Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain.

The organization of axonal projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats. Within the BST, the oval nucleus (BSTov) projects very densely to the fusiform nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal area, rhomboid nucleus, and subcommissural zone. Outside the BST, its heaviest inputs are to the caudal substantia innominata and adjacent central amygdalar nucleus, retrorubral area, and lateral parabrachial nucleus. It generates moderate inputs to the caudal nucleus accumbens, parasubthalamic nucleus, and medial and ventrolateral divisions of the periaqueductal gray, and it sends a light input to the anterior parvicellular part of the hypothalamic paraventricular nucleus and nucleus of the solitary tract. The BSTfu displays a much more complex projection pattern. Within the BST, it densely innervates the anterodorsal area, dorsomedial nucleus, and caudal anterolateral area, and it moderately innervates the BSTov, subcommissural zone, and rhomboid nucleus. Outside the BST, the BSTfu provides dense inputs to the nucleus accumbens, caudal substantia innominata and central amygdalar nucleus, thalamic paraventricular nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic dorsomedial nucleus, perifornical lateral hypothalamic area, and lateral tegmental nucleus. Moderately dense inputs are found in the parastrial, tuberal, dorsal raphé, and parabrachial nuclei and in the retrorubral area, ventrolateral division of the periaqueductal gray, and pontine central gray. Light projections end in the olfactory tubercle, lateral septal nucleus, posterior basolateral amygdalar nucleus, supramammillary nucleus, and nucleus of the solitary tract. These and other results suggest that the BSTov and BSTfu are basal telencephalic parts of a circuit that coordinates autonomic, neuroendocrine, and ingestive behavioral responses during stress.     

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.     

Organization of axonal projections from the anterolateral area of the bed nuclei of the stria terminalis

The anterolateral group of the bed nuclei of the stria terminalis (BSTalg) contains four distinct cell groups embedded within an undifferentiated anterolateral area (BSTal) that architectonically resembles a subjacent subcommissural zone (BSTsc). The overall distributions of axonal projections from various regions of the BSTal and from the BSTsc were determined with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracer method and found to be identical. The BSTal and BSTsc share dense bidirectional connections, and also project heavily within the BST to the rhomboid and fusiform nuclei and the anteroventral and anterodorsal areas. They project less densely to the juxtacapsular, oval, magnocellular, ventral, and interfascicular BST nuclei. Outside the BST, brain areas receiving strong to moderate inputs from the BSTal and BSTsc fall into several functional groups: somatomotor system (nucleus accumbens, substantia innominata, ventral tegmental area, and retrorubral area and adjacent midbrain reticular nucleus), central autonomic control system (central amygdalar nucleus, dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, parabrachial nucleus, and nucleus of the solitary tract), neuroendocrine system (paraventricular and supraoptic nuclei, hypothalamic visceromotor pattern generator network), and thalamocortical feedback loops (midline, medial, and intralaminar nuclei). The results indicate that the BSTal and BSTsc are parts of the same cell group (dorsal and ventral to the anterior commissure), which plays a role in coordinating visceral and somatic motor responses (during ingestive behaviors, for example), especially in response to noxious stimuli (learned anorexia associated with noxious stimuli). BSTal projections are distinct from those of the adjacent juxtacapsular, oval, fusiform, and rhomboid nuclei.     

Projections from bed nuclei of the stria terminalis, anteromedial area: cerebral hemisphere integration of neuroendocrine, autonomic, and behavioral aspects of energy balance

