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.     

Some observations on hypothalamo-amygdaloid connections in the monkey

The projections of the hypothalamus to the amygdala have been studied autoradiographically in a series of eleven cynomolgus monkeys (Macaca fascicularis) in which injections of [³H]amino acids had been made in different regions of the caudal two-thirds of the hypothalamus.The most prominent projection arises from the ventromedial nucleus of the hypothalamus and terminates most heavily in the medial, magnocellular division of the central nucleus. Injections confined to the ventromedial nucleus also result in labeling of the piriform cortex, the periamygdaloid cortex, the anterior amygdaloid area, the medial amygdaloid nucleus and the parvocellular divisions of both the basal and basal accessory nuclei. All these projections are bilateral (although the contralateral component is much smaller) and show evidence of a rostro-caudal topographic organization. Isotope injections that involve the caudal part of the lateral hypothalamic area label projections to the medial division of the central amygdaloid nucleus, to the medial and cortical nuclei and to the anterior amygdaloid area. When such caudally placed injections also involved the lateral mamillary nucleus, the lateral division of the central amygdaloid nucleus was additionally labeled. Although the medial mamillary nucleus does not project to the amygdala, there is evidence for a minor projection from the supramamillary region to the medial amygdaloid nucleus. The ventral tegmental area appears to project to the lateral division of the central nucleus and the medial portion of the substantia nigra has a small projection to both divisions of the central nucleus. All of these projections reach the amygdala by way of the so-called ventral amygdalofugal pathway, but at least some of the fibers that arise in the ventromedial nucleus run in the stria terminalis.     

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.     

Projections of the nucleus and tracts of the stria terminalis following lesions at the level of the anterior commissure.

The projections of the stria terminalis were traced with the Fink-Heimer stain following lesions at the level of the anterior commissure. The pre-commissural 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.     

Amygdalo-hypothalamic projections in the lizard Podarcis hispanica: A combined anterograde and retrograde tracing study

The cells of origin and terminal fields of the amygdalo-hypothalamic projections in the lizard Podarcis hispanica were determined by using the anterograde and retrograde transport of the tracers, biotinylated dextran amine and horseradish peroxidase. The resulting labeling indicated that there was a small projection to the preoptic hypothalamus, that arose from the vomeronasal amygdaloid nuclei (nucleus sphericus and nucleus of the accessory olfactory tract), and an important projection to the rest of the hypothalamus, that was formed by three components: medial, lateral, and ventral. The medial projection originated mainly in the dorsal amygdaloid division (posterior dorsal ventricular ridge and lateral amygdala) and also in the centromedial amygdaloid division (medial amygdala and bed nucleus of the stria terminalis). It coursed through the stria terminalis and reached mainly the retrochiasmatic area and the ventromedial hypothalamic nucleus. The lateral projection originated in the cortical amygdaloid division (ventral anterior and ventral posterior amygdala). It coursed via the lateral amygdalofugal tract and terminated in the lateral hypothalamic area and the lateral tuberomammillary area. The ventral projection originated in the centromedial amygdaloid division (in the striato-amygdaloid transition area), coursed through the ventral peduncle of the lateral forebrain bundle, and reached the lateral posterior hypothalamic nucleus, continuing caudally to the hindbrain. Such a pattern of the amygdalo-hypothalamic projections has not been described before, and its functional implications in the transfer of multisensory information to the hypothalamus are discussed. The possible homologies with the amygdalo-hypothalamic projections in mammals and other vertebrates are also considered. J. Comp. Neurol. 384:537–555, 1997. © 1997 Wiley-Liss, Inc.     

