Efferent connections of the hippocampal formation in the rat.

In this investigation the projections of the hippocampal formation to the septal area and hypothalamus were studied in the rat with the combined use of 3H-amino acid radioautography and horseradish peroxidase histochemistry. The results indicate that all of the fibers which project to the hypothalamus and the majority of fibers which project to the septum arise from the subicular cortex and not from hippocampal pyramidal cells. The projection to both of these areas are topographically organized along the longitudinal axis of the hippocampal formation. Specifically, fibers from subicular cortical cells situated at the septal end of the hippocampal formation which project through the medial part of the dorsal fornix terminate in the dorsomedial quadrant of the lateral septal nucleus and in the dorsal portion of the pars posterior of the medial mammillary nucleus. Fibers from progressively more posteroventral levels of the hippocampal formation which project through more lateral portions of the dorsal fornix and fimbria terminate in progressively lateral and ventral quadrants of the lateral septal nucleus and in progressively more ventral portions of the pars posterior. Concerning the specific origin of the fornix system, fibers from only the prosubiculum and subiculum project through both the pre- and postcommissural fornix. Hippocampal pyramidal cells from all CA fields have a restricted projection through the precommissural fornix and terminate in the caudal half of the septum while the presubiculum projects solely through the postcommissural fornix. The medial corticohypothalamic tract (MCHT) was found to arise from cells located in anterior ventral levels of the subicular cortex. Fibers from this tract appeared to be distributed throughout the pericellular region of the entire ventromedial extent of the hypothalamus from the level of the suprachiasmatic nucleus through the level of the medial mammillary nucleus. In this way, the mammillary bodies receive input from the subicular cortex via two routes: the descending column of the fornix and the MCHT.     

A [C]2-Deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. III. The hippocampal formation

The regions metabolically activated in the rat brain following focal electrical stimulation of various components of the hippocampal formation were identified with the use of [¹⁴C]2-deoxyglucose (2-DG) autoradiography. The results of these experiments, conducted in the rat, showed that in the absence of elicited afterdischarge activity, stimulation of either the CA1 or CA3 field of the dorsal hippocampus resulted in bilateral metabolic activation of only the dorsal hippocampus as well as of a relatively restricted region within the dorsomedial aspect of the lateral septal nucleus, bilaterally. In contrast, stimulation of either the CA1 or CA3 field of the ventral hippocampus resulted in bilateral activation of the ventral hippocampus and no region of the dorsal hippocampus. Following such stimulation, the lateral septal nucleus was also labeled bilaterally, but the activated regions were situated in a position ventrolateral to those resulting from stimulation at dorsal levels. Stimulation of the subicular cortex, in contrast, resulted in only ipsilateral activation of the hippocampal formation and lateral septal nucleus. Further rostral levels of the lateral septal nucleus were noted to be activated following stimulation of subicular cortex as compared to stimulation of the cornu Ammonis.The hypothalamus was directly activated by two pathways, the postcommissural fornix and the medial corticohypothalamic tract. Following stimulation at dorsal and posterior levels of CA1 and the subiculum, the mammillary bodies were demonstrably labeled by input from the postcommissural fornix. Regions of the medial hypothalamus were activated via the medial corticohypothalamic tract following stimulation of the ventral subiculum.The amygdala, stria terminalis and its bed nucleus were also shown to be demonstrably activated following stimulation of the ventral subiculum, ventral CAl field and posterior prosubiculum. This pathway may represent an additional route by which hippocampal modulation may indirectly modulate hypothalamic function.The presence of elicited afterdischarges resulted in more extensive patterns of metabolic labeling within the hippocampal formation and lateral septal nuclei as compared to experiments in which afterdischarges were not elicited. The extent of the demonstrable labeling, both within, and extrinsic to the hippocampal formation appeared to be a function of the duration and severity of the elicited seizure discharge. Additional structures which were demonstrably labeled following the elicitation of seizure activity include the entorhinal cortex-prepyriform area, amygdala, substantia innominata, putamen, substantia nigra, olfactory and prefrontal cortices and medial thalamic nuclei.     

Connections of the posterior nucleus of the amygdala.

