Cortical projection patterns of the medial septum-diagonal band complex

A detailed analysis of the cortical projections of the medial septum-diagonal band (MS/DB) complex was carried out by means of anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial septum (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MS/DB complex, revealing a topographic organization of the MS/DB-cortical projection. In brief, the lateral and intermediate aspects of the HDB, also referred to as the magnocellular preoptic area, predominantly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDB and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and to a lesser degree at the medial mesolimbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects to the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion of the entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lateral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i.e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both "boutons en passant" and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here, the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers.     

Projections from the amygdaloid complex to the piriform cortex: A PHA-L study in the rat

Projections from the amygdala to the piriform cortex are proposed to provide a pathway via which the emotional system can modulate the processing of olfactory information as well as mediate the spread of seizure activity in epilepsy. To understand the details of the distribution and topography of these projections, we injected the anterograde tracer Phaseolus vulgaris-leucoagglutinin into different nuclear divisions of the amygdaloid complex in 101 rats and analyzed the distribution and density of projections in immunohistochemically processed preparations. The heaviest projections from the amygdala to the piriform cortex originated in the medial division of the lateral nucleus, the periamygdaloid and sulcal subfields of the periamygdaloid cortex, and the posterior cortical nucleus. The heaviest terminal labeling was observed in layers Ib and III of the medial aspect of the posterior piriform cortex. Lighter projections to the posterior piriform cortex originated in the dorsolateral division of the lateral nucleus, the magnocellular and parvicellular divisions of the basal and accessory basal nuclei, and the anterior cortical nucleus. The projections to the anterior piriform cortex were light and originated in the dorsolateral and medial divisions of the lateral nucleus, the magnocellular division of the basal and accessory basal nuclei, the anterior and posterior cortical nuclei, and the periamygdaloid subfield of the periamygdaloid cortex. The results indicate that only selective amygdaloid nuclei or their subdivisions project to the piriform cortex. In addition, substantial projections from several amygdaloid nuclei converge in the medial aspect of the posterior piriform cortex. Via these projections, the amygdaloid complex can modulate the processing of olfactory information in the piriform cortex. In pathologic conditions such as epilepsy, these connections might provide pathways for the spread of seizure activity from the amygdala to extra-amygdaloid regions.     

Prefrontal cortical projections to the cholinergic neurons in the basal forebrain

The prefrontal cortex (PFC) projections to the basal forebrain cholinergic cell groups in the medial septum (MS), vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and the magnocellular basal nucleus (MBN) in the rat were investigated by anterograde transport of Phaseolus vulgaris leuco-agglutinin (PHA-L) combined with acetylcholinesterase (AChE) histochemistry or choline acetyltransferase (ChAT) immunocytochemistry. The experiments revealed rich PHA-L-labeled projections to discrete parts of the basal forebrain cholinergic system (BFChS) essentially originating from all prefrontal areas investigated. The PFC afferents to the BFChS display a topographic organization, such that medial prefrontal areas project to the MS, VDB, and the medial part of the HDB, whereas the orbital and agranular insular areas predominantly innervate the HDB and MBN, respectively. Since the recurrent BFChS projection to the prefrontal cortex is arranged according to a similar topography, the relationship between the BFChS and the prefrontal cortex is characterized by reciprocal connections. Furthermore, tracer injections in the PFC resulted in anterograde labeling of numerous "en passant" and terminal boutons apposing perikarya and proximal dendrites of neurons in the basal forebrain, which were stained for the cholinergic marker enzymes. These results indicate that prefrontal cortical afferents make direct synaptic contacts upon the cholinergic neurons in the basal forebrain, although further analysis at the electron microscopic level will be needed to provide conclusive evidence.     