Efferent connections of the substantia innominata in the rat

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Amygdaloid and pontine projections to the ventromedial nucleus of the hypothalamus

Amygdaloid and pontine projections to the feline ventromedial nucleus of the hypothalamus (HVM) were studied with retrograde transport of horseradish peroxidase (HRP) and anterograde transport of tritiated amino acids. Following injections of HRP into HVM, amygdaloid neurons were labeled in the ipsilateral cortical and medial nuclei and the ventral portion of the parvocellular part of the basal nucleus. In experiments in which HRP was injected into the tuberal hypothalamus following stria terminalis lesions, it was determined that amygdaloid neurons projecting to HVM by way of the stria terminalis were located in the cortical and medial nuclei while those projecting through another route, presumably the ventral amygdalofugal pathway, were found in the rostral part of the medial nucleus and the parvocellular basal nucleus. Following HRP injection into lateral hypothalamus at the level of HVM, labeled neurons were seen in the magnocellular basal nucleus. After preoptic injections, neurons containing the HRP reaction product were in cortical and medial nuclei and magnocellular and parvocellular parts of the basal nucleus. In addition to cells in the amygdala, rostral pontine neurons were labeled after HRP injections into HVM. The cells were located ipsilateral to the injection, mostly in the dorsal nucleus of the lateral lemniscus, lateral and dorsolateral to the brachium conjunctivum. The pontine cells labeled following HVM injections of HRP were different from those labeled following lateral hypothalamic and preoptic region injections. The pontine projection to HVM was confirmed using axoplasmic transport autoradiography. A mixture of tritiated leucine and tritiated proline was injected into the lateral pontine region labeled after HRP injections into HVM. Labeled axons ascending in the medial forebrain bundle terminated throughout the rostro-caudal extent of HVM.     

Afferent and efferent connections of the olfactory bulbs in the lizard Podarcis hispanica.

The connections of the olfactory bulbs of Podarcis hispanica were studied by tract-tracing of injected horseradish peroxidase. Restricted injections into the main olfactory bulb (MOB) resulted in bilateral terminallike labeling in the medial part of the anterior olfactory nucleus (AON) and in the rostral septum, lateral cortex, nucleus of the lateral olfactory tract, and ventrolateral amygdaloid nucleus. Bilateral retrograde labeling was found in the rostral lateral cortex and in the medial and dorsolateral AON. Ipsilaterally the dorsal cortex, nucleus of the diagonal band, lateral preoptic area, and dorsolateral amygdala showed labeled cell bodies. Retrogradely labeled cells were also found in the midbrain raphe nucleus. Results from injections into the rostral lateral cortex and lateral olfactory tract indicate that the mitral cells are the origin of the centripetal projections of the MOB. Injections in the accessory olfactory bulb (AOB) produced ipsilateral terminallike labeling of the ventral AON, bed nucleus of the accessory olfactory tract, central and ventromedial amygdaloid nuclei, medial part of the bed nucleus of the stria terminalis, and nucleus sphericus. Retrograde labeling of neurons was observed ipsilaterally in the bed nucleus of the accessory olfactory tract and stria terminalis, in the central amygdaloid nucleus, dorsal cortex, and nucleus of the diagonal band. Bilateral labeling of somata was found in the ventral AON, the nucleus sphericus (hilus), and in the mesencephalic raphe nucleus and locus coeruleus. Injections into the dorsal amygdala showed that the mitral neurons are the cells of origin of the AOB centripetal projections. Reciprocal connections are present between AOB and MOB. To our knowledge, this is the first study to address the afferent connections of the olfactory bulbs in a reptile. On the basis of the available data, a discussion is provided of the similarities and differences between the reptilian and mammalian olfactory systems, as well as of the possible functional role of the main olfactory connections in reptiles.     

Efferents from the medial anterior hypothalamic area in the guinea pig

Medial anterior hypothalamic connections were studied with H³-proline and autoradiography. Most of the axons projected to other hypothalamic nuclei. The major pathways were found ventral medial to the fornix and in the periventricular tract. Substantial projections were apparent in the ventromedial and dorsomedial nuclei with less label in the arcuate nucleus. The dorsal premammillary nuclei were labeled bilaterally, particularly with more caudal injections of anterior hypothalamus. Efferents were evident in the posterior hypothalamus and continued into the central gray of the midbrain. Labeled fibers reached the ventral tegmental area and in the reticular formation were traced only through pons. Rostral projections were to the medial and lateral preoptic areas and ventral lateral septum. The bed nucleus of stria terminalis was labeled and a very few fibers reached the medial amygdaloid nucleus. The periventricular nucleus of thalamus was labeled.     

Neural associations of the substantia innominata in the rat: afferent connections

The afferent connections of the substantia innominata (SI) in the rat were determined employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), in combination with histochemical procedures to characterize the neuropil of the SI and identify cholinergic cells. Both neurochemical and connectional data establish that the SI is organized into a dorsal and a ventral division. Each of these divisions is strongly affiliated with a different region of the amygdala, and, together with its amygdalar affiliate, forms part of one of two largely distinct constellations of interconnected forebrain and brainstem cell groups. The dorsal SI receives selective innervation from the lateral part of the bed nucleus of the stria terminalis, the central and basolateral nuclei of the amygdala, the fundus of the striatum, distinctive perifornical and caudolateral zones of the lateral hypothalamus, and caudal brainstem structures including the dorsal raphe nucleus, parabrachial nucleus, and nucleus of the solitary tract. Projections preferentially directed to the ventral SI arise from the medial part of the bed nucleus of the stria terminalis, the rostral two-thirds of the medial nucleus of the amygdala, a large region of the rat amygdala that lies ventral to the central nucleus, the medial preoptic area, anterior hypothalamus, medialmost lateral hypothalamus, and the ventromedial hypothalamus. Both SI divisions appear to receive afferents from the dorsomedial and posterior hypothalamus, supramammillary region, ventral tegmental area, and the peripeduncular area of the midbrain. Projections to the SI whose selectivity was not determined originate from medial prefrontal, insular, perirhinal, and entorhinal cortex and from midline thalamic nuclei. Findings from both PHA-L and WGA-HRP experiments additionally indicate that cell groups preferentially innervating a single SI division maintain numerous projections to one another, thus forming a tightly linked assembly of structures. In the rat, cholinergic neurons that are scattered throughout the SI and in parts of the globus pallidus make up a cell population equivalent to the primate basal nucleus of Meynert (Mesulam et al.: Neuroscience 10:1185-1201, '83). PHA-L-filled axons, labelled from lectin deposits in the dorsal raphe nucleus, peripeduncular area, ventral tegmental area, or caudomedial hypothalamus were occasionally seen to approach individual cholinergic neurons int he SI, and to contact the surface of such cells with axonal varicosities (putative synaptic boutons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Coexistence of somatostatin with neuropeptide Y, but not with cholecystokinin or vasoactive intestinal peptide, in neurons of the rat amygdala

A two-color immunoperoxidase procedure was used to determine whether somatostatin (SOM) containing neurons in the amygdala also contain neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), or cholecystokinin (CCK). There was no evidence that SOM-containing neurons in any of the amygdaloid nuclei contain VIP or CCK. In contrast, there was extensive colocalization of SOM and NPY in all of the amygdaloid nuclei with the exception of the intercalated masses and the lateral subdivision of the central nucleus. The greatest number of SOM-NPY double-labeled cells was observed in the medial nucleus, lateral nucleus, and intra-amygdaloid portion of the bed nucleus of the stria terminalis. The morphology of these SOM-NPY neurons was similar in all nuclei. Most exhibited fusiform or avoid cell bodies with one or two sparsely branched dendrites emerging from each pole of the cell. The extensive coexistence of SOM and NPY in non-pyramidal neurons of the basolateral amygdala is similar to that seen in the cerebral cortex and supports the concept that these brain regions share many important characteristics. The extensive colocalization of SOM and NPY in the medial amygdala, in conjuction with the results of previous studies, suggests that some of these cells may project to the bed nucleus of the stria terminalis and hypothalamus.     

Morphology and axonal projection pattern of neurons in the telencephalon of the fire-bellied toad Bombina orientalis: an anterograde, retrograde, and intracellular biocytin labeling study

The connectivity and cytoarchitecture of telencephalic centers except dorsal and medial pallium were studied in the fire-bellied toad Bombina orientalis by anterograde and retrograde biocytin labeling and intracellular biocytin injection (total of 148 intracellularly labeled neurons or neuron clusters). Our findings suggest the following telencephalic divisions: (1) a central amygdala-bed nucleus of the stria terminalis in the caudal midventral telencephalon, connected to visceral-autonomic centers; (2) a vomeronasal amygdala in the caudolateral ventral telencephalon receiving input from the accessory olfactory bulb and projecting mainly to the preoptic region/hypothalamus; (3) an olfactory amygdala in the caudal pole of the telencephalon lateral to the vomeronasal amygdala receiving input from the main olfactory bulb and projecting to the hypothalamus; (4) a medial amygdala receiving input from the anterior dorsal thalamus and projecting to the medial pallium, septum, and hypothalamus; (5) a ventromedial column formed by a nucleus accumbens and a ventral pallidum projecting to the central amygdala, hypothalamus, and posterior tubercle; (6) a lateral column constituting the dorsal striatum proper rostrally and the dorsal pallidum caudally, and a ventrolateral column constituting the ventral striatum. We conclude that the caudal mediolateral complex consisting of the extended central, vomeronasal, and olfactory amygdala of anurans represents the ancestral condition of the amygdaloid complex. During the evolution of the mammalian telencephalon this complex was shifted medially and involuted. The mammalian basolateral amygdala apparently is an evolutionary new structure, but the medial portion of the amygdalar complex of anurans reveals similarities in input and output with this structure and may serve similar functions.     

The amygdala of the box turtle, Terrapene c. carolina

The amygdala of the box turtle lies beneath the posterior hypopallial ridge. Three nuclear groups may be distinguished in it: (1) the anterior amygdaloid area, (2) the basolateral group and (3) the corticomedial group. The anterior amygdaloid area shows no subdivisions; its location ventral and ventromedial to the caudal part of the small-celled portion of the piriform area is evident. The basolateral group is subdivided into lateral and basal amygdaloid nuclei. The interconnections of this group through the anterior commissure with the comparable area in the opposite amygdala and with the corticomedial group indicate that it is functionally a vicarious cortex. The corticomedial group is divisible into medial and cortical amygdaloid nuclei. The medial nucleus is poorly defined. The cortical nucleus is bounded by the medial amygdaloid nucleus on the medial side and the ventral border of the piriform cortex laterally, and is comparable to the cortical amygdaloid nucleus of higher vertebrates. The lateral olfactory tract arises from mitral cells of the olfactory bulb and accessory olfactory bulb and neurons of the anterior olfactory nucleus. The lateral part of the anterior olfactory nucleus, the lateral and the intermediate parts of the tuberculum olfactorium and the small-celled part of the piriform cortex contribute to and receive fibers from the lateral olfactory tract. The lateral olfactory tract sends fibers to the anterior amygdaloid area and the corticomedial group. The lateral corticohabenular tract has an anterior and a posterior division. The anterior division arises from cells of the nucleus of the lateral olfactory tract and the lateroventral portion of the piriform cortex. It is joined by those fascicles arising in the corticomedial group and designated as the amygdalohabenular tract. This tract crosses in the habenular commissure and retraces its course to enter the corticomedial amygdaloid nuclear group on the side opposite its origin. The basolateral group is interconnected through the anterior commissure. The stria terminalis contains three components which interconnect the corticomedial amygdaloid nuclear group with the septum, the preoptic area and the hypothalamus. The supracommissural and the intracommissural components relate the cortical and the medial nuclei to the septum, the preoptic area and the hypothalamus of the same side. The infracommissural component interconnects the cortical and the medial amygdaloid nuclei with the septum, the preoptic area and the hypothalamus of the same and the opposite side. The dorsal and the ventral olfactory projection tracts arise from the corticomedial amygdaloid nuclear group. They terminate in the preoptic area and anterior hypothalamus.     