The anteromedial area of the bed nuclei of the stria terminalis (BSTam) is the relatively undifferentiated region of the anterior medial (anteromedial) group of the bed nuclei of the stria terminalis (BSTamg), which also includes the more distinct dorsomedial, magnocellular, and ventral nuclei. The overall pattern of axonal projections from the rat BSTam was analyzed with the Phaseolus vulgaris-leucoagglutinin anterograde pathway tracing method. Brain areas receiving relatively moderate to strong inputs from the BSTam fall into five general categories: neuroendocrine system (regions containing pools of magnocellular oxytocin neurons, and parvicellular corticotropin-releasing hormone, thyrotropin-releasing hormone, somatostatin, and dopamine neurons); central autonomic control network (central amygdalar nucleus, descending paraventricular nucleus, and ventrolateral periaqueductal gray); hypothalamic visceromotor pattern generator network (five of six known components); behavior control column (descending paraventricular nucleus and associated arcuate nucleus; ventral tegmental area and associated nucleus accumbens and substantia innominata); and behavioral state control (supramammillary and tuberomammillary nuclei). The BSTam projects lightly to thalamocortical feedback loops (via the medial-midline-intralaminar thalamus). Its pattern of axonal projections, combined with its pattern of neural inputs (the most varied of all BST cell groups), suggests that the BSTam is part of a striatopallidal differentiation involved in coordinating neuroendocrine, autonomic, and behavioral or somatic responses associated with maintaining energy balance homeostasis.     

Axonal projections from the parasubthalamic nucleus

The parasubthalamic nucleus (PSTN) is a differentiation of the lateral hypothalamic area, characterized by a distinct population of neurons expressing beta-preprotachykinin (beta-PPT) mRNA. The axonal projections from the PSTN have been analyzed with the PHAL anterograde tract tracing method in rats. The results indicate that the cell group is distinguished by massive projections to parasympathetic preganglionic neurons in the brainstem (especially in the salivatory nuclei and dorsal motor nucleus of the vagus nerve) and to parts of the parabrachial nucleus and nucleus of the solitary tract that relay viscerosensory and gustatory information. In addition, the PSTN projects to cortical parts of the cerebral hemisphere (infralimbic, agranular insular, postpiriform transition and lateral entorhinal areas, and posterior basolateral amygdalar nucleus)-directly and also indirectly via thalamic feedback loops involving the paraventricular and mediodorsal nuclei-and to nuclear parts of the cerebral hemisphere (central amygdalar nucleus, striatal fundus, rhomboid nucleus of the bed nuclei of the stria terminalis, and substantia innominata). The PSTN is thus positioned to influence directly many cerebral hemisphere and hindbrain components of the central parasympathetic control network that is active, for example, during feeding behavior and cardiovascular regulation.     

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.     

Cortical,thalamic, and amygdaloid connections of the anterior and posterior insular cortices

Cortical, thalamic, and amygdaloid projections of the rat anterior and posterior insular cortices were examined using the anterograde transport of biocytin. Granular and dysgranular posterior insular areas between bregma and 2 mm anterior to bregma projected to the gustatory thalamic nucleus. Granular cortex projected to the subjacent dysgranular cortex which in turn projected to the agranular (all layers) and granular cortices (layers I and VI). Both granular and dysgranular posterior areas projected heavily to the dysgranular anterior insular cortex. Agranular posterior insular cortex projected to medial mediodorsal nucleus, agranular anterior insular and infralimbic cortices as well as granular and dysgranular posterior insula. No projections to the amygdala were observed from posterior granular cortex, although dysgranular cortex projected to the lateral central nucleus, dorsolateral lateral nucleus, and posterior basolateral nucleus. Agranular projections were similar, although they included medial and lateral central nucleus and the ventral lateral nucleus. Dysgranular anterior insular cortex projected to lateral agranular frontal cortex and granular and dysgranular posterior insular regions. Agranular anterior insular cortex projected to the dysgranular anterior and prelimbic cortices. Anterior insuloamygdaloid projections targeted the rostral lateral and anterior basolateral nuclei with sparse projections to the rostral central nucleus. The data suggest that the anterior insula is an interface between the posterior insular cortex and motor cortex and is connected with motor-related amygdala regions. Amygdaloid projections from the posterior insular cortex appear to be organized in a feedforward parallel fashion targeting all levels of the intraamygdaloid connections linking the lateral, basolateral, and central nuclei . J. Comp. Neurol. 399:440–468, 1998. © 1998 Wiley-Liss, Inc.     