Thalamic projections to the posteromedial cortex in the macaque

The medial parietal, posterior cingulate, and retrosplenial cortices collectively constitute a region of cortex referred to as the posteromedial cortices (PMC). In an effort to shed light on the neuroanatomical organization of the PMC, we undertook a study to identify and analyze the thalamocortical connections of these cortices. Retrograde tracer injections were placed in the posterior cingulate (PCC), retrosplenial (RSC), medial parietal cortices (MPC), and posterior cingulate sulcus (PCS), and the labeling patterns within the thalamus were analyzed. Three afferent projection patterns were observed to the PMC from the thalamus: a PCC/RSC pattern that involved the anterior thalamic nuclei, an MPC pattern that involved the lateral posterior and pulvinar nuclei, and a PCS pattern that involved the ventral thalamic nuclei. Additionally, a shared pattern of projections from the anterior intralaminar nuclei (AILN) and posterior thalamic nuclei (PTN) to all cortical regions of the PMC was observed. Our findings suggest that distinct regions within the PMC are supplied by distinctive patterns of thalamic input, but also share common projections from intralaminar and posterior thalamic sources. In addition, we relate our findings to functional abnormalities in aging and dementia, and address a domain-like pattern of thalamocortical labeling of the PMC that is drawn selectively and collectively from multiple thalamic nuclei.     

Association and commissural fiber systems of the olfactory cortex of the rat. I. Systems originating in the piriform cortex and adjacent areas

The association and commissural fiber systems arising in the olfactory cortical areas caudal to the olfactory peduncle (the piriform cortex, nucleus of the lateral olfactory tract, anterior cortical nucleus of the amygdala, periamygdaloid cortex and entorhinal cortex) have been studied utilizing horseradish peroxidase as both an anterograde and a retrograde axonal tracer. In the piriform cortex two sublaminae within layer II (IIa and IIb) and layer III have been found to give rise to distinctly different projections. Retrograde cell labeling experiments indicate that the association fiber projection from layer IIb is predominantly caudally directed, while the projection from layer III is predominantly rostrally directed. Cells in layer IIa project heavily to areas both caudal and rostral to the piriform cortex. The commissural fibers from the piriform cortex are largely restricted in their origin to layer IIb of the anterior part of the piriform cortex and in their termination on the contralateral side to the posterior part of the piriform cortex and adjacent olfactory cortical areas. A projection to the olfactory bulb has also been found to arise from cells in layers IIb and III of the ipsilateral piriform cortex, but not in layer IIa. In addition to those from the piriform cortex, association projections have also been found from other olfactory cortical areas. The nucleus of the lateral olfactory tract has a heavy bilateral projection to the medial part of the anterior piriform cortex and the lateral part of the olfactory tubercle (as well as a lighter projection to the olfactory bulb); both the anterior cortical nucleus of the amygdala and the periamygdaloid cortex project ipsilaterally to several olfactory cortical areas. The entorhinal cortex has been found to project to the medial parts of the olfactory tubercle and the olfactory peduncle. The olfactory tubercle is the only olfactory cortical area from which no association fiber systems (instrinsic or extrinsic) have been found to originate. A broad topographic organization exists in the distribution of the fibers from several of the olfactory areas. This is most obvious in the anterior part of the olfactory cortex, in which fibers from the more rostral areas (the anterior olfactory nucleus and the anterior piriform cortex) terminate in regions near the lateral olfactory tract, while those from more caudal areas (the posterior piriform cortex and the entorhinal cortex) terminate in areas further removed, both laterally and medially, from the tract. Projections to olfactory areas from the hypothalamus, thalamus, diagonal band, and biogenic amine cell groups have been briefly described.     

the connections of the mouse olfactory bulb: A study using orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

