Cortical projections of the non-entorhinal hippocampal formation in the cynomolgus monkey (Macaca fascicularis)

Episodic memory consolidation requires the integrity of the anatomical pathways between the cerebral cortex and the hippocampal formation. Whilst the largest cortical output of the hippocampal formation originates in the entorhinal cortex, direct projections from CA1, subiculum and presubiculum to the cortex have been reported. The aim of this study is the assessment of the extent, topography and relative strength of those projections, as a parallel/alternate route of memory processing. A total of 45 injections in 28 Macaca fascicularis monkeys were used. Cortical deposits of fluorescent tracers (20 cases, 3% Fast Blue, 2% Diamidino Yellow) or 1% WGA-HRP (eight cases) were made in different cortical areas of the frontal, temporal and parietal lobes, as well as cingulate cortex by direct exposure of the cortical surface. After appropriate survival, animals were perfused and the brains serially sectioned at 50 microm and the retrograde labelling charted with an X-Y digitizing system. Retrograde neuronal labelling was observed in CA1, subiculum, presubiculum and parasubiculum; it was absent in the dentate gyrus, CA3 and CA2. Compared to other portions of the hippocampal formation, the CA1-subiculum border had the highest number of labelled neurons (especially after deposits in the rostral perirhinal cortex), followed by medial frontal cortex, temporal pole, orbitofrontal, anterior and posterior cingulate cortices, parietal and inferotemporal cortices, and no labelling after posterior inferotemporal and lateral frontal cortices. Our results indicate that CA1, subiculum, presubiculum and parasubiculum send direct output to cortical areas. This nonentorhinal, hippocampal formation cortical output may be relevant in memory processing.     

Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transportedPhaseolus vulgaris leucoagglutinin

The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). After immunocytochemical visualization of labeled efferents, the distribution of projections over the cortical mantle, olfactory regions and amygdala were studied by light microscopy. Based on differences in cortical projection patterns, the MBN was subdivided in anterior, intermediate and posterior portions (MBNa, MBNi and MBNp). All subdivisions maintain neocortical projections and are subject to an anterior to posterior topographic arrangement. In the overall pattern, however, the frontal cortex is the chief target. Furthermore, all MBN parts project to various regions of meso- and allocortex, which are progressively more dense when the tracer injection is more anteriorly placed. The most conspicuous finding, however, was a ventrolateral to dorsomedial cortical projection pattern as the PHA-L injection site moved from posterior to anterior. Thus, the posterior MBN projects predominantly to lateral neo- and mesocortex while the anterior MBN sends more fibers to the medial cortical regions. Furthermore, the MBNa is a source of considerable afferent input to the olfactory nuclei and as such should be regarded as a transition to the HDB. The HDB, apart from projecting densely to olfactory bulb and related nuclei, maintains a substantial output to the medial prefrontal cortical regions and entorhinal cortex, as well. Comparison of young vs aged cases indicate that aging does not appear to have a profound influence on cortical innervation patterns, at least as studied with the PHA-L method.     

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.     

Connections of the parahippocampal cortex in the cat. II. Subcortical afferents

The organization of subcortical inputs to the parahippocampal cortex, which in the present study in the cat is considered to comprise the entorhinal and perirhinal cortices, was studied by using retrograde and anterograde tracing techniques. The results of the retrograde tracer horseradish peroxidase (HRP), HRP conjugated with wheat germ agglutinine (WGA-HRP), Fast Blue (FB) or Nuclear Yellow (NY] injections indicate that the entorhinal and perirhinal cortices receive inputs from the magnocellular basal forebrain and from distinct portions of the amygdaloid complex, the claustrum, and the thalamus. The two cortices are further projected upon by fibers from the supramamillary region of the hypothalamus, the ventral tegmental area of the mesencephalon, the dorsal raphe nucleus, the nucleus centralis superior, and the locus coeruleus. The entorhinal cortex, in addition, receives projections from the medial septum. As regards the projections from the amygdaloid complex, it was observed that the entorhinal cortex receives its heaviest input from the basolateral amygdaloid nucleus, whereas the perirhinal cortex receives a strong projection from the lateral nucleus and a weaker projection from the basomedial nucleus of the amygdala. Of the thalamic nuclei that project to the parahippocampal cortex, the nucleus reuniens is only connected with the entorhinal cortex, while fibers from the medial geniculate nucleus and the lateral posterior nucleus terminate in the perirhinal cortex. Injections of tritiated amino acid (3H-leucine) were placed in the medial septum, the dorsal and ventral claustrum, the basolateral and basomedial amygdaloid nuclei, and the nucleus reuniens of the thalamus. The results of these experiments demonstrate that, with the exception of the claustrum, these subcortical areas project mainly to the superficial layers I-III and the lamina dissecans of the parahippocampal cortex, and to a lesser degree to the deep layers V and VI.     