Projections from bed nuclei of the stria terminalis, posterior division: implications for cerebral hemisphere regulation of defensive and reproductive behaviors

The posterior division of the bed nuclei of the stria terminalis has three major nuclei: principal, interfascicular, and transverse, which receive topographically ordered inputs from the medial amygdalar nucleus. The overall pattern of axonal projections from each nucleus was determined in male rats with the Phaseolus vulgaris-leucoagglutinin method. Together, these nuclei project topographically back to the medial amygdalar nucleus, to the adjacent lateral septal nucleus, to the nucleus accumbens and substantia innominata, to hypothalamic parts of the behavior control column, and to the hypothalamic periventricular region, which controls patterned neuroendocrine and autonomic responses. The principal nucleus preferentially innervates septal and hypothalamic regions that control reproductive behavior and visceromotor responses, confirming a similar analysis by Gu et al. (J Comp Neurol [2003] 460:542-562). In contrast, the interfascicular and transverse nuclei differentially innervate septal and hypothalamic regions that control defensive as well as reproductive behaviors. In addition, the transverse nucleus projects significantly to midbrain parts of the behavior control column concerned with foraging/exploratory behavior. All three posterior division nuclei also project to thalamocortical feedback loops (by means of the nucleus reuniens and paraventricular nucleus). These structural data may be interpreted to suggest that the bed nuclei posterior division forms part (pallidal) of a corticostriatopallidal system involved in controlling two major classes of social (defensive and reproductive) behavior.     

Topography of projections from the medial prefrontal cortex to the amygdala in the rat

The projections from the rat medial prefrontal cortex to the amygdaloid complex were investigated using retrograde transport of fluorescent dyes and anterograde transport of horseradish peroxidase-WGA. The ventral anterior cingulate, prelimbic, infralimbic and medial orbital areas and the taenia tecta were found to project to the amygdaloid complex. The projections from the prelimbic area arose bilaterally. The medial orbital, prelimbic and anterior cingulate areas send convergent projections to the basolateral nucleus. The prelimbic area has additional projections to the posterolateral cortical nucleus and amygdalo-hippocampal area. The infralimbic area does not project to the basolateral nucleus and cortico-amygdaloid projections from this area are focussed on the anterior cortical nucleus and the anterior amygdaloid area. Both prelimbic and infralimbic areas project to an area situated between the central, medial and basomedial nuclei. Based on similar projections, this area appears to be a caudal continuation of the anterior amygdaloid area. The results indicate that the medial prefrontal component of the "basolateral limbic circuit" is restricted to the anterior cingulate and prelimbic areas. No evidence was obtained to support the existence of a medial prefronto-amygdaloid component of the "visceral forebrain".     

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.     

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 from bed nuclei of the stria terminalis, dorsomedial nucleus: implications for cerebral hemisphere integration of neuroendocrine, autonomic, and drinking responses

The overall projection pattern of a tiny bed nuclei of the stria terminalis anteromedial group differentiation, the dorsomedial nucleus (BSTdm), was analyzed with the Phaseolus vulgaris-leucoagglutinin anterograde pathway tracing method in rats. Many brain regions receive a relatively moderate to strong input from the BSTdm. They fall into eight general categories: humeral sensory-related (subfornical organ and median preoptic nucleus, involved in initiating drinking behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin, vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin, thyrotropin-releasing hormone, corticotropin-releasing hormone), central autonomic control network (central amygdalar nucleus, BST anterolateral group, descending paraventricular hypothalamic nucleus, retrochiasmatic area, ventrolateral periaqueductal gray, Barrington's nucleus), hypothalamic visceromotor pattern-generator network (five of six known components), behavior control column (ingestive: descending paraventricular nucleus; reproductive: lateral medial preoptic nucleus; defensive: anterior hypothalamic nucleus; foraging: ventral tegmental area, along with interconnected nucleus accumbens and substantia innominata), orofacial motor control (retrorubral area), thalamocortical feedback loops (paraventricular, central medial, intermediodorsal, and medial mediodorsal nuclei; nucleus reuniens), and behavioral state control (subparaventricular zone, ventrolateral preoptic nucleus, tuberomammillary nucleus, supramammillary nucleus, lateral habenula, and raphé nuclei). This pattern of axonal projections, and what little is known of its inputs suggest that the BSTdm is part of a striatopallidal differentiation involved in coordinating the homeostatic and behavioral responses associated thirst and salt appetite, although clearly it may relate them to other functions as well. The BSTdm generates the densest known inputs directly to the neuroendocrine system from any part of the cerebral hemispheres.     