The efferent and centrifugal afferent connections of the main olfactory bulb (MOB) of the mouse were studied by orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). MOB projects ipsilaterally to the anterior olfactory nucleus, taenia tecta, anterior hippocampal continuation, indusium grisium, olfactory tubercle, and the lateral and medial divisions of the entorhinal area. In the region of the anterior one-half to two-thirds of the posterior division of the insular cortex the projection from MOB extends into the insular cortex. The only efferent projection of MOB to the contralateral half of the brain was to the anterior olfactory nucleus. All efferent projections of MOB, thus, are to telencephalic structures. By contrast the centrifugal afferents to MOB originate from every major division of the neuraxis. Neurons projecting to the bulb were found ipsilaterally in all divisions of the anterior olfactory nucleus (AON). In some cases, labeling in the external division of AON was weak or absent. In the contralateral AON, pars externa was the most intensively labeled sub-division. Retrogradely labeled neurons were also present in all other subdivisions of the contralateral AON but were fewer in number and less heavily labeled than in the ipsilateral AON. Ipsilaterally, positive neurons were also present in taenia tecta, and the anterior hippocampal continuation. There was profuse retrograde labeling of neurons in the entire extent of the ipsilateral piriform cortex (PC). There was a rostral to caudal gradient of labeling in PC with more positive neurons in rostral than caudal parts. Labeled neurons were present in the lateral entorhinal cortex LEC and in the transitional cortex between LEC and PC. Very heavy retrograde labeling was present in the nuclei of the horizontal and vertical limbs of the diagonal band (HDB and VDB). More cells were labeled in HDB than in VDB. Neurons were labeled in the ipsilateral nucleus of the lateral olfactory tract (NLOT) and, when the injection spread into the accessory olfactory bulb, labeled neurons were present ventral to NLOT in accessory NLOT. A few lightly labeled neurons were always present in the posterolateral and medial cortical amygdaloid areas. Neurons were labeled in the zona inserta and scattered throughout several hypothalamic nuclei. There was massive retrograde labeling of neurons in the locus coeruleus and neurons were abundantly labeled in the dorsal and medial raphe nuclei and nucleus raphe pontis. In general, the labeling of MOB connections was more extensive than that which has been reported in closely related species.(ABSTRACT TRUNCATED AT 400 WORDS)     

Organization of ascending hypothalamic projections to the rostral forebrain with special reference to the innervation of cholinergic projection neurons

Axonal projections from hypothalamic nuclei to the basal forebrain, and their relation to cholinergic projection neurons in particular, were studied in the rat by using the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in combination with choline acetyltransferase (ChAT) immunocytochemistry. Discrete iontophoretic PHA-L injections were delivered to different portions of the caudal lateral hypothalamus, as well as to various medial hypothalamic areas, including the ventromedial, dorsomedial, and paraventricular nuclei, and anterior hypothalamic and medial preoptic areas. The simultaneous detection of PHA-L-labeled fibers/terminals and ChAT-positive neurons was performed by using nickel-enhanced diaminobenzidine (DAB) and nonenhanced DAB as chromogens. Selected cases were investigated at the electron microscopic level. Ascending hypothalamic projections maintained an orderly lateromedial arrangement within the different components of the medial forebrain bundle, as well as with respect to their terminal projection fields (e.g., within the bed nucleus of the stria terminalis and lateral septal nucleus). The distribution pattern of hypothalamic inputs to cholinergic projection neurons corresponded to the topography of ascending hypothalamic axons. Axons originating from neurons in the far-lateral hypothalamus reached cholinergic neurons in a zone that extended from the dorsal part of the sublenticular substantia innominata (SI) caudolaterally, to the lateral portion of the bed nucleus of the stria terminalis rostromedially, encompassing a narrow band along the ventral part of the globus pallidus and medial portion of the internal capsule. Axons originating from cells in the medial portion of the lateral hypothalamus reached cholinergic cells primarily in more medial and ventral parts of the SI, and in the magnocellular preoptic nucleus and horizontal limb of the diagonal band nucleus (HDB). Axons from medial hypothalamic cells appeared to contact cholinergic neurons primarily in the medial part of the HDB, and in the medial septum/vertical limb of the diagonal band complex. Electron microscopic double-labeling experiments confirmed contacts between labeled terminals and cholinergic cells in the HDB and SI. Individual hypothalamic axons established synapses with both cholinergic and noncholinergic neuronal elements in the same regions. These findings have important implications for our understanding of the organization of afferents to the basal forebrain cholinergic projection system.     