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.     

Medial temporal lobe projections to the retrosplenial cortex of the macaque monkey

The projections to the retrosplenial cortex (areas 29 and 30) from the hippocampal formation, the entorhinal cortex, perirhinal cortex, and amygdala were examined in two species of macaque monkey by tracking the anterograde transport of amino acids. Hippocampal projections arose from the subiculum and presubiculum to terminate principally in area 29. Label was found in layer I and layer III(IV), the former seemingly reflecting both fibers of passage and termination. While the rostral subiculum mainly projects to the ventral retrosplenial cortex, mid and caudal levels of the subiculum have denser projections to both the caudal and dorsal retrosplenial cortex. Appreciable projections to dorsal area 30 [layer III(IV)] were only seen following an extensive injection involving both the caudal subiculum and presubiculum. This same case provided the only example of a light projection from the hippocampal formation to posterior cingulate area 23 (layer III). Anterograde label from the entorhinal cortex injections was typically concentrated in layer I of 29a–c, though the very caudal entorhinal cortex appeared to provide more widespread retrosplenial projections. In this study, neither the amygdala nor the perirhinal cortex were found to have appreciable projections to the retrosplenial cortex, although injections in either medial temporal region revealed efferent fibers that pass very close or even within this cortical area. Finally, light projections to area 30V, which is adjacent to the calcarine sulcus, were seen in those cases with rostral subiculum and entorhinal injections. The results reveal a particular affinity between the hippocampal formation and the retrosplenial cortex, and so distinguish areas 29 and 30 from area 23 within the posterior cingulate region. The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum. © 2012 Wiley Periodicals, Inc.     

Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior

Common efferent projections of the dorsolateral prefrontal cortex and posterior parietal cortex were examined in 3 rhesus monkeys by placing injections of tritiated amino acids and HRP in frontal and parietal cortices, respectively, of the same hemisphere. Terminal labeling originating from both frontal and parietal injection sites was found to be in apposition in 15 ipsilateral cortical areas: the supplementary motor cortex, the dorsal premotor cortex, the ventral premotor cortex, the anterior arcuate cortex (including the frontal eye fields), the orbitofrontal cortex, the anterior and posterior cingulate cortices, the frontoparietal operculum, the insular cortex, the medial parietal cortex, the superior temporal cortex, the parahippocampal gyrus, the presubiculum, the caudomedial lobule, and the medial prestriate cortex. Convergent terminal labeling was observed in the contralateral hemisphere as well, most prominently in the principal sulcal cortex, the superior arcuate cortex, and the superior temporal cortex. In certain common target areas, as for example the cingulate cortices, frontal and parietal efferents terminate in an array of interdigitating columns, an arrangement much like that observed for callosal and associational projections to the principal sulcus (Goldman-Rakic and Schwartz, 1982). In other areas, frontal and parietal terminals exhibit a laminar complementarity: in the depths of the superior temporal sulcus, prefrontal terminals are densely distributed within laminae I, III, and V, whereas parietal terminals occupy mainly laminae IV and VI directly below the prefrontal bands. Subcortical structures also receive apposing or overlapping projections from both prefrontal and parietal cortices. The dorsolateral prefrontal and posterior parietal cortices project to adjacent, longitudinal domains of the neostriatum, as has been described previously (Selemon and Goldman-Rakic, 1985); these projections are also found in close apposition in the claustrum, the amygdala, the caudomedial lobule, and throughout the anterior medial, medial dorsal, lateral dorsal, and medial pulvinar nuclei of the thalamus. In the brain stem, both areas of association cortex project to the intermediate layers of the superior colliculus and to the midline reticular formation of the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cortical topography of thalamic intralaminar nuclei

