Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and exerts strong excitatory actions on the hippocampus and medial prefrontal cortex. Although RE projections to the hippocampus have been well documented, no study using modern tracers has examined the totality of RE projections. With the anterograde anatomical tracer Phaseolus vulgaris leuccoagglutinin, we examined the efferent projections of RE as well as those of the rhomboid nucleus (RH) located dorsal to RE. Control injections were made in the central medial nucleus (CEM) of the thalamus. We showed that the output of RE is almost entirely directed to the hippocampus and "limbic" cortical structures. Specifically, RE projects strongly to the medial frontal polar, anterior piriform, medial and ventral orbital, anterior cingulate, prelimbic, infralimbic, insular, perirhinal, and entorhinal cortices as well as to CA1, dorsal and ventral subiculum, and parasubiculum of the hippocampus. RH distributes more widely than RE, that is, to several RE targets but also significantly to regions of motor, somatosensory, posterior parietal, retrosplenial, temporal, and occipital cortices; to nucleus accumbens; and to the basolateral nucleus of amygdala. The ventral midline thalamus is positioned to exert significant control over fairly widespread regions of the cortex (limbic, sensory, motor), hippocampus, dorsal and ventral striatum, and basal nuclei of the amygdala, possibly to coordinate limbic and sensorimotor functions. We suggest that RE/RH may represent an important conduit in the exchange of information between subcortical-cortical and cortical-cortical limbic structures potentially involved in the selection of appropriate responses to specific and changing sets of environmental conditions.     

Projections of the medial orbital and ventral orbital cortex in the rat

The medial orbital (MO) and ventral orbital (VO) cortices are prominent divisions of the orbitomedial prefrontal cortex. To our knowledge, no previous report in the rat has comprehensively described the projections of MO and VO. By using the anterograde tracer Phaseolus vulgaris leucoagglutinin and the retrograde tracer Fluoro-Gold, we examined the efferent projections of MO and VO in the rat. Although MO and VO projections overlap, MO distributes more widely throughout the brain, particularly to limbic structures, than does VO. The main cortical targets of MO were the orbital, ventral medial prefrontal (mPFC), agranular insular, piriform, retrosplenial, and parahippocampal cortices. The main subcortical targets of MO were the medial striatum, olfactory tubercle, claustrum, nucleus accumbens, septum, substantia innominata, lateral preoptic area, and diagonal band nuclei of the basal forebrain; central, medial, cortical, and basal nuclei of amygdala; paratenial, mediodorsal, and reuniens nuclei of the thalamus; posterior, supramammillary, and lateral nuclei of the hypothalamus; and periaqueductal gray, ventral tegmental area, substantia nigra, dorsal and median raphe, laterodorsal tegmental, and incertus nuclei of the brainstem. By comparison, VO distributes to some of these same sites, notably to the striatum, but lacks projections to parts of limbic cortex, to nucleus accumbens, and to the amygdala. VO distributes much more strongly, however, than MO to the medial (frontal) agranular, anterior cingulate, sensorimotor, posterior parietal, lateral agranular retrosplenial, and temporal association cortices. The patterns of MO projections are similar to those of the mPFC, whereas the projections of VO overlap with those of the ventrolateral orbital cortex (VLO). This suggests that MO serves functions comparable to those of the mPFC, such as goal-directed behavior, and VO performs functions similar to VLO such as directed attention. MO/VO may also serve as a link between lateral orbital and medial prefrontal cortices.     

