The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network.

Converging evidence suggests that each parahippocampal and hippocampal subregion contributes uniquely to the encoding, consolidation and retrieval of declarative memories, but their precise roles remain elusive. Current functional thinking does not fully incorporate the intricately connected networks that link these subregions, owing to their organizational complexity; however, such detailed anatomical knowledge is of pivotal importance for comprehending the unique functional contribution of each subregion. We have therefore developed an interactive diagram with the aim to display all of the currently known anatomical connections of the rat parahippocampal-hippocampal network. In this Review, we integrate the existing anatomical knowledge into a concise description of this network and discuss the functional implications of some relatively underexposed connections.

Early differences in dorsal hippocampal metabolite levels in males but not females in a transgenic rat model of Alzheimer's disease.

McGill-R-Thy1-APP rats express the human amyloid precursor protein carrying the Swedish and Indiana mutations. We examined the neurochemical content of the dorsal hippocampus in three-months-old male and female transgenic rats and healthy age- and gender-matched controls using in vivo (1)H MRS in order to assess early metabolite alterations and whether these were similar for both genders. Whereas male and female controls had similar levels of all metabolites, differences were evident between male and female McGill-R-Thy1-APP rats. Compared with McGill-R-Thy1-APP females, McGill-R-Thy1-APP males had lower levels of myo-inositol and N-acetylaspartate (NAA). No differences in metabolite levels were evident when female control and McGill-R-Thy1-APP rats were compared, whereas McGill-R-Thy1-APP males had lower levels of glutamate, NAA and total choline compared with male controls. In addition to metabolite concentrations, metabolite ratios are reported as these are widely used. The results from this preliminary study demonstrate early metabolite alterations in the dorsal hippocampus of males in this rat model of Alzheimer's disease, and imply that very early possible neurochemical markers of the disease are different for males and females.

The thalamic midline nucleus reuniens: potential relevance for schizophrenia and epilepsy.

Anatomical, electrophysiological and behavioral studies in rodents have shown that the thalamic midline nucleus reuniens (RE) is a crucial link in the communication between hippocampal formation (HIP, i.e., CA1, subiculum) and medial prefrontal cortex (mPFC), important structures for cognitive and executive functions. A common feature in neurodevelopmental and neurodegenerative brain diseases is a dysfunctional connectivity/communication between HIP and mPFC, and disturbances in the cognitive domain. Therefore, it is assumed that aberrant functioning of RE may contribute to behavioral/cognitive impairments in brain diseases characterized by cortico-thalamo-hippocampal circuit dysfunctions. In the human brain the connections of RE are largely unknown. Yet, recent studies have found important similarities in the functional connectivity of HIP-mPFC-RE in humans and rodents, making cautious extrapolating experimental findings from animal models to humans justifiable. The focus of this review is on a potential involvement of RE in schizophrenia and epilepsy.

Entorhinal-hippocampal interactions revealed by real-time imaging.

The entorhinal cortex provides the major cortical input to the hippocampus, and both structures have been implicated in memory processes. The dynamics of neuronal circuits in the entorhinal-hippocampal system were studied in slices by optical imaging with high spatial and temporal resolution. Reverberation of neural activity was detected in the entorhinal cortex and was more prominent when the inhibition due to gamma-aminobutyric acid was slightly suppressed. Neural activity was transferred in a frequency-dependent way from the entorhinal cortex to the hippocampus. The entorhinal neuronal circuit could contribute to memory processes by holding information and selectively gating the entry of information into the hippocampus.

Distinct brain systems underlie the processing of valence and arousal of affective pictures.

Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural activation in healthy females (N=23) to affective pictures using a 2 (Valence) x 2 (Arousal) design. Results show that arousal was preferentially processed by middle temporal gyrus, hippocampus and ventrolateral prefrontal cortex. Regions responding to negative valence included visual and lateral prefrontal regions, positive valence activated middle temporal and orbitofrontal areas. Importantly, distinct arousal-by-valence interactions were present in anterior insula (negative pictures), and in occipital cortex, parahippocampal gyrus and posterior cingulate (positive pictures). These data demonstrate that the brain not only differentiates between valence and arousal but also responds to specific combinations of these two, thereby highlighting the sophisticated nature of emotion processing in (female) human subjects.

Contacts between medial and lateral perforant pathway fibers and parvalbumin expressing neurons in the subiculum of the rat.