The coritical projection of the thalamic intralaminar nuclei (ILN) has been studied by injecting little amounts of horseradish peroxidase (HRP) on the cerebral cortex of the rat. All of the cortical areas (except area 17) receive ipsilateral projections from at least one nucleus of the ILN. The nucleus centralis had the largest number of labeled neurons, principally after injections in frontal, temporal and occipital cortical areas. The nucleus paracentralis presented only moderate numbers of HRP positive neuronrs from the frontal cortex, and very few from parietal and temporal areas. The nucleus parafascicularis showed labeled somata after frontal injections as well as parietal and temporal areas. In comparison to the other ILN, the amount of labeled neurons in this nucleus is relatively small. The nucleus centralis medialis presented the least number of labeled neurons regardless of injected area. Its cortical efferents remain restricted to small areas of the dorsal aspects of frontal, anterior cingular and temporal cortices. Each of the ILN contains neurons which connect with more than one cortical zone, according to a characteristics topographic distribution.     

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long‐term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. J. Comp. Neurol. 523:2570–2598, 2015. © 2015 Wiley Periodicals, Inc.     

Cortical efferents of the perirhinal,postrhinal, and entorhinal cortices of the rat

We investigated the cortical efferents of the parahippocampal region by placing injections of the anterograde tracers, Phaseolus vulgaris‐leuccoagglutinin, and biotinylated dextran amine, throughout the perirhinal (PER), postrhinal (POR), and entorhinal cortices of the rat brain. The resulting density of labeled fibers was evaluated in 25 subregions of the piriform, frontal, insular, temporal, cingulate, parietal, and occipital areas. The locations of labeled terminal fibers differed substantially depending on whether the location of the injection site was in PER area 35, PER area 36, POR, or the lateral or the medial entorhinal (LEA and MEA). The differences were greater for sensory regions. For example, the POR efferents preferentially target visual and spatial regions, whereas the PER efferents target all sensory modalities. The cortical efferents of each region largely reciprocate the cortical afferents, though the degree of reciprocity varied across originating and target regions. The laminar pattern of terminal fibers was consistent with the notion that the efferents are feedback projections. The density and amount of labeled fibers also differed substantially depending on the regional location of injection sites. PER area 36 and POR give rise to a greater number of heavy projections, followed by PER area 35. LEA also gives rise to widespread cortical efferents, arising mainly from a narrow band of cortex adjacent to the PER. In contrast, the remainder of the LEA and the MEA provides only weak efferents to cortical regions. Prior work has shown that nonspatial and spatial information is transmitted to the hippocampus via the PER‐LEA and POR‐MEA pathways, respectively. Our findings suggest that the return projections follow the same pathways, though perhaps with less segregration. © 2009 Wiley‐Liss, Inc.     

Heterotopic Cortical Afferents to the Medial Prefrontal Cortex in the Rat. A Combined Retrograde and Anterograde Tracer Study

Cortical afferent projections towards the medial prefrontal cortex (mPFC) were investigated with retrograde and anterograde tracer techniques. Heterotopical afferent projections to the medial prefrontal cortex arise in secondary, or higher order, sensory areas, motor areas and paralimbic cortices. On the basis of these projections three subfields can be discriminated within the mPFC. (1) The ventromedial part of mPFC, comprising the pre- and infralimbic areas, receives mainly projections from the perirhinal cortex. (2) The caudal two-thirds of the dorsomedial PFC, comprising frontal area 2 and the dorsal anterior cingulate area, receives projections from the secondary visual areas, the posterior agranular insular area and the retrosplenial areas. (3) The rostral one-third of the dorsomedial PFC is the main recipient of projections from the somatosensory and motor areas and the posterior agranular insular area. The laminar distribution of cells projecting to the mPFC varies considerably in the different cortical areas, just as the laminar distribution of termination of their fibres within the mPFC does. It is concluded that the corticocortical connections corroborate with subcortical connectivity in attributing to the mediodorsal projection cortex of the rat functions which are comparable to those of certain prefrontal, premotor and anterior cingulate areas in the monkey.     