Differential projections of the infralimbic and prelimbic cortex in the rat

The medial prefrontal cortex has been associated with diverse functions including attentional processes, visceromotor activity, decision-making, goal-directed behavior, and working memory. The present report compares and contrasts projections from the infralimbic (IL) and prelimbic (PL) cortices in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris-leucoagglutinin. With the exception of common projections to parts of the orbitomedial prefrontal cortex, olfactory forebrain, and midline thalamus, PL and IL distribute very differently throughout the brain. Main projection sites of IL are: 1) the lateral septum, bed nucleus of stria terminalis, medial and lateral preoptic nuclei, substantia innominata, and endopiriform nuclei of the basal forebrain; 2) the medial, basomedial, central, and cortical nuclei of amygdala; 3) the dorsomedial, lateral, perifornical, posterior, and supramammillary nuclei of hypothalamus; and 4) the parabrachial and solitary nuclei of the brainstem. By contrast, PL projects at best sparingly to each of these structures. Main projection sites of PL are: the agranular insular cortex, claustrum, nucleus accumbens, olfactory tubercle, the paraventricular, mediodorsal, and reuniens nuclei of thalamus, the capsular part of the central nucleus and the basolateral nucleus of amygdala, and the dorsal and median raphe nuclei of the brainstem. As discussed herein, the pattern of IL projections is consistent with a role for IL in the control of visceral/autonomic activity homologous to the orbitomedial prefrontal cortex of primates, whereas those of PL are consistent with a role for PL in limbic-cognitive functions homologous to the dorsolateral prefrontal cortex of primates.     

Nucleus reuniens of the midline thalamus: link between the medial prefrontal cortex and the hippocampus

The medial prefrontal cortex and the hippocampus serve well recognized roles in memory processing. The hippocampus projects densely to, and exerts strong excitatory actions on, the medial prefrontal cortex. Interestingly, the medial prefrontal cortex, in rats and other species, has no direct return projections to the hippocampus, and few projections to parahippocampal structures including the entorhinal cortex. It is well established that the nucleus reuniens of the midline thalamus is the major source of thalamic afferents to the hippocampus. Since the medial prefrontal cortex also distributes to nucleus reuniens, we examined medial prefrontal connections with populations of nucleus reuniens neurons projecting to hippocampus. We used a combined anterograde and retrograde tracing procedure at the light and electron microscopic levels. Specifically, we made Phaseolus vulgaris-leuccoagglutinin (PHA-L) injections into the medial prefrontal cortex and Fluorogold injections into the hippocampus (CA1/subiculum) and examined termination patterns of anterogradely PHA-L labeled fibers on retrogradely FG labeled cells of nucleus reuniens. At the light microscopic level, we showed that fibers from the medial prefrontal cortex form multiple putative synaptic contacts with dendrites of hippocampally projecting neurons throughout the extent of nucleus reuniens. At ultrastructural level, we showed that medial prefrontal cortical fibers form asymmetric contacts predominantly with dendritic shafts of hippocampally projecting reuniens cells. These findings indicate that nucleus reuniens represents a critical link between the medial prefrontal cortex and the hippocampus. We discuss the possibility that nucleus reuniens gates the flow of information between the medial prefrontal cortex and hippocampus dependent upon attentive/arousal states of the organism.     

Organization of cortical and subcortical projections to medial prefrontal cortex in the cat

We have analyzed the cortical and subcortical afferent connections of the medial prefrontal cortex (MPF) in the cat with the specific aim of characterizing subregional variations of afferent connectivity. Thirteen tracer deposits were placed at restricted loci within a cortical district extending from the proreal to the subgenual gyrus. The distribution throughout the forebrain of retrogradely labeled neurons was then analyzed. Within the thalamus, retrogradely labeled neurons were most numerous in the mediodorsal nucleus and in the ventral complex. The projection from each region exhibited continuous topography such that more medial thalamic neurons were labeled by tracer from more ventral and posterior cortical deposits. Marked retrograde labeling without any sign of topographic order occurred in a narrow medioventral sector of the lateroposterior nucleus. Several additional thalamic nuclei contained small numbers of labeled neurons. In a subset of nuclei closely affiliated with the limbic system (the parataenial, paraventricular, reuniens, and basal ventromedial nuclei), retrograde labeling occurred exclusively after deposits at extremely ventral and posterior cortical sites. Within the amygdala, retrogradely labeled neurons occupied the anterior basomedial nucleus, the posterior basolateral nucleus, and a narrow strip of the lateral nucleus immediately adjoining the basolateral nucleus. The number of labeled neurons was greater after more ventral deposits. Very ventral deposits resulted in extensive labeling of the cortical amygdala. Within the cerebral cortex, the distribution of labeled neurons depended on the location of the tracer deposit. Comparatively dorsal deposits produced prominent retrograde transport to the anterior and posterior cingulate areas, to the agranular insula, and to lateral prefrontal cortex. Comparatively ventral deposits gave rise to prominent labeling of the hippocampal subiculum, various parahippocampal areas, and prepiriform cortex. On the basis of afferent connections, it is possible to divide the cat's medial prefrontal cortex into an infralimbic component, MPFil, marked by strong afferents from prepiriform cortex and the cortical amygdala, and a dorsal component, MPFd, without afferents from these structures. Further, within MPFd, it is possible to define an axis, running from ventral and posterior to dorsal and anterior levels, along which limbic afferents gradually become weaker and projections from cortical association areas gradually become stronger.     