Contralateral projections of the rat anterior olfactory nucleus

The anterior olfactory nucleus (AON) is a central olfactory cortical structure that has heavy reciprocal connections with both the olfactory bulb (OB) and piriform cortex. While it has been firmly established that the AON is a primary source of bilateral projections in the olfactory system through extensive connections with both the ipsilateral and contralateral OB, AON, and piriform cortex, few studies have examined this circuitry in detail. In the present study we used small injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde tracer FluoroGold in specific subregions of the AON to explore the topography of the interconnections between the left and right AONs. Labeled fibers were found in the contralateral AON following injections in all areas. However, detailed quantitative analyses revealed that different regions of the AON have distinct patterns of interhemispheric innervation; contralateral fibers were most heavily targeted to dorsal and lateral AON subregions, while the medial and ventral areas received relatively light projections. These results demonstrate important features of the interhemispheric circuitry of the AON and suggest separate functional roles for subregions of the AON in olfactory information processing.     

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.     

Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study

The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.     

Organization of projections from the basomedial nucleus of the amygdala: A PHAL study in the rat

The organization of axonal projections from the basomedial nucleus of the amygdala (BMA) was examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The anterior and posterior parts of the BMA, recognized on cytoarchitectonic grounds, display very different projection patterns. Within the amygdala, the anterior basomedial nucleus (BMAa) heavily innervates the central, medial, and anterior cortical nuclei. In contrast, the posterior basomedial nucleus (BMAp) sends a dense projection to the lateral nucleus, and to restricted parts of the central and medial nuclei. Extra-amygdalar projections from the BMA are divided into ascending and descending components. The former end in the cerebral cortex, striatum, and septum. The BMAa mainly innervates olfactory (piriform, transitional) and insular areas, whereas the BMAp also innervates inferior temporal (perirhinal, ectorhinal) and medial prefrontal (infralimbic, prelimbic) areas and the hippocampal formation. Within the striatum, the BMAa densely innervates the striatal fundus, whereas the nucleus accumbens receives a heavy input from the BMAp. Both parts of the BMA send massive projections to distinct regions of the bed nuclei of the stria terminalis. Descending projections from the BMA end primarily in the hypothalamus. The BMAa sends a major input to the lateral hypothalamic area, whereas the BMAp innervates the ventromedial nucleus particularly heavily. Injections were also placed in the anterior cortical nucleus (COAa), a cell group superficially adjacent to the BMAa. PHAL-labeled axons from this cell group mainly ascend into the amygdala and olfactory areas, and descend into the thalamus and lateral hypothalamic area. Based on connections, the COAa and BMAa are part of the same functional system. The results suggest that cytoarchitectonically distinct anterior and posterior parts of the BMA are also hodologically distinct and form parts of distinct anatomical circuits probably involved in mediating different behaviors (for example, feeding and social behaviors vs. emotion-related learning, respectively). © 1996 Wiley-Liss, Inc.     

Differential projections of the main and accessory olfactory bulb in the frog.