Perirhinal and parahippocampal cortices of the macaque monkey: Intrinsic projections and interconnections

We investigated the topographic and laminar organization of the intrinsic projections and interconnections of the macaque monkey perirhinal and parahippocampal cortices. Discrete anterograde tracer injections placed at various rostrocaudal and mediolateral levels in these cortices revealed extensive associational connections both within and between the perirhinal and parahippocampal cortices. Areas 35, 36rm, 36rl, 36cm, and 36cl are highly interconnected, whereas area 36d (encompassing the dorsal portion of the medial temporal pole) shares only modest connections with the rest of the perirhinal cortex. Areas TH, TFm, and TFl of the parahippocampal cortex also share an extensive network of associational connections that tend to be heaviest within a given subdivision. Area 36c of the perirhinal cortex is the main interface between the perirhinal and parahippocampal cortices. Its heaviest connections are with area 36r and the anterior aspect of area TF. The laminar organization of all these connections is typical of associational projections. Anterograde tracer experiments revealed that these projections are distributed through both deep and superficial layers, although heavier projections are directed toward the superficial layers. Results of retrograde tracer experiments suggested that the projections from caudal areas (36c or TF) to area 36r are of the feedforward type, whereas the projections from areas 36r and 36c to area TF are of the feedback type. These findings suggest that the perirhinal cortex is at a higher level than the parahippocampal cortex in the hierarchy of associational cortices. We discuss the functional implications of the organization of these extensive networks of intrinsic, associational projections.     

Heterogeneity in the Dorsal Subiculum of the Rat. Distinct Neuronal Zones Project to Different Cortical and Subcortical Targets

The aim of the present study was to relate the distribution of efferents of the dorsal subiculum to their origin along the proximodistal axis of the subiculum. The distribution of subicular projections was studied in detail by means of the sensitive anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L), and the precise origin of these projections analysed with retrogradely transported fluorescent tracers, using double- and triple-labelling protocols. Injections of PHA-L in the proximal part of the dorsal subiculum, i.e. that part which borders field CA1, result in labelling of the infralimbic, entorhinal and perirhinal cortices, the nucleus accumbens and the lateral septal region, the interanteromedial nucleus of the thalamus, the core of the nucleus gelatinosus, and the mammillary nuclei, in particular in the rostral parts of the medial nucleus. In contrast, injections in the distal part of the dorsal subiculum, i.e. that part which borders the presubiculum, give rise to labelling in the retrosplenial and postrhinal cortices, the presubiculum, the anterior thalamic complex, the shell of the nucleus gelatinosus, and the mammillary nuclei, preferentially in the caudal part of the medial nucleus. The results of injections of different retrograde tracers, simultaneously placed in two or three targets of the subicular efferents, confirm the results of the anterograde tracing experiments. Moreover, they clearly demonstrate that the population of subicular neurons which, for example, projects to the nucleus accumbens and the interanteromedial nucleus of the thalamus is almost completely segregated from the population that projects to the retrosplenial cortex and the anterior complex of the thalamus. Thus within the dorsal subiculum, populations of neurons can be differentiated so that each population projects to a unique set of target structures. These cell populations are differentially positioned along the proximo-distal axis. In view of additional evidence indicating that some of the major afferents to the subiculum are organized along the same axis, we suggest that the heterogeneity of the dorsal subiculum along the proximo-distal axis reflects a general organizational characteristic of this hippocampal field.     

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.     

Entorhinal cortex of the rat: Cytoarchitectonic subdivisions and the origin and distribution of cortical efferents

The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey. Hippocampus 7:146–183, 1997. © 1997 Wiley-Liss, Inc.     

Observations on the projections and intrinsic organization of the pigeon optic tectum: an autoradiographic study based on anterograde and retrograde, axonal and dendritic flow.