The entorhinal cortex (EC) projects via the perforant pathway to all subfields in the hippocampal formation. One can distinguish medial and lateral components in the pathway, originating in corresponding medial and lateral subdivisions of EC. We analyzed the innervation by medial and lateral perforant pathway fibers of parvalbumin-expressing neurons in the subiculum. A neuroanatomical tracer (biotinylated dextran amine, BDA) was stereotaxically injected in the medial or lateral entorhinal cortex, thus selectively labeling either perforant pathway component. Transport was allowed for 1 week. Transported BDA was detected with streptavidin-Alexa Fluor 488. Parvalbumin neurons were visualized via immunofluorescence histochemistry, using the fluorochrome Alexa Fluor 594. Via a random systematic sampling scheme using a two-channel, sequential-mode confocal laser scanning procedure, we obtained image series at high magnification from the molecular layer of the subiculum. Labeled entorhinal fibers and parvalbumin-expressing structures were three dimensionally (3D) reconstructed using computer software. Further computer analysis revealed that approximately 16% of the 3D objects ('boutons') of BDA-labeled fibers was engaged in contacts with parvalbumin-immunostained dendrites in the subiculum. Both medial and lateral perforant pathway fibers and their boutons formed such appositions. Contacts are suggestive for synapses. We found no significant differences between the medial and lateral components in the relative numbers of contacts. Thus, the medial and lateral subdivisions of the entorhinal cortex similarly tune the firing of principal neurons in the subiculum by way of parvalbumin positive interneurons in their respective terminal zones.

Does assimilation into schemas involve systems or cellular consolidation? It's not just time.

A comment by Rudy and Sutherland [Rudy, J. R., & Sutherland, R. J. (2008). Is it systems or cellular consolidation? Time will tell. An alternative interpretation of the Morris Group's recent Science Paper. Neurobiology of Learning and Memory] has suggested an alternative account of recent findings concerning very rapid systems consolidation as described in a recent paper by Tse et al [Tse, D., Langston, R. F., Kakeyama, M., Bethus, I., Spooner, P. A., & Wood, E. R., et al. (2007). Schemas and memory consolidation. Science, 316, 76-82]. This is to suppose that excitotoxic lesions of the hippocampus cause transient disruptive neural activity outside the target structure that interferes with cellular consolidation in the cortex. We disagree with this alternative interpretation of our findings and cite relevant data in our original paper indicating why this proposal is unlikely. Various predictions of the two accounts are nonetheless outlined, together with the types of experiments needed to resolve the issue of whether systems consolidation can occur very rapidly when guided by activated neural schemas.

Nonlinear changes in brain activity during continuous word repetition: an event-related multiparametric functional MR imaging study.

BACKGROUND AND PURPOSE: Changes in brain activation as a function of continuous multiparametric word recognition have not been studied before by using functional MR imaging (fMRI), to our knowledge. Our aim was to identify linear changes in brain activation and, what is more interesting, nonlinear changes in brain activation as a function of extended word repetition. MATERIALS AND METHODS: Fifteen healthy young right-handed individuals participated in this study. An event-related extended continuous word-recognition task with 30 target words was used to study the parametric effect of word recognition on brain activation. Word-recognition-related brain activation was studied as a function of 9 word repetitions. fMRI data were analyzed with a general linear model with regressors for linearly changing signal intensity and nonlinearly changing signal intensity, according to group average reaction time (RT) and individual RTs. RESULTS: A network generally associated with episodic memory recognition showed either constant or linearly decreasing brain activation as a function of word repetition. Furthermore, both anterior and posterior cingulate cortices and the left middle frontal gyrus followed the nonlinear curve of the group RT, whereas the anterior cingulate cortex was also associated with individual RT. CONCLUSION: Linear alteration in brain activation as a function of word repetition explained most changes in blood oxygen level-dependent signal intensity. Using a hierarchically orthogonalized model, we found evidence for nonlinear activation associated with both group and individual RTs.

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat.

