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

The descending projections of the periaqueductal gray (PAG) have been studied in the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. The tracer was injected into the dorsolateral or ventrolateral subdivisions of the PAG at rostral or caudal sites. It was found that the patterns of the descending projections of the rostral and caudal parts of the dorsolateral PAG were the same and that the patterns of the descending projections of the rostral and caudal parts of the ventrolateral PAG were the same. However, the patterns of projections of the dorsolateral and ventrolateral PAG subregions were substantially different. These results suggest that the dorsolateral and ventrolateral parts of the PAG are organized into longitudinal columns that extend throughout the length of the PAG. The axons of PAG neurons descended through the pons and medulla via two routes. A small fiber bundle was present in the periaqueductal gray and in the periventricular area. This bundle distributed fibers and terminals locally within the periaqueductal gray and in the locus coeruleus and Barrington's nucleus. A larger bundle had a diffuse arrangement in the pontine reticular formation, however, and it had a more restricted distribution in the medulla, where it occupied a position dorsolateral to the pyramid. This bundle supplied structures in the pontine and medullary tegmentum. The dorsolateral column preferentially supplied the locus coeruleus, subcoeruleus, the gigantocellular nucleus pars alpha, the rostral part of the paragigantocellular nucleus, and the region of the A5 noradrenergic cell group. The ventrolateral column preferentially supplied the nucleus raphe magnus, the caudal part of the lateral paragigantocellular nucleus, and the rostroventrolateral reticular nucleus. © 1995 Willy-Liss, Inc.     

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.     

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.     

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.     

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.     

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

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

Projections from the rhomboid nucleus of the bed nuclei of the stria terminalis: implications for cerebral hemisphere regulation of ingestive behaviors

The basic organization of an exceptionally complex pattern of axonal projections from one distinct cell group of the bed nuclei of the stria terminalis, the rhomboid nucleus (BSTrh), was analyzed with the PHAL anterograde tract-tracing method in rats. Brain areas that receive a strong to moderate input from the BSTrh fall into nine general categories: central autonomic control network (central amygdalar nucleus, descending hypothalamic paraventricular nucleus, parasubthalamic nucleus and dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, lateral parabrachial nucleus and caudal nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and salivatory nuclei), gustatory system (rostral nucleus of the solitary tract and medial parabrachial nucleus), neuroendocrine system (periventricular and paraventricular hypothalamic nuclei, hypothalamic visceromotor pattern generator network), orofaciopharyngeal motor control (rostral tip of the dorsal nucleus ambiguus, parvicellular reticular nucleus, retrorubral area, and lateral mesencephalic reticular nucleus), respiratory control (lateral nucleus of the solitary tract), locomotor or exploratory behavior control and reward prediction (nucleus accumbens, substantia innominata, and ventral tegmental area), ingestive behavior control (descending paraventricular nucleus and dorsal lateral hypothalamic area), thalamocortical feedback loops (medial-midline-intralaminar thalamus), and behavioral state control (dorsal raphé and locus coeruleus). Its pattern of axonal projections and its position in the basal telencephalon suggest that the BSTrh is part of a striatopallidal differentiation involved in modulating the expression of ingestive behaviors, although it may have other functions as well.     

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

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

Afferent connections to the lateral hypothalamus: A horseradish peroxidase study in the rat

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the mid lateral hypothalamus (LH) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal or sagittal planes into 30–50 μm sections. Sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that a significant number of afferent connections to the LH originate in the olfactory and accumbens nuclei, pyriform cortex, olfactory tracts, magnocellular and medial preoptic and anterior hypothalamic regions, stria terminalis, stria hypothalamic tract, diagonal tract of Broca, caudate-putamen and globus pallidus, internal capsule, lateral septal nuclei, lateral preoptic area and anterior medial forebrain bundle, the various amygdaloid nuclei, zona incerta, perifornical region, dorsal and ventral medial hypothalamic areas, supraoptic, paraventricular and periventricular nuclei, posterior hypothalamus and medial forebrain bundle, ventral thalamic nuclei, the fields of Forel, arcuate and mammillary nuclei, adjacent to the fasciculus retroflexus, in the ventral tegmental area of Tsai, interpeduncular nucleus, substantia nigra, mesencephalic reticular formation, periaqueductal gray, locus coeruleus and parabrachial region. Results are discussed in terms of previous anatomical and neurophysiological data, probable pathways, and the function of LH neurons.     