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.     

Afferent fibers to rat cingulate cortex

Afferent fibers to the rat cingulate cortex were studied by the retrograde labeling technique using horseradish peroxidase-wheat germ agglutinin conjugate as the tracer. The results showed that the posterior cingulate cortex, but not the anterior, received input from the anterior dorsal and anterior ventral nuclei of the anterior thalamic group of nuclei (part of the so-called limbic thalamus), and from the subicular complex. The anterior cingulate cortex, but not the posterior, received input from the mediodorsal and ventral thalamic nuclei. Both posterior and anterior cingulate cortex received input from the hippocampus pars anterior; claustrum; globus pallidus; nucleus of the diagonal band of Broca (a particularly reliable source of afferent fibers); anterior medial, lateral, rhomboid, and reuniens nuclei of the thalamus; region of the medial forebrain bundle; periventricular nucleus of the hypothalamus; the dorsal and median raphe; and the locus ceruleus. Corticocortical projections were seen anterior, posterior, and lateral to the injection site, and in the homologous contralateral cingulate cortex. The results demonstrate a prominent source of cingulate afferent fibers from the subicular complex, provide evidence for a functional division of anterior and posterior cingulate cortices in the rat, and provide information about the relative anatomic importance of cingulate afferent fibers from those different regions.     

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.     

An experimental study of the ventral striatum of the golden hamster. I. Neuronal connections of the nucleus accumbens

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the nucleus accumbens. Following iontophoretic applications or hydraulic injections of HRP in nucleus accumbens, cells labeled by retrograde transport of HRP were observed in the ipsilateral telencephalon in the posterior agranular insular, perirhinal, entorhinal, and primary olfactory cortices, in the subiculum and hippocampal field CA1, and in the anterior and posterior divisions of the basolateral amygdaloid nucleus. In the diencephalon, labeled neurons were present ipsilaterally in the central medial, paracentral and parafascicular intralaminar nuclei, and in the midline nuclei parataenialis, paraventricularis, and reuniens. Retrograde labeling was observed in the ipsilateral brainstem in cells of the ventral tegmental area and dorsal raphe. Many of these projections to nucleus accumbens were found to be topographically organized. Anterograde transport of HRP from nucleus accumbens demonstrated ipsilateral terminal fields in the ventral pallidum and substantia nigra, pars reticulata. The afferent projections to nucleus accumbens from the posterior insular and perirhinal neocortices, intralaminar thalamus, and the dopamine-containing ventral tegmental area are analogous to the connections of the caudatoputamen, as are the efferents from nucleus accumbens to the substantia nigra and ventral globus pallidus. These connections substantiate the classification of nucleus accumbens as a striatal structure and provide support for the recently proposed concept of the ventral striatum. Furthermore, the demonstration that a number of limbic system structures, including the amygdala, hippocampal formation, entorhinal cortex, and olfactory cortex are important sources of afferents to the nucleus accumbens, suggests that the ventral striatum may serve to integrate limbic information into the striatal system.     