A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat.

Ascending projections from the dorsal raphe nucleus (DR) were examined in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from the DR ascended through the forebrain within the medial forebrain bundle. DR fibers were found to terminate heavily in several subcortical as well as cortical sites. The following subcortical nuclei receive dense projections from the DR: ventral regions of the midbrain central gray including the 'supraoculomotor central gray' region, the ventral tegmental area, the substantia nigra-pars compacta, midline and intralaminar nuclei of the thalamus including the posterior paraventricular, the parafascicular, reuniens, rhomboid, intermediodorsal/mediodorsal, and central medial thalamic nuclei, the central, lateral and basolateral nuclei of the amygdala, posteromedial regions of the striatum, the bed nucleus of the stria terminalis, the lateral septal nucleus, the lateral preoptic area, the substantia innominata, the magnocellular preoptic nucleus, the endopiriform nucleus, and the ventral pallidum. The following subcortical nuclei receive moderately dense projections from the DR: the median raphe nucleus, the midbrain reticular formation, the cuneiform/pedunculopontine tegmental area, the retrorubral nucleus, the supramammillary nucleus, the lateral hypothalamus, the paracentral and central lateral intralaminar nuclei of the thalamus, the globus pallidus, the medial preoptic area, the vertical and horizontal limbs of the diagonal band nuclei, the claustrum, the nucleus accumbens, and the olfactory tubercle. The piriform, insular and frontal cortices receive dense projections from the DR; the occipital, entorhinal, perirhinal, frontal orbital, anterior cingulate, and infralimbic cortices, as well as the hippocampal formation, receive moderately dense projections from the DR. Some notable differences were observed in projections from the caudal DR and the rostral DR. For example, the hippocampal formation receives moderately dense projections from the caudal DR and essentially none from the rostral DR. On the other hand, virtually all neocortical regions receive significantly denser projections from the rostral than from the caudal DR. The present results demonstrate that dorsal raphe fibers project significantly throughout widespread regions of the midbrain and forebrain.     

Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio)

Connections of the medial precommissural subpallial ventral telencephalon, i.e., dorsal (Vd, interpreted as part of striatum) and ventral (Vv, interpreted as part of septum) nuclei of area ventralis telencephali, were studied in the zebrafish (Danio rerio) using two tracer substances (DiI or biocytin). The following major afferent nuclei to Vd/Vv were identified: medial and posterior pallial zones of dorsal telencephalic area, and the subpallial supracommissural and postcommissural nuclei of the ventral telencephalic area, the olfactory bulb, dorsal entopeduncular, anterior and posterior parvocellular preoptic and suprachiasmatic nuclei, anterior, dorsal and central posterior dorsal thalamic, as well as rostrolateral nuclei, periventricular nucleus of the posterior tuberculum, posterior tuberal nucleus, various tuberal hypothalamic nuclei, dorsal tegmental nucleus, superior reticular nucleus, locus coeruleus, and superior raphe nucleus. Efferent projections of the ventral telencephalon terminate in the supracommissural nucleus of area ventralis telencephali, the posterior zone of area dorsalis telencephali, habenula, periventricular pretectum, paracommissural nucleus, posterior dorsal thalamus, preoptic region, midline posterior tuberculum (especially the area dorsal to the posterior tuberal nucleus), tuberal (midline) hypothalamus and interpeduncular nucleus. Strong reciprocal interconnections likely exist between septum and preoptic region/midline hypothalamus and between striatum and dorsal thalamus (dopaminergic) posterior tuberculum. Regarding ascending activating/modulatory systems, the pallium shares with the subpallium inputs from the (noradrenergic) locus coeruleus, and the (serotoninergic) superior raphe, while the subpallium additionally receives such inputs from the (dopaminergic) posterior tuberculum, the (putative cholinergic) superior reticular nucleus, and the (putative histaminergic) caudal hypothamalic zone.     