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.     

Organization of inputs to the dorsomedial nucleus of the hypothalamus: a reexamination with Fluorogold and PHAL in the rat

Possible inputs to the DMH were studied first using the fluorescent retrograde tracer Fluorogold, and identified cell groups were then injected with the anterograde tracer PHAL to examine the distribution of labeled axons in and around the DMH. From this work, we conclude that the majority of inputs to the DMH arise in the hypothalamus, although there are a few significant projections from the telencephalon and brainstem. With few exceptions, each major nucleus and area of the hypothalamus provides inputs to the DMH. Telencephalic inputs arise mainly in the ventral subiculum, infralimbic area of the prefrontal cortex, lateral septal nucleus, and bed nuclei of the stria terminalis. The majority of brainstem inputs arise in the periaqueductal gray, parabrachial nucleus, and ventrolateral medulla. In addition, it now seems clear that inputs to the DMH use only a few discrete pathways. Descending inputs course through a periventricular pathway through the hypothalamic periventricular zone, a medial pathway that follows the medial corticohypothalamic tract, and a lateral pathway traveling through medial parts of the medial forebrain bundle. Ascending inputs arrive through a midbrain periventricular pathway that travels adjacent to the cerebral aqueduct in the periaqueductal gray, and through a brainstem lateral pathway that travels through central and ventral midbrain tegmental fields and enters the hypothalamus, and then the DMH from more lateral parts of the medial forebrain bundle. The results are discussed in relation to evidence for involvement of the DMH in ingestive behavior, and diurnal and stress-induced corticosterone secretion.     

Efferent projections from the lateral hypothalamus in the guinea pig: An autoradiographic study

Autoradiography was employed to investigate the efferent projections from the lateral hypothalamus in the guinea pig. Lateral hypothalamic axons were traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced to the lateral preoptic area, diagonal band of Broca, and septal nuclei. Posterior projections included the ventral tegmental area of Tsai, central gray matter and the reticular formation throughout the brain stem. Laterally, the lateral hypothalamic efferents were found in the stria terminalis, amygdala and globus pallidus. Dorsally, the lateral hypothalamic axons projected to the midline nuclei of the thalamus and bilaterally to the lateral habenular nuclei. Projections to the medial hypothalamus included a labeled fiber bundle to the internal layer of the median eminence and to the posterior lobe of the pituitary gland. Labeled fibers and diffuse label were also found in some areas contralateral to the injection site.     

Projections of the parabrachial nucleus in the pigeon (Columba livia).

The ascending and descending projections of the parabrachial nuclear complex in the pigeon have been charted with autoradiographic and histochemical (WGA-HRP) techniques. The ascending projections originate from a group of subnuclei surrounding various components of the brachium conjunctivum, namely, the superficial lateral, dorsolateral, dorsomedial, and ventromedial subnuclei. The projections are predominantly ipsilateral and travel in the quintofrontal tract. They are primarily to the medial and lateral hypothalamus (including the periventricular nucleus and the strata cellulare internum and externum), certain dorsal thalamic nuclei, the nucleus of the pallial commissure, the bed nucleus of the stria terminalis, the ventral paleostriatum, the olfactory tubercle, the nucleus accumbens, and a dorsolateral nucleus of the posterior archistriatum. There are weaker or more diffuse projections to the rostral locus coeruleus (cell group A8), the compact portion of the pedunculopontine tegmental nucleus, the central grey and intercollicular region, the ventral area of Tsai, the medial spiriform nucleus, the nucleus subrotundus, the anterior preoptic area, and the diagonal band of Broca. The parabrachial subnuclei have partially differential projections to these targets, some of which also receive projections from the nucleus of the solitary tract (Arends, Wild, and Zeigler: J. Comp. Neurol. 278:405-429, '88). Most of the targets, particularly those in the basal forebrain (viz., the periventricular nucleus and the strata cellulare internum and externum of the hypothalamus, the bed nucleus of the stria terminalis, and its lateral extension into the ventral paleostriatum, which may be comparable with the substantia innominata), have reciprocal connections with the parabrachial and solitary tract subnuclei and therefore may be said to compose parts of a "visceral forebrain system" analogous to that described in the rat (Van der Kooy et al: J. Comp. Neurol. 224:1-24, '84). The descending projections to the lower brainstem arise in large part from a ventrolateral subnucleus that may be comparable with the K?lliker-Fuse nucleus of mammals. They are mainly to the ventrolateral medulla, nucleus ambiguus, and massively to the hypoglossal nucleus, particularly its tracheosyringeal portion. These projections are therefore likely to be importantly involved in the control of vocalization and respiration (Wild and Arends: Brain Res. 407:191-194, '87). Some of these results have been presented in abstract form (Wild, Arends, and Zeigler: Soc. Neurosci. Abst. 13:308, '87).     