The central projections of the main olfactory bulb and the accessory olfactory bulb of the adult leopard frog (Rana pipiens) were reexamined, by using a horseradish peroxidase anterograde tracing method that fills axons with a continuous deposit of reaction product. The fine morphology preserved by this method allowed the terminal fields of the projection tracts to be delineated reliably, and for the first time. Herrick's amygdala has been newly subdivided into cortical and medial nuclei on the basis of cytoarchitecture, dendritic morphology, and the differential projections of the main and accessory olfactory tracts. The main olfactory bulb projects through the medial and lateral olfactory tracts to the postolfactory eminence, the rostral end of the medial cortex, the rostral end of the medial septal nucleus, the cortical amygdaloid nucleus, the nucleus of the hemispheric sulcus, and both the dorsal and ventral divisions of the lateral cortex, including its retrobulbar fringe. The lateral olfactory tract overlaps the dorsal edge of the striatal plate along the ventral border of the lateral cortex, but it is not certain whether any striatal cells are postsynaptic to the tract fibers. The lateral cortex is the largest of these territories, and receives the terminals of the main olfactory projection throughout its extent. It extends from the olfactory bulb to the posterior pole, and from the striatum to the summit of the hemisphere, where it borders the dorsal cortex. The medial and lateral olfactory tracts combine in the region of the amygdala to form a part of the stria medullaris thalami. These fibers cross in the habenular commissure and terminate in the contralateral cortical amygdaloid nucleus and periamygdaloid part of the lateral cortex. Cells projecting to the main olfactory bulb are found in the diagonal band and adjacent cell groups, but there is no evidence of an interbulbar projection arising from either the olfactory bulb proper or a putative anterior olfactory nucleus. The accessory olfactory bulb projects through the accessory olfactory tract to the medial and cortical amygdaloid nuclei. A fascicle of the tract crosses in the anterior commissure to terminate in the contralateral amygdala. While the main and accessory olfactory projections may converge in the cortical amygdaloid nucleus, the medial amygdaloid nucleus is connected exclusively with the accessory olfactory bulb.     

Retrograde labelling of mitral/tufted cells in the mouse accessory olfactory bulb following local injections of the lipophilic tracer DiI into the vomeronasal amygdala

It has recently become apparent that there are two classes of vomeronasal receptor neurons that project to functionally separate anterior and posterior sub-regions of the mammalian accessory olfactory bulb. However, anterograde tracing of the projections from these sub-regions, in the mouse, has revealed that the processing pathways are not segregated at the level of the vomeronasal amygdala. Both sub-regions have overlapping projections to the superficial lamina of the medial and posterior medial cortical nuclei of the amygdala. However, differential projections have been found in the opossum, in which only the posterior sub-region projects to the deeper laminae of the medial amygdala. Therefore, there may be species differences in these projections that are important for the control of reproductive behaviour. This study used an alternative approach of retrogradely tracing mitral/tufted cell projections from different nuclei of the vomeronasal amygdala back to the accessory olfactory bulb of mice. Local injections of the lipophilic tracer DiI were made into the antero-dorsal and postero-ventral divisions of the medial amygdala, and into the postero-medial cortical amygdala. In each case, provided the DiI affected the superficial lamina Ia, labelled mitral/tufted cells were found distributed throughout the anterior-posterior extent of the accessory olfactory bulb. These results confirm that mitral/tufted cells of the anterior and posterior sub-regions of the accessory olfactory bulb project to both the medial and postero-medial cortical nuclei of the amygdala. There was no evidence for differential projections from the anterior and posterior sub-regions accessory olfactory bulb in mice, as has been reported to occur in other species.     

Organization of the cerebellum in the pigeon (Columba livia): I. Corticonuclear and corticovestibular connections.