Thalamic connections with limbic cortex. II. Corticothalamic projections

The corticothalamic projections from the cat limbic cortex have been investigated with anterograde and retrograde axonal transport techniques. Five limbic cortical areas—the anterior limbic area, the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum—were identified on the basis of their cytoarchitecture. Emphasis was placed on determining the laminar distribution of the cells of origin of the efferent projections, the projection pathways, and the sites of termination within the thalamus. Projections to the thalamus originate in layers V and VI of limbic cortex. In the cingular region the cells of origin are predominantly in layer V and to a lesser extent in layer VI, while the majority of cells projecting from the more caudal retrosplenial areas and presubiculum are in layer VI. There are two fiber pathways from each cortical area to the thalamus. One system of fibers passes through the internal capsule and lateral thalamic peduncle, and a second system travels in the cingulate fasciculus before piercing the corpus callosum to join the postcommissural fornix. The lateral dorsal nucleus and the anterior nuclear group, including the anterior dorsal, anterior ventral, and anterior medial nuclei, are the major thalamic recipients of projections from limbic cortex. Corticothalamic projections also terminate sparsely in the midline and intralaminar nuclear complex, including the central lateral, central dorsal, paracentral, central medial, rhomboid, and reuniens nuclei. Projections from the anterior limbic area project predominantly to the anterior medial, centrall lateral, and paracentral nuclei. The anterior ventral nucleus, anterior medial nucleus, and lateral dorsal nucleus are the major thalamic recipients of projections from the cingular area, the granular and dysgranular retro-splenial areas, and the presubiculum. It appears that the anterior dorsal nucleus receives afferents only from the dysgranular retrosplenial area. Bilateral corticothalamic projections were found in the anterior medial, dorsal medial, central lateral, central medial, paracentral, and reuniens nuclei.     

Afferent projections to the mammillary complex of the rat, with special reference to those from surrounding hypothalamic regions.

To better understand the functional organization of the mammillary nuclei, we investigated the afferents to this nuclear complex in the rat with iontophoretically injected wheat germ agglutinin conjugated to horseradish peroxidase. Particular attention was paid to tracing local hypothalamic afferents to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed strong projections from the subicular region, and weaker projections from the prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca. Other descending subcortical projections to the MMN arise from the anterior and the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of the stria terminalis. Ascending afferents to the MMN were found to originate in the raphe and various tegmental nuclei. Following all injections into the MMN, labelled neurons were found in nuclei surrounding the mammillary body. The lateral and posterior subdivisions of the tuberomammillary nucleus projected mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral premammillary nuclei projected to the pars lateralis of the MMN. The supramammillary nucleus at rostral level had a small projection to the pars medialis and lateralis of the MMN. However, the most obvious projection from this nucleus was to the pars posterior of the MMN, chiefly from the lateral part of the caudal supramammillary nucleus. Injections into the lateral mammillary nucleus revealed inputs from the presubiculum, parasubiculum, septal region, dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In addition, the lateral mammillary nucleus was found to receive a moderate projection from the medial part of the supramammillary nucleus and stronger projections from the lateral part of the caudal supramammillary nucleus. A very light projection was also seen from the lateral and posterior subdivisions of the tuberomammillary nucleus. These findings add to our knowledge of the extensive and complex connectivity of the mammillary nuclei. In particular, the local connections we have demonstrated with the supramammillary and tuberomammillary nuclei indicate the existence of significant local circuits as well as circuits involving more distant brain regions such as the septal nuclei, subiculum, prefrontal cortex, and brain stem tegmentum.     

Ascending projections of the posterior nucleus of the hypothalamus: PHA-L analysis in the rat

With the exception of a report by R. B. Veazey, D. G. Amaral, and W. M. Cowan (1982, J. Comp. Neurol. 207:135–156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris -leucoagglutinin (PHA-L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of atria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices. The diversity of PH projections to subcortical and cortical “limbic-related” sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events. © 1995 Wiley-Liss, Inc.     

Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat

The projections from the parabrachial nucleus to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-beta (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus (the lateral parafascicular, medial parafascicular, oval paracentral, central lateral, paracentral, and central medial nuclei), as well as the midline thalamic nuclei (the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, parvicellular part of the ventral posterior, and caudal ventral medial nuclei). The retrograde cell body labeling pattern within the parabrachial subnuclei was then analyzed. The paracentral thalamic nucleus received an input only from the internal lateral parabrachial subnucleus. However, this subnucleus also projected to all the other intralaminar thalamic nuclei, except for the central lateral thalamic nucleus, which received no parabrachial afferent inputs. The external lateral parabrachial subnucleus projected to the lateral parafascicular, reuniens, central medial, parvicellular part of the ventral posterior, and caudal ventromedial thalamic nuclei. Following CTb injections in the paraventricular thalamic nucleus, retrogradely labeled cells were found in the central lateral, dorsal lateral, and external lateral parabrachial subnuclei. The medial and ventral lateral parabrachial subnuclei projected to the oval paracentral, parafascicular, and rhomboid thalamic nuclei. Finally, the waist area of the parabrachial nucleus was densely labeled after CTb injections in the parvicellular part of the ventral posterior thalamic nucleus. Nociceptive, visceral, and gustatory signals may reach specific cortical and other forebrain sites via this parabrachial-thalamic pathway.     

Projections from the five divisions of the orbital cortex to the thalamus in the rat

The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we describe the efferent projections from the five divisions of the ORB to the thalamus in the rat. We demonstrated that, with some overlap, each division of the ORB distributed in a distinct (and unique) manner to nuclei of the thalamus. Overall, ORB projected to a relatively restricted number of sites in the thalamus, and strikingly distributed entirely to structures of the medial/midline thalamus, while completely avoiding lateral regions or principal nuclei of the thalamus. The main termination sites in the thalamus were the paratenial nucleus (PT) and nucleus reuniens (RE) of the midline thalamus, the medial (MDm) and central (MDc) divisions of the mediodorsal nucleus, the intermediodorsal nucleus, the central lateral, paracentral, and central medial nuclei of the rostral intralaminar complex and the submedial nucleus (SM). With some exceptions, medial divisions of the ORB (MO, VO) mainly targeted “limbic-associated” nuclei such as PT, RE, and MDm, whereas lateral division (VLO, LO, DLO) primarily distributed to “sensorimotor-associated” nuclei including MDc, SM, and the rostral intralaminar complex. As discussed herein, the medial/midline thalamus may represent an important link (or bridge) between the orbital cortex and the hippocampus and between the ORB and medial prefrontal cortex. In summary, the present results demonstrate that each division of the orbital cortex projects in a distinct manner to nuclei of the thalamus which suggests unique functions for each division of the orbital cortex.     

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.     

Afferent connections of the perirhinal cortex in the rat

Connections of the perirhinal cortex in the.rat brain were studied using anterograde (³H-proline/leucine) and retrograde (horseradish peroxidase) tracers. The perirhinal cortex receives major projections from medial precen-tral, anterior cingulate, prelimbic, ventral lateral orbital, ventral and posterior agranular insular, temporal, superior and granular parietal, lateral occipital, agranular retrosplenial, and ectorhinal cortices, and from the pre-subiculum, subiculum, and diagonal band of Broca. Rostral neocortical areas project predominantly to rostral perirhinal regions while more caudal neocortical and subicular areas project predominantly to caudal perirhinal regions. Terminal fields are further segregated within perirhinal cortex to either the dorsal or ventral banks of the rhinal sulcus. All afferents from frontal areas terminate predominantly in the deep layers of its ventral bank; afferents from temporal, parietal, and lateral occipital areas terminate predominantly in the deep and superficial layers along its dorsal bank; and afferents from ectorhinal cortex terminate in a column within its dorsal bank. Cortical cells which project to perirhinal areas are found predominantly in layer II and the superficial part of layer III. However, ventrolateral orbital, parietal, and lateral occipital cortex projections originate predominantly from layer V. Perirhinal areas also receive afferents from the nucleus reuniens of the thalamus, lateral nucleus of the amygdala, claustrum, supramammillary nuclei, and the dorsal raphe nuclei.     

Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum

The retrograde and anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) has been used to trace afferent connections of the rat mamillary body (MB) at the light and electron microscopic levels. Injections of WGA-HRP into different parts of the MB resulted in heavy retrograde labeling in the subicular complex, medial prefrontal cortex, and dorsal and ventral tegmental nuclei. Injections of WGA-HRP into each of these brain regions, respectively, resulted in anterograde labeling with specific distributions and characteristic synaptic organizations in the MB. Projections from the rostrodorsal and caudoventral subiculum terminated in a topographically organized laminar fashion in the medial mamillary nucleus bilaterally, whereas afferent projections from the presubiculum and parasubiculum terminated only in the lateral mamillary nucleus. Labeled axon terminals which originated from the subicular complex were characterized by round vesicles and formed asymmetric synaptic junctions with small-diameter dendrites and dendritic spines in the medial and lateral mamillary nuclei. Projections from the prefrontal cortex originated mainly in the infralimbic area and to a lesser degree in the prelimbic and anterior cingulate areas. Injections of tracer into these brain regions gave rise to dense labeling of axon terminals in the medial mamillary nucleus, pars medianus, and in the anterior dorsomedial portion of the pars medialis. The labeled terminals were characterized by round vesicles and formed asymmetric synaptic junctions with small-diameter dendrites and dendritic spines. Projections from the dorsal tegmental nucleus terminated in the ipsilateral lateral mamillary nucleus, whereas afferent projections from the anterior and posterior subnuclei of the ventral tegmental nucleus terminated topographically in the medial mamillary nucleus. The ventral tegmental nucleus, pars anterior projected to the midline region of the medial nucleus and the dorsolateral and ventromedial subdivisions of the pars posterior projected to medial and lateral parts of the medial nucleus, respectively. In contrast to the synaptic morphology of subicular complex and medial prefrontal cortex axon terminals in the MB, labeled axon terminals in the MB which originated from the midbrain tegmentum were characterized by pleomorphic vesicles and formed symmetric synaptic junctions with neuronal somata and proximal dendrites as well as distal dendrites and dendritic spines.(ABSTRACT TRUNCATED AT 400 WORDS)     