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.     

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.     

Connections of the precommissural nucleus.

The connections of the precomissural nucleus (PRC) have been examined with anterograde and retrograde axonal tracing methods in the rat. Experiments with cholera toxin B subunit (CTb) indicate that the PRC shares a number of common afferent sources with the dorsolateral periaqueductal gray (PAG). Thus, we have shown that the nucleus receives substantial inputs from the prefrontal cortex, specific domains of the rostral part of the lateral septal nucleus, rostral zona incerta, perifornical region, anterior hypothalamic nucleus, ventromedial hypothalamic nucleus, dorsal premammillary nucleus, medial regions of the intermediate and deep layers of the superior colliculus, and cuneiform nucleus. Moreover, the PRC also receives inputs from several PAG regions and from neural sites involved in the control of attentive or motivational state, including the laterodorsal tegemental nucleus and the ventral tegmental area. The efferent projections of the PRC were analyzed by using the Phaseolus vulgaris-leucoagglutinin (PHA-L) method. Notably, the PRC presents a projection pattern that resembles in many ways the pattern described previously for the rostral dorsolateral PAG in addition to projections to a number of targets that also are innervated by neighboring pretectal nuclei, including the rostrodorsomedial part of the lateral dorsal thalamic nucleus, the ventral part of the lateral geniculate complex, the medial pretectal nucleus, the nucleus of the posterior commissure, and the ventrolateral part of the subcuneiform reticular nucleus. Overall, the results suggest that the PRC might be viewed as a rostral component of the PAG, and the possible functional significance of the nucleus is discussed in terms of its connections.     

Limbic connections to the lateral preoptic area: a horseradish peroxidase study in the rat

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the lateral preoptic area (LPA) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal plane into 50 microns sections. Alternate sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that there are a significant number of limbic efferent connections to the LPA. Afferents to the LPA originate in the prefrontal corex, nucleus accumbens, diagonal band and olfactory structures, lateral and medial septum, stria hypothalamic tract and stria terminalis, the magnocellular and medial preoptic nuclei, along the extent of the medial forebrain bundle in the LPA and LH, anterior and basolateral amygdala, ventromedial caudate-putamen, stria medullaris and lateral habenula, the stellatocellular-periventricular, ventromedial, arcuate and anterior hypothalamic nuclei, the perifornical area, zona incerta, ventral medial thalamic area, ventral tegmental area of Tsai, interpeduncular nucleus, reticular zone of the substantia nigra, mesencephalic periaqueductal gray and reticular formation, all aspects of the raphe nuclei and the locus coeruleus. Results are discussed in terms of known anatomical and neurophysiological data and the similar limbic inputs observed for lateral hypothalamic neurons which are found along the extent of the medial forebrain bundle.     

Efferent connections of the dorsomedial thalamic nuclei of the domestic chick (Gallus domesticus)

Small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin were placed in the thalamic anterior dorsomedial nucleus (DMA) of domestic chicks. The projections of the DMA covered the rostrobasal forebrain, ventral paleostriatum, nucleus accumbens, septal nuclei, Wulst, hyperstriatum ventrale, neostriatal areas, archistriatal subdivisions, dorsolateral corticoid area, numerous hypothalamic nuclei, and dorsal thalamic nuclei. The rostral DMA projects preferentially on the hypothalamus, whereas the caudal part is connected mainly to the dorsal thalamus. The DMA is also connected to the periaqueductal gray, deep tectum opticum, intercollicular nucleus, ventral tegmental area, substantia nigra, locus coeruleus, dorsal lateral mesencephalic nucleus, lateral reticular formation, nucleus papillioformis, and vestibular and cranial nerve nuclei. This pattern of connectivity is likely to reflect an important role of the avian DMA in the regulation of attention and arousal, memory formation, fear responses, affective components of pain, and hormonally mediated behaviors.     

Amygdaloid and pontine projections to the ventromedial nucleus of the hypothalamus

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