The projections of the cerebellar cortex upon the cerebellar nuclei and the vestibular complex of the pigeon have been delineated using WGA-HRP as an anterograde and retrograde tracer. Injections into individual cortical lobules (II-IXa) produce a pattern of ipsilateral terminal labeling of both the cerebellar and vestibular nuclei. The pattern of corticonuclear projections indicates both a rostrocaudal and a mediolateral organization with respect to the lobules and is consistent with a division of the cerebellar nuclei into a medial (CbM) and a lateral (CbL) nucleus. The retrograde experiments indicate that these nuclei receive projections, respectively, from Purkinje cells within medial (A) and lateral (C) longitudinal zones, which alternate with longitudinal zones (B, E) projecting upon the vestibular complex. Purkinje cells in (vestibulocerebellar) lobules IXb-X show only limited projections upon the cerebellar nuclei, but do project extensively upon the cerebellovestibular process (PCV), as well as upon the medial, superior, and descending vestibular nuclei. As the injection site shifts from medial to lateral, there is a corresponding shift in focus of the projection within PCV from areas bordering CbM to those abutting CbL. The topographic organization of corticovestibular projections is less clear-cut than those of the corticonuclear projections. Lobules II-X project upon the lateral vestibular nucleus (anterior lobe) or the dorsolateral vestibular nucleus (posterior lobe). These projections originate from either side of the lateral (C) zone. Projections originating from the medialmost (B) zone are interrupted in lobules VI and VII. The anterior and posterior portions of the lateralmost (E) zone overlap along lobules VI and VII. In addition, the E zone of the anterior lobe is the source of projections upon the medial, the descending, and the superior vestibular nuclei. Projections from the auricle and adjacent lateral unfoliated cortex (F zone) focus upon the infracerebellar nucleus, the medial tangential nucleus, and the medial division of the superior vestibular nucleus. The data suggest that the cerebellar cortex of the pigeon, like that of mammals, may be subdivided into a mediolaterally oriented series of longitudinal zones, with Purkinje cells in each zone projecting ipsilaterally to specific cerebellar nuclei or vestibular regions. For cortical regions exclusive of the auricle and lateral unfoliated cortex, three such zones (A, B, and C) are defined that are comparable in their efferent targets with the A, B, and C zones of mammals. There does not appear to be a D zone in the pigeon. The results are discussed in relation to comparative data on amphibians, reptiles, and mammals.     

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.     

Cholinergic neurons of the laterodorsal tegmental nucleus: efferent and afferent connections

The ascending projections of cholinergic neurons in the laterodorsal tegmental nucleus (TLD) were investigated in the rat by using Phaseolus vulgaris leucoagglutinin (PHA-L) and wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) anterograde tracing techniques. Two ascending pathways were identified after iontophoretic injections of PHA-L into the TLD. A long projection system courses through the dorsomedial tegmentum, caudal diencephalon, medial forebrain bundle, and diagonal band. Different branches of this system innervate the midbrain (superior colliculus, interstitial magnocellular nucleus of the posterior commissure, and anterior pretectal nucleus), the diencephalon (lateral habenular nucleus, parafascicular, anteroventral, anterodorsal, mediodorsal, and intralaminar thalamic nuclei), and the telencephalon (lateral septum and medial prefrontal cortex). The second system is shorter and more diffuse and innervates the median raphe, interpeduncular, and lateral mammillary nuclei. Retrograde tracing with WGA-HRP, combined with choline acetyltransferase immunohistochemistry, revealed that most of the TLD projections to the tectum, pretectum, thalamus, lateral septum, and medial prefrontal cortex are cholinergic. Afferents to the TLD were studied by anterograde and retrograde tracing techniques. Injection of tracers into the TLD retrogradely labelled neurons bilaterally in the midbrain reticular formation, the periaqueductal gray, the medial preoptic nucleus, the anterior hypothalamic nucleus, and the perifornical and lateral hypothalamic areas. Retrogradely labelled cells were also located bilaterally in the premammillary nucleus, paraventricular hypothalamic nucleus, zona incerta, and lateral habenular nucleus. In the telencephalon, the nucleus of the diagonal band and the medial prefrontal cortex contained retrogradely labelled neurons ipsilateral to the TLD injection site. The projections of the medial prefrontal cortex, the bed nucleus of the stria terminalis, and the lateral habenular nucleus to the TLD were confirmed in anterograde tracing studies. These findings indicate that the TLD gives rise to several ascending cholinergic projections that innervate diverse regions of the forebrain. Afferents to the TLD arise in hypothalamic and limbic forebrain regions, some of which appear to have reciprocal connections with the TLD. The latter include the lateral habenular nucleus and medial prefrontal cortex.     

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.     