Three aspects of the labelling pattern seen after the injection of 13 different radioactive amino acids into the pigeon optic tectum have been described: The efferent projections of the optic tectum; the specific labelling of two pathways; and the dendritic organisation of tectal layer III neurons based on the retrograde and anterograde movement of label within these dendrites. Discrete injections of tritiated amino acid that involved all or only the superficial tectal layers suggested that layer III gave rise to the massive non-topographically organised and bilateral projections (fibers crossing within the decussato supraoptica ventrlis) upon the nuclei rotundus, subpraetectalis and interstitio-praetecto-subpraetectalis and to the ipsilaterally directed pathways terminating within the nuclei praetectalis, triangularis, subrotundus, dorsolateralis anterior thalami, posteroventralis and ventrolateralis thalami. Layer III neurons may also be the source of efferents to the posterior dorsolateral thalamus (the layer III pathway), the pontine grey and, bilaterally to the reticular formation and of the layer IV or tectal commisural pathway terminating within the contralateral tectal cortex. In contrast projections originating from layer II were generally topographically organised and terminated either within certain of the isthmic nuclei (n. isthmi pars parvocellularis, n. isthmo-opticus and n. semilunaris) or ran within layer I (layer I pathways) to end in the pretectum (griseum tectale) and ventral thalamus (n. ventrolateralis thalami, n. geniculatus, pars ventralis). A small projection from layer II upon the ipsilateral nucleus rotundus may also be present. Triated serine and tyrosine were found to be particularly effective in labeling perikarya as well as axons and terminals. The layer I pathway could be selectively labelled after tectal injections of 3H-GABA while the cell bodies of Ipc neurons were labelled in a retrograde fashion after tectal injections of 3H-glycine, serine or alanine. Intrinsic tectal labelling was found by correlation with Golgi material to reflect both anterograde and retrograde transport of label within dendrites of layer III cells. Anterograde movement of label indicated that the terminal portions of layer III cell dendrites ended in an orderly radial arrangement within sublayers IIb and IId, while the retrograde movement of label resulted in the labelin of layer III perikarya outside the injection field.     

Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin

The purpose of the present investigation was to examine the topographical organization of efferent projections from the cytoarchitectonic divisions of the mPFC (the medial precentral, dorsal anterior cingulate and prelimbic cortices). We also sought to determine whether the efferents from different regions within the prelimbic division were organized topographically. Anterograde transport of Phaseolus vulgaris leucoagglutinin was used to examine the efferent projections from restricted injection sites within the mPFC. Major targets of the prelimbic area were found to include prefrontal, cingulate, and perirhinal cortical structures, the dorsomedial and ventral striatum, basal forebrain nuclei, basolateral amygdala, lateral hypothalamus, mediodorsal, midline and intralaminar thalamic nuclei, periaqueductal gray region, ventral midbrain tegmentum, laterodorsal tegmental nucleus, and raphe nuclei. Previously unreported projections of the prelimbic region were also observed, including efferents to the anterior olfactory nucleus, the piriform cortex, and the pedunculopontine tegmental-cuneiform region. A topographical organization governed the efferent projections from the prelimbic area, such that the position of terminal fields within target structures was determined by the rostrocaudal, dorsoventral, and mediolateral placement of the injection sites. Efferent projections from the medial precentral and dorsal anterior cingulate divisions (dorsomedial PFC) were organized in a similar topographical fashion and produced a pattern of anterograde labeling different from that seen with prelimbic injection sites. Target structures innervated primarily by the dorsomedial PFC included certain neocortical fields (the motor, somatosensory, and visual cortices), the dorsolateral striatum, superior colliculus, deep mesencephalic nucleus, and the pontine and medullary reticular formation. Previously unreported projections to the paraoculomotor central gray area and the mesencephalic trigeminal nucleus were observed following dorsomedial PFC injections. These results indicate that the efferent projections of the mPFC are topographically organized within and across the cytoarchitectonic divisions of the medial wall cortex. The significance of topographically organized and restricted projections of the rat mPFC is discussed in light of behavioral and physiological studies indicating functional heterogeneity of this region.     

Efferent connections of the rostral portion of medial agranular cortex in rats

This study of the rostral part of medial agranular cortex (AGm) was undertaken with two principal aims in mind. First, to delineate the efferent connections of AGm and compare these with the pattern of afferents defined by us in a previous study. Second, to provide a firmer basis for anatomical and functional comparisons with cortical regions in monkeys. Autoradiographic, horseradish peroxidase, and fiber degeneration techniques were used. Rostral AGm has a variety of corticocortical connections--with lateral agranular motor cortex (AGl); visual, auditory, and somatic sensory regions; and limbic/paralimbic areas including orbital, insular, perirhinal, entorhinal, retrosplenial and presubicular fields. The projections to orbital, perirhinal and entorhinal cortices are bilateral. Thalamic projections of rostral AGm are concentrated in the ventral lateral, central lateral, paracentral, mediodorsal and ventromedial nuclei. Moderate terminal fields are consistently seen in the reticular, anteromedial, central medial, gelatinosus, parafascicular, and posterior nuclei. More caudal projections reach the central gray, superior colliculus and pontine gray. The efferents of the adjacent AGl were also examined. Although many of these overlapped those of rostral AGm, there were no efferents to visual or auditory cortex and limbic/paralimbic projections were reduced. Thalamic projections were more focused in the ventral lateral and posterior nuclei and there were no terminal fields in the central gray or superior colliculus. Based on its afferent and efferent connections, role in contralateral neglect, and the results of microstimulation studies, rostral AGm can be viewed as a multimodal association area with strong ties to the motor system. On these structural and functional grounds, rostral AGm bears certain striking resemblances to the frontal eye field, supplementary motor, and arcuate premotor areas of monkey cortex.     