The connections of a relatively homogeneous band of neurons in the caudal amygdala have been examined with anterograde and retrograde axonal tracing methods in the rat. This region, called here the posterior nucleus of the amygdala (PA), corresponds in part to an area that has been referred to as the cortico-amygdaloid transition area, posterior part of the medial nucleus of the amygdala, amygdalo-hippocampal transition area, and posteromedial basal nucleus. Experiments with fluorogold and phaseolus vulgaris leucoagglutinin (PHAL) indicate that the major neuronal input to the PA arises in the ventral premammillary nucleus, and that substantial projections also arise in olfactory-related areas such as the medial nucleus of the amygdala, bed nucleus of the accessory olfactory tract, and posterior cortical nucleus of the amygdala, as well as in the ventral subiculum and adjacent parts of hippocampal field CA1. Other seemingly minor inputs, including cholinergic fibers from the substantia innominata, dopaminergic fibers from the ventral tegmental area, and serotoninergic fibers from the dorsal nucleus of the raphe, were also identified. The efferent projections of the PA as determined with the PHAL method appear to follow five major routes: 1) a relatively small group of laterally directed fibers innervates the dorsal endopiriform nucleus, and a few of these fibers reach cortical area TR and the lateral entorhinal area; 2) another small group of fibers courses medially to innervate the ventral subiculum and adjacent parts of field CA1; 3) many fibers course ventrally to innervate the outer molecular layer of the medial part of the posterior cortical nucleus of the amygdala; 4) a moderate group of fibers courses rostrally to innervate primarily the posterodorsal part of the medial nucleus of the amygdala, although some fibers continue on to end less densely in rostral parts of the medial nucleus of the amygdala before leaving the amygdala through the ansa peduncularis; and 5) the major output of the PA courses through the stria terminalis. One branch of this pathway massively innervates the principal nucleus of the bed nuclei of the stria terminalis before entering the medial hypothalamus, where it ends massively in the anteroventral periventricular and medial preoptic nuclei, ventrolateral part of the ventromedial nucleus and adjacent parts of the basal lateral hypothalamic area, and ventral premammillary nucleus. The other branch sends fibers to the ventral lateral septal nucleus, nucleus accumbens, olfactory tubercle, and infralimbic area of the prefrontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferent projections of the intergeniculate leaflet and the ventral lateral geniculate nucleus in the rat

The intergeniculate leaflet (IGL) and the ventral lateral geniculate nucleus (VLG) are ventral thalamic derivatives within the lateral geniculate complex. In this study, IGL and VLG efferent projections were compared by using anterograde transport of Phaseolus vulgaris-leucoagglutinin and retrograde transport of FluoroGold. Projections from the IGL and VLG leave the geniculate in four pathways. A dorsal pathway innervates the thalamic lateral dorsal nucleus (VLG), the reuniens and rhomboid nuclei (VLG and IGL), and the paraventricular nucleus (IGL). A ventral pathway runs through the geniculohypothalamic tract to the suprachiasmatic nucleus and the anterior hypothalamus (IGL). A medial pathway innervates the zona incerta and dorsal hypothalamus (VLG and IGL); the lateral hypothalamus and perifornical area (VLG); and the retrochiasmatic area (RCA), dorsomedial hypothalamic nucleus, and subparaventricular zone (IGL). A caudal pathway projects medially to the posterior hypothalamic area and periaqueductal gray and caudally along the brachium of the superior colliculus to the medial pretectal area and the nucleus of the optic tract (IGL and VLG). Caudal IGL axons also terminate in the olivary pretectal nucleus, the superficial gray of the superior colliculus, and the lateral and dorsal terminal nuclei of the accessory optic system. Caudal VLG projections innervate the lateral posterior nucleus, the anterior pretectal nucleus, the intermediate and deep gray of the superior colliculus, the dorsal terminal nucleus, the midbrain lateral tegmental field, the interpeduncular nucleus, the ventral pontine reticular formation, the medial and lateral pontine gray, the parabrachial region, and the accessory inferior olive. This pattern of IGL and VLG projections is consistent with our understanding of the distinct functions of each of these ventral thalamic derivatives.     

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.     

An HRP study of the connections of the subfornical organ of the rat

The connections of the subfornical organ (SFO) wer investigated by using the HRP technique. Injections into the SFO labeled neurons in the medial septum, but not in lateral septum nor in the diagonal band nucleus. Labeled cells were observed in the median preoptic nucleus, below the ependyma of the third ventricle, in the dorsal preoptic region near the anterior commissure, and diffusely throughout the medial preoptic and anterior bypothalamic areas. Fibers were followed from the ventral stalk of the SFO. Precommissural fibers enter the median preoptic nucleus where many of them appear to terminate. Others continue on to the medial septum, the OVLT, the supraoptic nucleus, and the suprachiasmatic nucleus, HRP injections into the median preoptic nucleus labled many neurons in the SFO. Postcommissural fibers reach the hypothalamus by descending along the walls of the ventricle in the subependymal space, by traveling in the columns of the fornix and the medial corticohypothalamic tract, or by passing through the paraventricular nucleus of the thalamus. Some postcommissural fibers turn rostrally and enter the median preoptic nucleus while others join precommissural fibers bound for the supraoptic nucleus. More caudally directed fibers appear to innervate the paraventricular nucleus of the hypothalamus and the medial preoptic and anterior hypothalamic areas. HRP injections into the paraventricular nucleus of the hypothalamus labeled neurons in the SFO. These finding corroborate and extend previous work in describing neural connections between two brain regions that are important for fluid blance.     

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 paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat

The paraventricular (PV) and paratenial (PT) nuclei are prominent cell groups of the midline thalamus. To our knowledge, only a single early report has examined PV projections and no previous study has comprehensively analyzed PT projections. By using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, and the retrograde tracer, FluoroGold, we examined the efferent projections of PV and PT. We showed that the output of PV is virtually directed to a discrete set of limbic forebrain structures, including 'limbic' regions of the cortex. These include the infralimbic, prelimbic, dorsal agranular insular, and entorhinal cortices, the ventral subiculum of the hippocampus, dorsal tenia tecta, claustrum, lateral septum, dorsal striatum, nucleus accumbens (core and shell), olfactory tubercle, bed nucleus of stria terminalis (BST), medial, central, cortical, and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and dorsomedial nuclei of the hypothalamus. The posterior PV distributes more heavily than the anterior PV to the dorsal striatum and to the central and basal nuclei of amygdala. PT projections significantly overlap with those of PV, with some important differences. PT distributes less heavily than PV to BST and to the amygdala, but much more densely to the medial prefrontal and entorhinal cortices and to the ventral subiculum of hippocampus. As described herein, PV/PT receive a vast array of afferents from the brainstem, hypothalamus, and limbic forebrain, related to arousal and attentive states of the animal, and would appear to channel that information to structures of the limbic forebrain in the selection of appropriate responses to changing environmental conditions. Depending on the specific complement of emotionally associated information reaching PV/PT at any one time, PV/PT would appear positioned, by actions on the limbic forebrain, to direct behavior toward a particular outcome over a range of outcomes.     

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.     

Efferents from medial basal forebrain and hypothalamus in the rat. II. An autoradiographic study of the anterior hypothalamus.

Using tritiated amino acid autoradiography, the efferent projections of the anterior hypothalamic area (AHA) were studied in albino rats. Axons from AHA neurons were not confined to local projections in the hypothalamus. Ascending AHA axons ran through the preoptic region, joined the diagonal band and distributed in the lateral septum. Descending AHA efferents within the hypothalamus coursed in a bundle ventromedial to the fornix. Projections were observed to the dorsomedial, ventromedial, arcuate and dorsal premammillary nuclei, and to the median eminence. Sweeping dorsomedially in the posterior hypothalamus, some AHA axons distributed in the central grey. AHA axons staying ventral projected to the supramammillary region, ventral tegmental area, raphe nuclei and midbrain reticular formation. Other AHA efferents distributed to the periventricular thalamus, to the medial amygdala via the stria terminalis or supraoptic commissure, and to the lateral habenula through the stria medullaris. For comparison with the AHA, efferent projections from the paraventricular nucleus (PVN) and from the ventromedial nucleus and adjacent basal hypothalamus (VMR) were studied. Projections from PVN neurons were not restricted to the median eminence and neurohypophysis. PVN efferents also distributed to many of the same regions as did those of the AHA but had somewhat different fiber trajectories and longer descending projections. VMR efferents were more widespread than those of the AHA, with projections extending into the lateral zona incerta and pontine reticular formation. Projections from the AHA were distinct from those of the medial preoptic area (mPOA). For example, while AHA axons descended in a bundle ventromedial to the fornix, mPOA axons ran in the medial forebrain bundle. Such anatomical differences may underlie experimentally demonstrated functional differences between the mPOA and AHA, for instance, in mediation of male and female sex behaviors.     

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.     

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 projections to nucleus reuniens of the thalamus

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and the major source of thalamic afferents to the hippocampus and parahippocampal structures. Nucleus reuniens has recently been shown to exert powerful excitatory actions on CA1 of the hippocampus. Few reports on any species have examined afferent projections to nucleus reuniens. By using the retrograde anatomical tracer Fluorogold, we examined patterns of afferent projections to RE in the rat. We showed that RE receives a diverse and widely distributed set of afferents projections. The main sources of input to nucleus reuniens were from the orbitomedial, insular, ectorhinal, perirhinal, and retrosplenial cortices; CA1/subiculum of hippocampus; claustrum, tania tecta, lateral septum, substantia innominata, and medial and lateral preoptic nuclei of the basal forebrain; medial nucleus of amygdala; paraventricular and lateral geniculate nuclei of the thalamus; zona incerta; anterior, ventromedial, lateral, posterior, supramammillary, and dorsal premammillary nuclei of the hypothalamus; and ventral tegmental area, periaqueductal gray, medial and posterior pretectal nuclei, superior colliculus, precommissural/commissural nuclei, nucleus of the posterior commissure, parabrachial nucleus, laterodorsal and pedunculopontine tegmental nuclei, nucleus incertus, and dorsal and median raphe nuclei of the brainstem. The present findings of widespread projections to RE, mainly from limbic/limbic-associated structures, suggest that nucleus reuniens represents a critical relay in the transfer of limbic information (emotional/cognitive) from RE to its major targets, namely, to the hippocampus and orbitomedial prefrontal cortex. RE appears to be a major link in the two-way exchange of information between the hippocampus and the medial prefrontal cortex.     

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)     

An autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat.

The efferent connections of the hippocampal formation of the rat have been re-examined autoradiographically following the injection of small quantities of 3H-amino acids (usually 3H-proline) into different parts of Ammon's horn and the adjoining structures. The findings indicate quite clearly that each component of the hippocampal formation has a distinctive pattern of efferent connections and that each component of the fornix system arises from a specific subdivision of the hippocampus or the adjoining cortical fields. Thus, the precommissural fornix has been found to originate solely in fields CA1-3 of the hippocampus proper and from the subiculum; the projection to the anterior nuclear complex of the thalamus arises more posteriorly in the pre- and/or parasubiculum and the postsubicular area; the projection to the mammillary complex which comprises a major part of the descending columns of the fornix has its origin in the dorsal subiculum and the pre- and/or parasubiculum; and finally, the medial cortico-hypothalamic tract arises from the ventral subiculum. The lateral septal nuclei (and the adjoining parts of the posterior septal complex) constitute the only subcortical projection field of the pyramidal cells in fields CA1-3 of Ammon's horn. There is a rostral extension of the pre-commissural fornix to the bed nucleus of the stria terminalis, the nucleus accumbens, the medial and posterior parts of the anterior olfactory nucleus, the taenia tecta, and the infralimbic area, which appears to arise from the temporal part of field CA1 or the adjacent part of the ventral subiculum. The projection of Ammon's horn upon the lateral septal complex shows a high degree of topographic organization (such that different parts of fields CA1 and CA3 project in an ordered manner to different zones within the lateral septal nucleus). The septal projection of "CA2" and field CA3 is bilateral, while that of field CA1 is strictly unilateral. In addition to its subcortical projections, the hippocampus has been found to give rise to a surprisingly extensive series of intracortical association connections. For example, all parts of fields CA1, CA2 and CA3 project to the subiculum, and at least some parts of these fields send fibers to the pre- and parasubiculum, and to the entorhinal perirhinal, retrosplenial and cingulate areas. From the region of the pre- and parasubiculum there is a projection to the entorhinal cortex and the parasubiculum of both sides. That part of the postsubiculum (= dorsal part of the presubiculum) which we have examined has been found to project to the cingulate and retrosplenial areas ipsilaterally, and to the entorhinal cortex and parasubiculum bilaterally.     

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.     

Cytoarchitecture and efferent projections of the nucleus incertus of the rat

The nucleus incertus is located caudal to the dorsal raphe and medial to the dorsal tegmentum. It is composed of a pars compacta and a pars dissipata and contains acetylcholinesterase, glutamic acid decarboxylase, and cholecystokinin-positive somata. In the present study, anterograde tracer injections in the nucleus incertus resulted in terminal-like labeling in the perirhinal cortex and the dorsal endopyriform nucleus, the hippocampus, the medial septum diagonal band complex, lateral and triangular septum medial amygdala, the intralaminar thalamic nuclei, and the lateral habenula. The hypothalamus contained dense plexuses of fibers in the medial forebrain bundle that spread in nearly all nuclei. Labeling in the suprachiasmatic nucleus filled specifically the ventral half. In the midbrain, labeled fibers were observed in the interpeduncular nuclei, ventral tegmental area, periaqueductal gray, superior colliculus, pericentral inferior colliculus, pretectal area, the raphe nuclei, and the nucleus reticularis pontis oralis. Retrograde tracer injections were made in areas reached by anterogradely labeled fibers including the medial prefrontal cortex, hippocampus, amygdala, habenula, nucleus reuniens, superior colliculus, periaqueductal gray, and interpeduncular nuclei. All these injections gave rise to retrograde labeling in the nucleus incertus but not in the dorsal tegmental nucleus. These data led us to conclude that there is a system of ascending projections arising from the nucleus incertus to the median raphe, mammillary complex, hypothalamus, lateral habenula, nucleus reuniens, amygdala, entorhinal cortex, medial septum, and hippocampus. Many of the targets of the nucleus incertus were involved in arousal mechanisms including the synchronization and desynchronization of the theta rhythm.     

Vasopressin and oxytocin systems in the brain and upper spinal cord of Macaca fascicularis

This paper describes the vasopressin (VP) and oxytocin (OXT) immunoreactive structures in the brain and upper spinal cord of the adult male and female Macaca fascicularis. Immunocytochemistry following intraventricular application of colchicine displayed VP neurons in the diagonal band of Broca (DBB), bed nucleus of the stria terminalis (BST), medial amygdaloid nucleus, dorsomedial hypothalamic nucleus, area of the locus coeruleus (LC), solitary tract nuclei (NTS), and the dorsal horn of the cervical spinal cord in addition to those known to exist in the paraventricular, supraoptic, and suprachiasmatic hypothalamic nuclei. Furthermore, a dense accumulation of VP fibers was observed in areas such as the DBB, medial septum, BST, amygdala, hippocampus, ventral tegmental area, periaquaductal gray, dorsal and ventral raphe, area of Forel, LC region, parabrachial nuclei, and NTS. The lateral septum and lateral habenula displayed no and very few VP fibers, respectively. No extrahypothalamic OXT neurons were found in the brain of this macaque monkey. Dense concentrations of OXT fibers were demonstrated in the amygdala, NTS, and marginal layer of the cervical spinal cord. No sexual dimorphism was found in this primate VP or OXT system. The results show a distribution of the central VP and OXT systems in this primate which is quite different from that in the rat. However, in various aspects it agrees with current data on the VP and OXT systems of the human brain. The present results suggest, therefore, that this monkey might serve as a better model for the human VP system than the rat.     

Efferent projections of the infralimbic cortex of the rat.

On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.     

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.