Efferents and centrifugal afferents of the main and accessory olfactory bulbs in the hamster

The efferents and centrifugal afferents of the hamster olfactory bulbs were studied using orthograde and retrograde tracing techniques. Following injections of tritiated amino acids which were restricted to the main olfactory bulb (MOB), autoradiographic grains were observed ipsilaterally over layer IA of the entire anterior olfactory nucleus (AON), the ventral portion of the hippocampal rudiment (HR), the entire prepyriform cortex and olfactory tubercle, the anterior and posterolateral cortical amygdaloid nuclei and the lateral entorhinal cortex. An ipsilateral projection to the nucleus of the lateral olfactory tract (nLOT) was also indicated. No subcortical or contralateral projections were observed. Amino acid injections into the accessory olfactory bulb (AOB) revealed ipsilateral projections to the superficial plexiform layer of the medial and posteromedial cortical amygdaloid nuclei and to the bed nucleus of the accessory olfactory tract (nAOT) and the bed nucleus of the stria terminalis (nST). Following injections of HRP which were restricted to the MOB, contralateral HRP-positive neurons were found predominantly in pars externa and to a lesser extent in the other subdivisions of the AON. Centrifugal projections to the MOB were identified ipsilaterally from the entire AON, the ventral portion of the HR, the anterior portion of the prepyriform cortex, and the nLOT. No labelled neurons were found in the olfactory tubercle, the anterior and posterolateral cortical amygdaloid nuclei or the entorhinal cortex. Centrifugal projections to the MOB were also identified from subcortical structures of the ipsilateral basal forebrain and from midline structures of the midbrain. Labelling occurred in the fusiform neurons of the diagonal band near the medial base of the forebrain at the level of caudal olfactory tubercle. Heavy labelling was seen in a distinct group of large, predominantly multipolar neurons (magnocellular preoptic area) that continued from the level of caudal olfactory tubercle to the level of the nLOT. This band of HRP-positive neurons could be followed more caudally to a position dorsal and medial to the nLOT near the lateral margin of the lateral anterior hypothalamic area. The midbrain projections to the MOB originated in the dorsal and median raphe nuclei. After injections of HRP into the AOB, centrifugal projections were identified from the nAOT and the posteromedial cortical amygdaloid nucleus. In addition, isolated neurons were labelled in the medial cortical amygdaloid nucleus but no labelled neurons were found in the nST. These results support the notion of two anatomically distinct olfactory systems and demonstrate two previously unreported pathways through which the limbic system may modulate sensory processing in the olfactory bulb.     

Efferent connections of the lateral cortex of the lizard gekko gecko: Evidence for separate origins of medial and lateral pathways from the lateral cortex to the hypothalamus

The lateral cortex of the lizard Gekko gecko is composed of three parts: a dorsal and ventral part located rostrally and a posterior part located caudally. In order to obtain detailed information about the efferent connections of these lateral cortex subdivisions, iontophoretic injections of the anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran were made in the various parts. The main projection from the dorsal part terminates in the caudal part of the medial cortex. Other cortical projections were noted to the ipsi- and contralateral lateral cortex, the large-celled part of the medial cortex, and the dorsal cortex. Additional fibers were found bilaterally in the anterior olfactory nucleus and the external amygdaloid nucleus. The ventral part of the lateral cortex projects mainly to the ipsilateral, posterior part of the dorsal ventricular ridge and the external amygdaloid nucleus. Minor contralateral projections to these nuclei were also found. Other projections were observed to travel to the caudal part of the medial cortex, to the nucleus sphericus, and bilaterally to the lateral cortex and the anterior olfactory nucleus. The posterior part of the lateral cortex has similar efferent connections as the dorsal part and should be regarded as the caudal continuation of the dorsal part. Because previous studies have shown that the medial cortex and the amygdaloid complex project to different hypothalamic areas, we conclude that the dorsal and ventral parts of the lateral cortex transmit olfactory information to separate hypothalamic areas that are probably involved with different types of behavior. © 1995 Wiley-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.