Efferent connections of the lateral hypothalamic area of the rat: An autoradiographic investigation

The efferent projections of the lateral hypothalamic area (LHA) at mid-tuberal levels were examined with the autoradiographic tracing method. Connections were observed to widespread regions of the brain, from the telencephalon to the medulla. Ascending fibers course through LHA and the lateral preoptic area and lie lateral to the diagonal band of Broca. Fibers sweep dorsally into the lateral septal nucleus, cingulum bundle and medial cortex. Although sparse projections are found to the ventromedial hypothalamic nucleus, a prominent pathway courses to the dorsal and medial parvocellular subnuclei of the paraventricular nucleus. Labeled fibers in the stria medullaris project to the lateral habenular nucleus. The central nucleus of the amygdala is encapsulated by fibers from the stria terminalis and the ventral amygdalofugal pathway. The substantia innominate, nucleus paraventricularis of the thalamus, and bed nucleus of the stria terminalis also receive LHA fibers. Three descending pathways course to the brainstem: (1) periventricular system, (2) central tegmental tract (CTT), and (3) medial forebrain bundle (MFB). Periventricular fibers travel to the ventral and lateral parts of the midbrain central gray, dorsal raphe nucleus, and laterodorsal tegmental nucleus of the pens. Dorsally coursing fibers of CTT enter the central tegmental field and the lateral and medial parabrachial nuclei. The intermediate and deep layers of the superior colliculus receive some fibers. Fibers from CTT leave the parabranchial region by descending in the ventrolateral pontine and medullary reticular formation; some of these fibers sweep dorsomedially into the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and nucleus commissuralis. From MFB, fibers descend into the ventral tegmental area and to the border of the median raphe and raphe magnus nuclei.     

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.     

Differential projections of habenular nuclei

Lesions were made in the lateral and medial habenular nuclei of the cat. Subsequent degeneration of nerve fibers and terminalis was studied using Nauta-Gygax silver technique. The medial and lateral habenular nuclei project differentially to the septum, olfactory, tubercle, thalamus, midbrain tegmentum and tectum. The diffuse part of the habenulopeduncular tract rises from the lateral habenular nucleus and the compact part rises from both nuclei. Degenerating terminals were seen caudally in the following nuclei: interpeduncular, central superior, dorsal raphae, ventral tegmental (from the medial habenular nucleus), dosral tegmental (from the lateral habenular nucleus), pretectal area, superior colliculus and inferior colliculus (from the lateral habenular nucleus). Rostral projections course in the medial part of the stria medullaris from the medial habenular nucleus and in the lateral part of the stria medullaris from the lateral habenular nucleus: Degenerating terminals were seen rostrally in the following nuclei: dorsomedial, anteroventral, anterodorsal, paraventricular, posterior medial septal (from the medial habenular nucleus) and preoptic area (from the lateral habenular nucleus). Projections occur from the medial habenular nucleus to the amygdala via the stria terminalis. The habenular nuclei are considered to be structures of the limbic system which are differentially related to midbrain, thalamic, amygdaloid, septal and preoptic structures via feedback circuits.     

An HRP study of the afferent connections to rat medial hypothalamic region

Afferent connections to the medial hypothalamic region in the rat were studied using horseradish peroxidase (HRP). HRP was injected iontophoretically by a parapharyngeal approach. After HRP injections into the ventromedial hypothalamic nucleus, labeled cells were found mainly in the medial and basolateral amygdaloid nuclei, subiculum, peripeduncular nucleus and the parabrachial area. Labeled cells following HRP injections into the dorsomedial hypothalamic nucleus were found mainly in the lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, pontine central gray and the parabrachial area. HRP-labeled cells following the medial preoptic area injections were found mainly in the infralimbic cortex, lateral and medial septal nuclei, nucleus accumbens, diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, subiculum, peripedunclar nucleus and the parabrachial area. The intrahypothalamic connections were also discussed.     

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.     

Substance P in the amygdaloid complex, bed nucleus and stria terminalis of the rat brain

Radioimmunoassay and immunohistochemical techniques have demonstrated the presence of substance P in the medial and central nuclie of the amygdala and the bed nucleus of the stria terminalis. Hemisections and micro-knife cuts transecting the anterior, posterior, medial, lateral and ventral connections to the amygdala did not modify the content of substance P in the amygdala. In addition knife cuts totally isolating the medial amygdaloid nucleus from lateral and anterior-posterior connections did not reduce the substance P content of the medial nucleus, but produced a 70% reduction in the substance P content of the central nucleus. These results suggest that substance P containing neurones in the medial and central amygdaloid nuclei do not receive substance P projections originating outside the amygdala. However, there appears to be a short substance P projection from the medial nucleus to the central nucleus.