Efferent connections of the prelimbic (area 32) and the infralimbic (area 25) cortices: an anterograde tracing study in the cat

The projections from the caudal part of the medial frontal cortex, encompassing the prelimbic area (PL) and the infralimbic area (IL) (Brodmann's areas 32 and 25, respectively), were studied in the cat with the anterograde autoradiographic tracing technique. The results indicate that the projection fields of IL, in contrast to those of PL, are restricted almost exclusively to limbic structures. Whereas the major thalamic projections from PL reach the mediodorsal, anteromedial, and ventromedial nuclei, the medial part of the lateral posterior nucleus, and the parataenial and reticular nuclei, and weak projections from this area are directed to the nucleus reuniens and other midline nuclei, the nucleus reuniens is the major thalamic termination field of fibers arising from IL. Cortical areas that are reached by fibers originating in PL and, to a lesser degree, also in IL, include more rostral prefrontal areas (areas 8, 6, and 12), the agranular insular, and the rostral perirhinal cortices. In contrast, cortical areas that are more strongly related to IL include the cingulate, retrosplenial, caudal entorhinal, and perirhinal cortices and the subiculum of the hippocampal formation. Another prominent output of PL concerns projections to an extensive medial part of the caudate nucleus and the ventral striatum, whereas fibers from IL only distribute most ventrally in the striatum. In the amygdaloid complex, fibers from PL were found to reach the basolateral, basomedial, and central nuclei, and fibers from IL to distribute to the medial and central nuclei. PL furthermore projects to the claustrum and the endopiriform nucleus. Other structures in the basal forebrain, including the medial septum, the nuclei of the diagonal band, the preoptic area, and the lateral and dorsal hypothalamus are densely innervated by IL and only sparsely by PL. With respect to more caudal parts of the brainstem, projections from PL and IL appeared to be essentially similar. They reach the ventral tegmental area, the periaqueductal gray, the parabrachial nucleus, and in cases of PL injections were followed as far caudally as the pons.     

Efferents from the lateral frontal cortex to spinomedullary target areas,trigeminal nuclei,and spinally projecting brainstem regions in the hedgehog tenrec

This study was done in the Madagascan lesser hedgehog tenrec, an insectivore with a very poorly differentiated neocortex. The cortical region, known to give rise to spinal projections, was injected with tracer, and the cortical efferents to brainstem and spinal cord were analyzed. Bulbar reticular fields, in addition, were identified according to their cells of origin and the laterality of their spinal projections after injection of tracer. Only few cortical fibers could be traced from the bulbar pyramid into the ipsilateral spinal cord, particularly to the lateral funiculus. The projections to the dorsal column nuclei and the classical spinally projecting brainstem regions were also weak. Faint projections were demonstrated to the nucleus of the posterior commissure and the nucleus of Darkschewitsch. In comparison to other mammals, there was no evidence that the contralateral cortico-bulbo-spinal pathway was strengthened, substituting for the almost non-existent contralateral corticospinal projection. Unlike the sensorimotor apparatus controlling limb and body movements, the brainstem regions controlling the head and neck received prominent cortical projections. Direct corticotri-geminal projections and indirect pathways were well represented. The projections to the trigeminal nuclei and the lateral reticular fields were clearly bilateral; those to the superior colliculus were predominantly ipsilateral. The corticobulbar fibers left the pyramid along its entire extent; the principal trigeminal nucleus and the dorsolateral pontine tegmentum were supplied by additional fibers of the corticotegmental tract. The lateral frontal cortex also projected densely to the dorsolateral hypothalamus, the periaqueductal gray, and the adjacent mesencephalic tegmentum, components of the emotional motor system. © 1996 Wiley-Liss, Inc.