Organization of cortical and subcortical projections to area 6m of the cat

By analyzing regional variations of afferent connectivity, we have identified a medial subdivision of feline area 6 (area 6m) which differs from all surrounding sectors of the frontal lobe in its pattern of inputs. Area 6m is located in the ventral bank of the cruciate sulcus and on the adjacent medial face of the frontal lobe and is partially coextensive with the medial frontal eye field as identified previously in electrophysiological experiments. Area 6m is innervated by axons from visual, association, and oculomotor areas and does not receive projections from somesthetic or somatomotor areas. Cortical sources of input to area 6m include several retinotopically organized extrastriate visual areas (AMLS, ALLS, and PLLS), association areas with strong links to the visual system (area 7, granular insula, posterior ectosylvian gyrus, and cingulate gyrus), and a lateral division of area 6 (area 61) with oculomotor functions. Thalamic afferents of area 6m derive from the paralamellar ventral anterior nucleus, from a dorsolateral division of the mediodorsal nucleus, and from the rostral intralaminar nuclei. The claustrum and the basolateral nucleus of the amygdala project to area 6m. Projections from area 7, the posterior cingulate area, the ventral anterior nucleus, and the mediodorsal nucleus are spatially ordered in a pattern such that parts of area 6 close to the fundus of the cruciate sulcus receive input from neurons positioned anteriorly in the cortical areas, dorsolaterally in the ventral anterior nucleus, and ventrolaterally in the mediodorsal nucleus. Our results indicate that area 6m probably is involved in the voluntary control of gaze and attention rather than in skeletomotor functions.     

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)     

Identification of the reptilian basolateral amygdala: an anatomical investigation of the afferents to the posterior dorsal ventricular ridge of the lizard Podarcis hispanica

The presence of multimodal association in the telencephalon of reptiles has been investigated by tracing the afferent connections to the posterior dorsal ventricular ridge (PDVR) of the lizard Podarcis hispanica. The PDVR receives telencephalic afferents from the lateral (olfactory) and dorsal cortices, and from the three unimodal areas of the anterior dorsal ventricular ridge, in a convergent manner. From the diencephalon, it receives afferents from the dorsomedial anterior and medial posterior thalamic nuclei, and from several hypothalamic nuclei. Brainstem afferents to the PDVR originate in the dorsal interpeduncular nucleus, the nucleus of the lateral lemniscus and parabrachial nucleus. The afferents to the thalamic nuclei that project to the PDVR have also been studied. The dorsomedial anterior thalamic nucleus receives projections mainly from limbic structures, whereas the medial posterior thalamic nucleus is the target of projections from structures with a clear sensory significance (optic tectum, torus semicircularis, nuclei of the lateral and spinal lemniscus, superior olive and trigeminal complex). As a result, the PDVR appears as an associative centre that receives visual, auditory, somatosensory and olfactory information from several telencephalic and non-telencephalic centres, and a multimodal projection from the medial posterior thalamic nucleus. This pattern of afferents of the PDVR is similar to that of the caudal neostriatum in birds and the basolateral division of the mammalian amygdala. These results indicate that a multimodal amygdala is already present in reptiles, and has probably played a key role in the evolution of the vertebrate brain.     

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.     

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.     

The origin of projections from the posterior cingulate and retrosplenial cortices to the anterior,medial dorsal and laterodorsal thalamic nuclei of macaque monkeys

Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition.