Projections of the dorsal raphe nucleus to the brainstem: PHA-L analysis in the rat

Early studies that used older tracing techniques reported exceedingly few projections from the dorsal raphe nucleus (DR) to the brainstem. The present report examined DR projections to the brainstem by use of the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). DR fibers were found to terminate relatively substantially in several structures of the midbrain, pons, and medulla. The following pontine and midbrain nuclei receive moderate to dense projections from the DR: pontomesencephalic central gray, mesencephalic reticular formation, pedunculopontine tegmental nucleus, medial and lateral parabrachial nuclei, nucleus pontis oralis, nucleus pontis caudalis, locus coeruleus, laterodorsal tegmental nucleus, and raphe nuclei, including the central linear nucleus, median raphe nucleus, and raphe pontis. The following nuclei of the medulla receive moderately dense projections from the DR: nucleus gigantocellularis, nucleus raphe magnus, nucleus raphe obscurus, facial nucleus, nucleus gigantocellularis-pars alpha, and the rostral ventrolateral medullary area. DR fibers project lightly to nucleus cuneiformis, nucleus prepositus hypoglossi, nucleus paragigantocellularis, nucleus reticularis ventralis, and hypoglossal nucleus. Some differences were observed in projections from rostral and caudal parts of the DR. The major difference was that fibers from the rostral DR distribute more widely and heavily than do those from the caudal DR to structures of the medulla, including raphe magnus and obscurus, nucleus gigantocellularis-pars alpha, nucleus paragigantocellularis, facial nucleus, and the rostral ventrolateral medullary area. A role for the dorsal raphe nucleus in several brainstem controlled functions is discussed, including REM sleep and its events, nociception, and sensory motor control. © Wiley-Liss, Inc.     

Cerebellothalamic projections in the rat: An autoradiographic and degeneration study

The purpose of this study was to determine the topographical organization of cerebellothalamic projections in the rat. Following stereotaxic injections of ³H-leucine or electrolytic lesions in the cerebellar nuclei, efferent fibers were observed to emerge from the cerebellum through two discrete routes. Fibers from the fastigial nucleus decussated within the cerebellum, formed the crossed ascending limb of the uncinate fasciculus, ascended in the dorsal part of the midbrain tegmentum, and entered the thalamus. Cerebellothalamic fibers from the interpositus and dentate nuclei coursed in the ipsilateral brachium conjuctivum, decussated in the caudal midbrain, and ascended to the thalamus via the crossed ascending limb of the brachium conjunctivum. Cerebellar terminations were observed in the intralaminar, lateral, and ventral tier thalamic nuclei as well as in the medial dorsal nucleus. Projections to the intralaminar nuclei were more pronounced from the dentate and posterior interpositus than from the anterior interpositus and fastigial nuclei. The lateral thalamic nuclei received a projection from the dentate and posterior interpositus nuclei while the fastigial nucleus projected to the medial dorsal nucleus. Within the rostral ventral tier nuclei fastigiothalamic terminations were localized in the medial parts of the ventral medial and ventral lateral nuclei, whereas dentatothalamic projections were concentrated in the lateral parts of the ventral medial nucleus and the medial half of the ventral lateral nucleus. Terminations from the posterior interpositus nucleus were observed ventrally and laterally within the caudal two-thirds of the ventral medial nucleus and throughout the ventral lateral nucleus, where they were densest in the lateral part of its lateral wing and within the central part of its cap. The anterior interpositus nucleus also projected to the central and lateral parts of the ventral lateral nucleus, but these terminations were considerably less dense than those from the posterior interpositus. A few fibers from the interpositus nuclei terminated in the medial part of the rostral pole of the ventral posterior nucleus. A prominent recrossing of cerebellothalamic fibers from the fastigial, posterior interpositus, and dentate nuclei occurred through the central medial nucleus of the internal medullary lamina. These terminated within the ipsilateral ventral lateral and intralaminar nuclei. These results show that each of the cerebellar nuclei project to the thalamus and that their terminations are topographically organized in the rostral ventral tier nuclei. The clustering of autoradiographic silver grains or terminal degeneration observed in the thalamic nuclei suggests a medial-to-lateral organization of this cerebellothalamic system.     

An autoradiographic study of projections ascending from the midbrain central gray, and from the region lateral to it, in the rat

Ascending projections from the midbrain central gray (CG) and from the region lateral to it were traced in the rat using tritiated amino acid autoradiography. Leucine or a cocktail of amino acids (leucine, proline, lysine, histidine, and tyrosine) were used as tracers. In addition to projections within the midbrain, ascending fibers follow three trajectories. The ventral projection passes through the ventral tegmental region of Tsai and the medial forebrain bundle to reach the hypothalamus, preoptic area, caudoputamen, substantia innominata, stria terminalis, and amygdala. There are labeled fibers in the diagonal bands of Broca and medial septum, and terminal labeling in the lateral septum, nucleus accumbens, olfactory tubercle, and frontal cortex. The dorsal periventricular projection terminates in the midline and intralaminar thalamic nuclei. The ventral periventricular projection follows the ventral component of the third ventricle into the hypothalamus, passing primarily through the dorsal hypothalamic area and labeling the rostral hypothalamus and preoptic area. Projections from the region lateral to the CG are similar, but exhibit stronger proximal, and weaker distal, projections. Rostral levels of the CG send heavier projections to the fields of Forel and the zona incerta, but fewer fibers through the supraoptic decussation, than do caudal levels. Ascending projections from the CG are both strong and widespread. Strong projections to the limbic system and the intralaminar thalamic nuclei provide an anatomical substrate for CG involvement in nociception and affective responses.     

Projections of the median raphe nucleus in the rat

No previous report in any species has examined comprehensively the projections of the median raphe (MR) nucleus with modern tracing techniques. The present report represents an in depth analysis of the projections of MR by use of the anterograde anatomical tracer Phaseolus vulgaris-leucoagglutinin. MR fibers descend along the midline within the brainstem and mainly ascend within the medial forebrain bundle in the forebrain. MR fibers distribute densely to the following brainstem/forebrain sites: caudal raphe nuclei, laterodorsal tegmental nucleus, dorsal raphe nucleus, interpeduncular nucleus, medial mammillary body, supramammillary nucleus, posterior nucleus and perifornical region of the hypothalamus, midline and intralaminar nuclei of thalamus, dopamine-containing cell region of medial zona incerta, lateral habenula, horizontal and vertical limbs of the diagonal band nuclei, medial septum, and hippocampal formation. Virtually all of these structures lie on or close to the midline, indicating that the MR represents a midline/para-midline system of projections. Overall, MR projections to the cortex are light. MR projects moderately to the perirhinal, entorhinal and frontal cortices, but sparingly to remaining regions of cortex. A comparison of MR with dorsal raphe (DR) projections (Vertes RP. 1991. J Comp Neurol 313:643-668) shows that these two major serotonin-containing cell groups of the midbrain distribute to essentially nonoverlapping regions of the forebrain; that is, the MR and DR project to complementary sites in the forebrain. A direct role for the MR in the desynchronization of the electroencephalographic activity of the hippocampus and its possible consequences for memory-associated functions of the hippocampus is discussed.     

Diencephalic projections from the pontine reticular formation: autoradiographic studies in the cat

Ascending projections to the diencephalon from the pontine reticular formation were studied in the cat by autoradiographic techniques. Projections from both rostral and caudal pontine regions ascend to the caudal diencephalon and divide into two components; a dorsal leaf terminates primarily in the thalamic intralaminar complex and a ventral leaf terminates in the subthalamic region. The relative densities of the two terminal regions vary with the injection site. Fibers originating in the caudal pons (nucleus reticularis pontis caudalis) terminate relatively heavily in the intralaminar nuclei of the dorsal thalamus, particularly the centre median, central lateral, central dorsal and paracentral nuclei, and also the dorsal medial nucleus. Relatively sparse termination occurs in the subthalamic region. In contrast, fibers from the rostral pons (nucleus reticularis pontis oralis) terminate relatively heavily in the subthalamic region, including the zona incerta, the fields of Forel, the ventral part of the thalamic reticular complex, and the lateral hypothalamus. Relatively sparse termination occurs in the dorsal thalamus, but includes the centre median, parafascicular, central lateral, paracentral and dorsal medial nuclei. These data are discussed with regard to reticular control of forebrain activity and the role of the classic dorsal and ventral components of ascending reticular projections.     

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.     

Periaqueductal gray matter projections to midline and intralaminar thalamic nuclei of the rat

The periaqueductal gray matter (PAG) projections to the intralaminar and midline thalamic nuclei were examined in rats. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in discrete regions of the PAG, and axonal labeling was examined in the thalamus. PHA-L was also placed into the dorsal raphe nuclei or nucleus of Darkschewitsch and interstitial nucleus of Cajal as controls. In a separate group of rats, the retrograde tracer cholera toxin beta-subunit (CTb) was injected into one of the intralaminar thalamic nuclei-lateral parafascicular, medial parafascicular, central lateral (CL), paracentral (PC), or central medial nucleus-or one of the midline thalamic nuclei-paraventricular (PVT), intermediodorsal (IMD), mediodorsal, paratenial, rhomboid (Rh), reuniens (Re), or caudal ventral medial (VMc) nucleus. The distribution of CTb labeled neurons in the PAG was then mapped. All PAG regions (the four columns of the caudal two-thirds of the PAG plus rostral PAG) and the precommissural nucleus projected to the rostral PVT, IMD, and CL. The ventrolateral, lateral, and rostral PAG provided additional inputs to most of the other intralaminar and midline thalamic nuclei. PAG inputs to the VMc originated from the rostral and ventrolateral PAG areas. In addition, the lateral and rostral PAG projected to the zona incerta. No evidence was found for a PAG input to the ventroposterior lateral parvicellular, ventroposterior medial parvicellular, caudal PC, oval paracentral, and reticular thalamic nuclei. PAG --> thalamic circuits may modulate autonomic-, nociceptive-, and behavior-related forebrain circuits associated with defense and emotional responses.     

Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study.

The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.     

PHA-L analysis of projections from the supramammillary nucleus in the rat.

The projections of the supramammillary nucleus (SUM) were examined in the rat by the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from SUM ascended through the forebrain within the medial forebrain bundle. SUM fibers were found to terminate heavily in the hippocampal formation, specifically within the granule cell layer and immediately adjoining molecular layer of the dentate gyrus. In addition, SUM fibers were shown to distribute densely to several structures with strong connections with the hippocampus, namely, the nucleus reunions of the thalamus, the medial and lateral septum, the entorhinal cortex, and the endopiriform nucleus. SUM fibers were also shown to project significantly to several additional subcortical and cortical sites. The subcortical sites were the dorsal raphe nucleus, the midbrain central gray, the fields of Forel/zona incerta, the dorsomedial hypothalamic area, midline/intralaminar nuclei of the thalamus (posterior paraventricular, rhomboid, central medial, intermediodorsal, and mediodorsal), the medial and lateral preoptic areas, the bed nucleus of the stria terminalis, the substantia innominata, the vertical limb of the diagonal band nucleus, and the claustrum. The cortical sites were the occipital, temporal, parietal, and frontal cortices. Some notable differences were observed in projections from the lateral as compared to the medial SUM. For example, fibers originating from the lateral SUM distributed heavily to the hippocampal formation and parts of the cortex, whereas those from the medial SUM projected sparsely to these two regions. The SUM projections to the hippocampal formation and associated structures may serve as the substrate for a SUM involvement in the generation of the theta rhythm of the hippocampus and the gating of information flow through the hippocampal formation.     

Brainstem projections to midline and intralaminar thalamic nuclei of the rat

The projections from the brainstem to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin beta -subunit (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus: the lateral parafascicular, medial parafascicular, central lateral, paracentral, oval paracentral, and central medial nuclei; in the midline thalamic nuclei-the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, and submedius nuclei; and, in the anteroventral, parvicellular part of the ventral posterior, and caudal ventral medial nuclei. The retrograde cell body labeling pattern within the brainstem nuclei was then analyzed. Nearly every thalamic site received a projection from the deep mesencephalic reticular, pedunculopontine tegmental, dorsal raphe, median raphe, laterodorsal tegmental, and locus coeruleus nuclei. Most intralaminar thalamic sites were also innervated by unique combinations of medullary and pontine reticular formation nuclei such as the subnucleus reticularis dorsalis, gigantocellular, dorsal paragigantocellular, lateral, parvicellular, caudal pontine, ventral pontine, and oral pontine reticular nuclei; the dorsomedial tegmental, subpeduncular tegmental, and ventral tegmental areas; and, the central tegmental field. In addition, most intralaminar injections resulted in retrograde cell body labeling in the substantia nigra, nucleus Darkschewitsch, interstitial nucleus of Cajal, and cuneiform nucleus. Details concerning the pathways from the spinal trigeminal, nucleus tractus solitarius, raphe magnus, raphe pallidus, and the rostral and caudal linear raphe nuclei to subsets of midline and intralaminar thalamic sites are discussed in the text. The discussion focuses on brainstem-thalamic pathways that are likely involved in arousal, somatosensory, and visceral functions.     

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.     

Horseradish peroxidase tracing of the lateral habenular-midbrain raphe nuclei connections in the rat

Connections of the habenular complex to the nuclei of the midline in the midbrain (interpeduncularis, medianus raphe, and dorsalis raphe) have been studied classically by anterograde degeneration in the monkey, the cat, and marsupials. Passing fibers from the medial septal nucleus and lateral preoptic area, however, have also been demonstrated which can complicate interpretation of these results. In this paper the habenular projections were studied in the rat by the retrograde axonal transport of horseradish peroxidase (HRP). After HRP injections in the medianus raphe nucleus labelled neurons appeared in the lateral habenular nucleus and parafascicular nucleus. Labelled neurons were also found in the lateral habenular nucleus after injections in either the dorsalis raphe nucleus or the caudal central gray substance. The habenular projections were always bilateral. There were no labelled neurons in the medial habenular nucleus after HRP injections in the medianus raphe nucleus, dorsalis raphe nucleus, or central gray. These data stress the lateral habenular influences upon the raphe nuclei, especially on the dorsalis raphe neurons which have usually been thought of as functionally related to other brainstem structures. The present results suggest also that in the rat the lateral habenular nucleus might be the link between basal forbrain inputs and the limbic midbrain area. Thus, the raphe nuclei of the midbrain appear to be crucial regions for integrating two descending circuits: first, a limbic (through septum) circuit, and, second, a basal forebrain (through lateral habenular-preoptic area) circuit.     

The efferent projections of the periaqueductal gray in the rat: A Phaseolus vulgaris-leucoagglutinin study. I. Ascending projections

This study has examined the ascending projections of the periaqueductal gray in the rat. Injections of Phaseolus vulgaris-leucoagglutinin were placed in the dorsolateral or ventrolateral subregions, at rostral or caudal sites. From either region, fibers ascended via two bundles. The periventricular bundle ascended in the periaqueductal and periventricular gray matter. At the posterior commissure level, this bundle divided into a dorsal component that terminated in the intralaminar and midline thalamic nuclei, and a ventral component that supplied the hypothalamus. The ventral bundle formed in the deep mesencephalic reticular formation and supplied the ventral tegmental area, substantia nigra pars compacta, and the retrorubral field. The remaining fibers were incorporated into the medial forebrain bundle. These supplied the lateral hypothalamus and forebrain structures, including the preoptic area, the nuclei of the diagonal band, and the lateral division of the bed nucleus of the stria terminalis. The dorsolateral subregion preferentially innervated the centrolateral and paraventricular thalamic nuclei and the anterior hypothalamic area. The ventrolateral subregion preferentially innervated the parafascicular and central medial thalamic nuclei, the lateral hypothalamic area, and the lateral division of the bed nucleus of the stria terminalis. Although the dorsolateral and ventrolateral subregions gave rise to differential projections, the projections from both the rostral and caudal parts of either subregion were similar. This suggests that the dorsolateral and ventrolateral subregions are organized into longitudinal columns that extend throughout the length of the periaqueductal gray. These columns may correspond to those demonstrated in recent physiological studies. © 1995 Willy-Liss, Inc.     

Efferent connections of the centromedian and parafascicular thalamic nuclei: an autoradiographic investigation in the cat

The efferent projections of the centromedian and parafascicular (CM-Pf) thalamic nuclear complex were analyzed by the autoradiographic method. Our findings show that the CM-Pf complex projects in a topographic manner to specific regions of the rostral cortex. These fibers distribute primarily to cortical layers I and III; however, the projection to layer I is more extensive. Following an injection into the rostral portion of the CM-Pf complex, label is found within the lateral rostral cortex, particularly within the presylvian, anterior ectosylvian, and anterior lateral sulci, and within the rostral medial cortex where label is present within the cruciate and anterior splenial sulci and anterior cingulate gyrus. An injection into the caudal dorsal portion of the CM-Pf complex results in label within the more ventral portions of the rostral lateral cortex where it is present within the anterior sylvian gyrus, presylvian regions, and gyrus proreus; and within the rostral medial cortex, where it is present within the rostral cingulate gyrus, and within the cruciate sulcus, and an extensive region ventral to the cruciate sulcus which includes the anterior limbic area. Injections into the caudal ventral portion of the CM-Pf complex result in virtually no cortical label, although a few labeled fibers are found in the subcortical white matter. The subcortical projection from the CM-Pf complex terminates within the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, zona incerta, fields of Forel, hypothalamus, thalamic reticular nucleus, and rostral intralaminar nuclei. Prominent silver grain aggregates are also present within the ventral lateral, ventral anterior, ventral medial, and lateral posterior nuclei, and ventrobasal complex. The aggregates in the thalamus appear to be fibers of passage, but whether these are also terminals cannot be determined with the techniques used in the present study.     

Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum

The organization of the thalamic projections to the ventral striatum in the rat was studied by placing injections of the retrograde tracer cholera toxin subunit B in the ventral striatum and small deposits of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in individual midline and intralaminar thalamic nuclei. In order to provide a complete map of the midline and intralaminar thalamostriatal projections, PHA-L injections were also made in those parts of the intralaminar nuclei that project to the dorsal striatum. The relationship of thalamic afferent fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin immunohistochemistry. The various midline and intralaminar thalamic nuclei project to longitudinally oriented striatal sectors. The paraventricular thalamic nucleus sends most of its fibres to medial parts of the nucleus accumbens and the olfactory tubercle, whereas smaller contingents of fibres terminate in the lateral part of the nucleus accumbens and the most ventral, medial, and caudal parts of the caudate-putamen complex. The projections of the parataenial nucleus are directed towards central and ventral parts of the nucleus accumbens and intermediate mediolateral parts of the olfactory tubercle. The intermediodorsal nucleus projects to lateral parts of the nucleus accumbens and the olfactory tubercle and to ventral parts of the caudate-putamen. The projection of the rhomboid nucleus is restricted to the rostrolateral extreme of the striatum. A diffuse projection to the ventral striatum arises from neurons ventral and caudal to the nucleus reuniens rather than from cells inside the nucleus. Fibres from the central medial nucleus terminate centrally and dorsolaterally in the rostral part of the nucleus accumbens and medially in the caudate-putamen. Successively more lateral positions in the caudate-putamen are occupied by fibres from the paracentral and central lateral nuclei, respectively. The lateral part of the parafascicular nucleus projects to the most lateral part of the caudate-putamen, whereas projections from the medial part of this nucleus terminate in the medial part of the caudate-putamen and in the dorsolateral part of the nucleus accumbens. Furthermore, a rostral to caudal gradient in a midline or intralaminar nucleus corresponds to a dorsal to ventral and rostral to caudal gradient in the striatum. In the ventral striatum, thalamic afferent fibres in the "shell" region of the nucleus accumbens avoid areas of high cell density and weak enkephalin immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Efferents from medial basal forebrain and hypothalamus in the rat. I. An autoradiographic study of the medial preoptic area.

Efferent projections from the medial and periventricular preoptic area, bed nucleus of the stria terminalis and nuclei of the diagonal band were traced using tritiated amino acid autoradiography in albino rats. Medial and periventricular preoptic area efferents were not restricted to short-axon projections. Ascending projections from the medial preoptic area (mPOA) were traced through the diagonal band into the septum. Descending mPOA axons coursed in the medial parts of the medial forebrain bundle. Projections to most hypothalamic nuclei, including the arcuate nucleus and median eminence, were observed. In the midbrain, mPOA efferents were distributed in the central grey, raphe nuclei, ventral tegmental area and reticular formation. Projections from the mPOA were also observed to the amygdala through the stria terminalis, to the lateral habenula through the stria medullaris, and to the periventricular thalamus. Axons of the most medial and periventricular preoptic area (pvPOA) neurons had a distribution similar to more lateral mPOA neurons but their longest-axoned projections were weaker. The pvPOA did not send axons through the stria medullaris but did project more heavily than the more lateral mPOA to the arcuate nucleus and median eminence. Projections from the bed nucleus of the stria terminalis (nST) were in most respects similar to those from the medial preoptic area, with the major addition of a projection to the accessory olfactory bulb. The nuclei of the diagonal band of Broca (nDBB) gave a different pattern of projections than mPOA or nST, projecting, for instance, to the medial septum and hippocampus. Descending nDBB efferents ran in the ventral portion of the medial forebrain bundle. Among hypothalamic cell groups, only the medial mammillary nuclei received nDBB projections. nDBB efferents also distributed in the medial and lateral habenular nuclei and the mediodorsal thalamic nucleus.     

Organization of subcortical pathways for sensory projections to the limbic cortex. I. Subcortical projections to the medial limbic cortex in the rat

Subcortical afferent projections to the medial limbic cortex were examined in the rat by the use of retrograde axonal transport of horseradish peroxidase. Small iontophoretic injections of horseradish peroxidase were placed at various locations within the dorsal and ventral cingulate areas, the dorsal agranular and ventral granular divisions of the retrosplenial cortex and the presubiculum. Somata of afferent neurons in the thalamus and basal forebrain were identified by retrograde labeling. Each of the anterior thalamic nuclei was found to project to several limbic cortical areas, although not with equal density. The anterior dorsal nucleus projects primarily to the presubiculum and ventral retrosplenial cortex; the anterior ventral nucleus projects to the retrosplenial cortex and the presubiculum with apparently similar densities; and the anterior medial nucleus projects primarily to the cingulate areas. The projections from the lateral dorsal nucleus to these limbic cortical areas are organized in a loose topographic fashion. The projection to the presubiculum originates in the most dorsal portion of the lateral dorsal nucleus. The projection to the ventral retrosplenial cortex originates in rostral and medial portions of the nucleus, whereas afferents to the dorsal retrosplenial cortex originate in caudal portions of the lateral dorsal nucleus. The projection to the cingulate originates in the ventral portion of the lateral dorsal nucleus. Other projections from the thalamus originate in the intralaminar and midline nuclei, including the central lateral, central dorsal, central medial, paracentral, reuniens, and paraventricular nuclei, and the ventral medial and ventral anterior nuclei. In addition, projections to the medial limbic cortex from the basal forebrain originate in cells of the nucleus of the diagonal band. Projections to the presubiculum also originate in the medial septum. These results are discussed in regard to convergence of sensory and nonsensory information projecting to the limbic cortex and the types of visual and other sensory information that may be relayed to the limbic cortex by these projections.     

An autoradiographic study of the projections of the central nucleus of the monkey amygdala

The efferent connections of the central nucleus of the monkey amygdala have been studied using the autoradiographic method for tracing axonal projections. Small injections of 3H-amino-acids which are largely confined to the central nucleus lead to the labeling of several brainstem nuclei as far caudally as the spinomedullary junction. Specifically, in the forebrain, the central nucleus projects heavily to the bed nucleus of the stria terminalis, the basal nucleus of Meynert, the nucleus of the horizontal limb of the diagonal band, and more lightly to the substantia innominata and the preoptic area. In the hypothalamus, label is found over the dorsomedial nucleus, the perifornical region, the lateral hypothalamus, the supramammillary area, and most heavily in the paramammillary nucleus. In the thalamus, all components of the nucleus centralis medialis and the nucleus reuniens receive fibers from the central nucleus and there is a light projection to the medial pulvinar nucleus. In the mesencephalon, there is heavy labeling dorsal to the substantia nigra ad over the peripeduncular nucleus and lighter labeling within the substantia nigra pars compacta and the ventral tegmental area; the midbrain central gray is also labeled. More caudally, fibers from the central nucleus travel in the lateral tegmental reticular fields and contribute collaterals to the raphe nuclei, the cuneiform nucleus, and the central gray substance. Perhaps one of the heaviest terminal zones is the parabrachial region of the pons, both the lateral and the medial nuclei of which receive a prominent central nucleus projection. Only the ventral aspect of the adjacent locus coeruleus appears to receive a substantial input, but there is labeling also over the area of the nucleus subcoeruleus. Finally, there is heavy labeling around the dorsal motor nucleus of the vagus and over the parvocellular component of the nucleus of the solitary tract. A number of intra-amygdaloid connections between the basal and lateral nuclei of the amygdala and the central nucleus are also described. The present findings, taken together with recently reported widespread projections from the temporal association cortex to the amygdala, point out a potentially trisynaptic route between neocortical association regions and a variety of brainstem nuclei, many of which are related to autonomic function.     

The thalamostriatal projection in the cat

The organization of the projections from the intralaminar and other thalamic nuclei to the caudate nucleus (CD), putamen (PU), nucleus accumbens (Acc), and olfactory tubercle (TO) were examined in the cat by autoradiography after deposits of ³H-amino acids in individual thalamic nuclei and by retrograde cell labeling after intrastriatal deposits of wheat-germ-conjugated horseradish peroxidase. All of the rostral intralaminar nuclei, here considered to include the central lateral (CL), paracentral (PC), central medial (CeM), and rhomboid nuclei (Rh), project to the striatum. Projections closely associated with those of the rostral intralaminar group arise from cells of the paraventricular nucleus (PV) and a region lateral to the stria medullaris. These nuclei, which roughly form a ring around the mediodorsal nucleus, project in a highly particular, but loosely arranged topographic pattern to all parts of the striatum. The medially located cells in Rh, PV, and those alongside the stria medullaris project mainly to medial parts of Acc and CD; the dorsolaterally located cells of CL project mainly to the dorsolateral parts of CD and PU; cells in PC and CeM project to progressively more ventral and medial parts of CD and PU, and the lateral part of Acc. Superimposed on this projection from the rostral intralaminar region is the projection from the caudal intralaminar group including the centromedian (CM), parafascicular (PF), and subparafascicular nuclei (subPF). Together these nuclei project in a loosely but specifically organized topography to the entire striatum. The lateral and dorsal parts of CD and PU receive fibers mainly from CM. Ventral and medial parts of CD and PU and Acc receive fibers mainly from PF; TO receives fibers from subPF and the ventral part of PF. Several nuclei in the lateral nuclear mass of the thalamus also project to particular parts of the striatum. Thus, cells in the rostromedial part of the ventral anterior nucleus project to the head of CD and some cells in the rostral part of the ventromedial nucleus project to the head of CD and to PU. Several cells scattered in the lateral posterior complex project to lateral parts of the head of CD, and cells in the rostral extension of the medial subdivision of the posterior nuclear complex project to lateral parts of the head and body of CD. Finally, several cells of the paratenial nucleus project selectively to Acc. These data provide a detailed map of the total thalamostriatal projection in the cat and, hence, form a basis for more specific functional questions about this poorly understood system.