of the stria terminalis, and the lateral BSTS contains elements that correspond to the medial and lateral parts of the central amygdaloid nucleus and lateral bed nucleus of the stria terminalis. These results add strong support to the concept of the extended amygdala as a ring-like macrostructure around the internal capsule, and they are of theoretical interest for the understanding of the organization of the basal forebrain.     

Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex

Using cobalt-enhanced immunohistochemistry, the tracing of retrograde transport of horseradish peroxidase (HRP) and experimental manipulations, a widespread localization of corticotropin-releasing factor-like immunoreactive (CRFI) structures in the rat amygdaloid complex, and CRFI-containing pathways from the amygdala to the lower brainstem, bed nucleus of the stria terminalis (bst) and ventromedial nucleus of the hypothalamus (VMH) have been demonstrated. By means of cobalt-enhanced immunohistochemistry, CRFI cells were detected in almost all the regions of the amygdala, including the central amygdaloid nucleus (Ce), basolateral amygdaloid nucleus (B1), intra-amygdaloid bed nucleus of the stria terminalis (Abst), medial amygdaloid nucleus (Me), amygdalohippocampal area (Ahi), posterior cortical amygdaloid nucleus (Aco), lateral amygdaloid nucleus (La), anterior amygdaloid area (AAA) and basomedial amygdaloid nucleus (Bm). Neural processes with CRFI were found in all of the above areas. The greatest density of CRFI fibres was observed in the Ce, the Me and Ahi. Unilateral lesions located in the Ce and adjacent areas caused an ipsilateral decrease in CRFI fibre number in the lateral hypothalamic area (LH), mesencephalic reticular formation (RF), dorsal (Dpb) and ventral (Vpb) parabrachial nuclei, mesencephalic nucleus of the trigeminal nerve (MeV) and in the lateral division of the bst (bstl). In addition, ipsilateral CRFI fibres decreased in number in the core and shell of the VMH after unilateral lesions of the corticomedial amygdala (CoM) and ventral subiculum (S). These findings suggest that the CRFI cells in the Ce and adjacent areas innervate the Dpb, Vpb and MeV through the LH and RF; the CRFI fibres in the bstl are supplied by the Ce and adjacent areas; and the CoM and S give rise to the CRFI fibres to the VMH. The distribution of retrogradely transported HRP has confirmed these projections. Furthermore, combined HRP and immunohistochemical staining has demonstrated double labeled cells in the Ce following HRP injection into the Dpb, Vpb, MeV and bstl. This provides direct evidence for the amygdalofugal CRF-containing projections to the lower brainstem and bstl. Double-labeled cells were not seen in the CoM and S after HRP injection into the VMH.     

The efferent connections of the ventromedial nucleus of the hypothalamus of the rat.

The efferent connections of the ventromedial nucleus of the hypothalamus (VMH) of the rat have been examined using the autoradiographic method. Following injections of small amounts (0.4-2.0 muCi) of tritium labeled amino acids, fibers from the VMH can be traced forward through the periventricular region, the medial hypothalamus and the medial forebrain bundle to the preoptic and thalamic periventricular nuclei, to the medial and lateral preoptic areas, to the bed nucleus of the stria terminalis and to the ventral part of the lateral septum. Some labeled axons continue through the bed nucleus of the stria terminalis into the stria itself, and hence to the amygdala, where they join other fibers which follow a ventral amygdalopetal route from the lateral hypothalamic area and ventral supraoptic commissure. These fibers terminate in the dorsal part of the medial amygdaloid nucleus and in the capsule of the central nucleus. A lesser number of rostrally directed fibers from the VMH crosses the midline in the ventral supraoptic commissure and contributes a sparse projection to the contralateral amygdala. Descending fibers from the VMH take three routes: (i) through the medial hypothalamus and medial forebrain bundle; (ii) through the periventricular region; and (iii) bilaterally through the ventral supraoptic commissure. These three pathways are interconnected by labeled fibers so that it is not possible to precisely identify their respective terminations. However, the periventricular fibers seem to project primarily to the posterior hypothalamic area and central gray, as far caudally as the anterior pole of the locus coeruleus, while the medial hypothalamic and medial forebrain bundle fibers apparently terminate mainly in the capsule of the mammillary complex, in the supramammillary nucleus and in the ventral tegmental area. The ventral supraoptic commissure fibers leave the hypothalamus closely applied to the medial edges of the two optic tracts. After giving off their contributions to the amygdala, they continue caudally until they cross the dorsal edge of the cerebral peduncle to enter the zona incerta. Some fibers probably terminate here, but others continue caudally to end in the dentral tegmental fields, and particularly in the peripeduncular nucleus. Within the hypothalamus, the VMH appears to project extensively to the surrounding nuclei. However, we have not been able to find evidence for a projection from the VMH to the median eminence. Isotope injections which differentially label the dorsomedial or the ventrolateral parts of the VMH have shown that most of the long connections (to the septum, amygdala, central tegmental fields and locus coeruleus) originate in the ventrolateral VMH, and there is also some evidence for a topographic organization within the projections of this subdivision of the nucleus.