Excitatory actions of the ventral midline thalamus (rhomboid/reuniens) on the medial prefrontal cortex in the rat

The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. The present report examined the effects of stimulation of the midline thalamus, concentrating on ventral nuclei of the midline thalamus, on evoked activity at the mPFC. The nucleus reuniens (RE) of the ventral midline thalamus is a major source of projections to the hippocampus and to the mPFC, and has been shown to exert pronounced excitatory effects on the hippocampus. No previous study has systematically examined the actions of the ventral midline thalamus on the mPFC. We showed that stimulation of the dorsal and ventral midline thalamus, but not of an intermediate region lying between them (null zone), produced short latency, large amplitude evoked potentials throughout the dorsoventral extent of the medial PFC. The largest effects were elicited with ventral midline stimulation (rhomboid/reuniens nuclei) at the ventral mPFC--the prelimbic (PL) and infralimbic (IL) cortices. Specifically, stimulation of RE produced evoked potentials (early negative component, N2) at the PL cortex at a mean latency of 22.6 msec and mean amplitude of 0.85 mV, indicative of monosynaptic effects. In addition, we showed that paired pulse stimulation of RH/RE produced strong facilitatory actions (paired pulse facilitation) at IL (83%) and PL (75%). These findings indicate that RE exerts strong direct excitatory effects on the mPFC, and coupled with the demonstration that RE produces similar actions on the hippocampus, indicates that RE is in a position to influence and possibly coordinate the activity of these two forebrain structures subserving memory.     

An autoradiographic study of the efferent connections of the superior colliculus in the cat

The differential projections of the three main cellular strata of the superior colliculus have been examined in the cat by the autoradiographic method. The stratum griseum superficiale projects caudally to the parabigeminal nucleus and rostrally to several known visual centers: the nucleus of the optic tract and the olivary pretectal nucleus in the pretectum; the deepest C laminae of the dorsal lateral geniculate nucleus; the large-celled part of the ventral lateral geniculate nucleus; the posteromedial, large-celled part of the lateral posterior nucleus of the thalamus. Several of these projections are topographically organized. The stratum griseum profundum gives rise to most of the descending projections of the superior colliculus. Ipsilateral projections pass to both the dorsolateral and lateral divisions of the pontine nuclei, the cuneiform nucleus, and the raphe nuclei, and to extensive parts of the brainstem reticular formation: the tegmental reticular nucleus, and the paralemniscal, lateral, magnocellular, and gigantocellular tegmental fields. Contralateral projections descending in the predorsal bundle pass to the medial parts of the tegmental reticular nucleus and of some of the tegmental fields, the dorsal part of the medial accessory nucleus of the inferior olivary complex, and to the ventral horn of the cervical spinal cord. Ascending projections of the stratum griseum profundum terminate in several nuclei of the pretectum, the magnocellular nucleus of the medial geniculate complex and several intralaminar nuclei of the thalamus, and in the fields of Forel and zona incerta in the subthalamus. The strata grisea profundum and intermediale each have projections to homotopic areas of the contralateral superior colliculus, to the pretectum, and to the central lateral and suprageniculate nuclei of the thalamus. However, the stratum griseum intermediale has few or no descending projections.