The nucleus reuniens (RE) and entorhinal cortex (EC) provide monosynaptic excitatory inputs to the apical dendrites of pyramidal cells and to interneurons with dendrites in stratum lacunosum moleculare (LM) of hippocampal field CA1. However, whether the RE and EC inputs interact at the cellular level is unknown. In this electrophysiological in vivo study, low-frequency stimulation was used to selectively activate each projection at its origin; field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1. We applied (1) paired pulses to RE or EC, (2) combined paired pulses to RE and EC, and (3) simultaneously paired pulses to RE/EC. The main findings are that: (a) stimulation of either RE- or EC-evoked subthreshold fEPSPs, displaying paired pulse facilitation (PPF), (b) subthreshold fEPSPs evoked by combined stimulation did not display heterosynaptic PPF, and (c) simultaneous stimulation of RE/EC resulted in enhanced subthreshold fEPSPs in proximal LM displaying a nonlinear interaction. CSD analyses of RE/EC-evoked depth profiles revealed a nonlinear enlargement of the 'LM sink-radiatum source' configuration and the appearance of an additional small sink-source pair close to stratum pyramidale, likely reflecting (peri)somatic inhibition. The nonlinear interaction between both inputs indicates that RE and EC axons form synapses, at least partly, onto the same dendritic compartments of CA1 pyramidal cells. We propose that low-frequency activation of the RE-CA1 input facilitates the entorhinal-hippocampal dialogue, and may synchronize the neocortical-hippocampal slow oscillation which is relevant for hippocampal-dependent memory consolidation.

Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks.

The cingulate cortex is a functionally and morphologically heterogeneous cortical area comprising a number of interconnected subregions. To date, the exact anatomy of intracingulate connections has not been studied in detail. In the present study we aimed to determine the topographical and laminar characteristics of intrinsic cingulate connections in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. For assessment of these data we further refined and compared the existing cytoarchitectonic descriptions of the two major cingulate constituents, the anterior cingulate and retrosplenial cortices. The results of this study demonstrate that rostral areas, i.e. the infralimbic and prelimbic cortices and the rostral one third of the dorsal anterior cingulate cortex are primarily interconnected with each other and not with other cingulate areas. The caudal two thirds of the dorsal anterior cingulate cortex project to the caudal part of the ventral anterior cingulate cortex, whereas the entire ventral anterior cingulate cortex projects to only the mid-rostro-caudal part of the dorsal anterior cingulate cortex. Dense reciprocal connections exist between the remaining, i.e. the supracallosal parts of the anterior cingulate and retrosplenial cortices with a general rostro-caudal topography, in the sense that the rostral part of the anterior cingulate cortex and caudal part of the retrosplenial cortex are interconnected and the same holds true for the caudal part of the anterior cingulate cortex and rostral part of the retrosplenial cortex. This topographical pattern of intracingulate connections relates to the results of several functional studies, suggesting that specific cingulate functions depend on a number of interconnected cingulate subregions. Through their intricate associational connections, these subregions form functionally segregated networks.

Entorhinal projections terminate onto principal neurons and interneurons in the subiculum: a quantitative electron microscopical analysis in the rat.

The synaptic organization of projections to the subiculum from superficial layers of the lateral and medial entorhinal cortex was analyzed in the rat, using anterograde neuroanatomical tracing followed by electron microscopical quantification. Our aim was to assess the synaptic organization and whether the two projection components (lateral, medial) within the perforant pathway are qualitatively and quantitatively similar with respect to the types of synapses formed and with respect to the postsynaptic targets of these entorhinal projections. The tracer biotinylated dextran amine (BDA) was injected into the lateral and medial entorhinal cortex, respectively, and resulting anterograde labeling in the subiculum was studied. For each of the two projection components, we analyzed in four animals (2 x 2) a total of 100 synapses/animal with respect to features of the synapse type, i.e. asymmetrical or symmetrical, as well as regarding their postsynaptic target, i.e. dendritic shaft or spine. No clear differences were observed between the two pathways. The majority of the synapses were of the asymmetrical type, making contact with spines (78%) or with dendritic shafts (14%). A low percentage of symmetrical synapses targeted dendritic shafts (4.2%) or spines (1.3%). About 2.5% of the synapses remained undetermined. The findings indicate that the majority of entorhinal fibers reaching the subiculum exert an excitatory influence primarily onto principal neurons, with a much smaller feed forward inhibitory component. Only a small percentage of entorhinal fibers in the subiculum appears to be inhibitory, largely influencing interneurons.

Regional and laminar organization of projections from the presubiculum and parasubiculum to the entorhinal cortex: an anterograde tracing study in the rat.

The regional and laminar organization of the projections from the presubiculum and the parasubiculum to the entorhinal cortex was analyzed in the rat with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). The projections from the presubiculum were bilateral and confined to layers III and I of the medial entorhinal area (MEA). Both the ispi- and the contralateral projections showed similar distributions and were almost of equal density. Projections to layer III of the entorhinal cortex arose predominantly from superficial layers of the presubiculum, whereas the fibers that reach layer I of the entorhinal cortex appear to originate preferentially from the deep layers of the presubiculum. These fibers also appeared to innervate weakly layer II of MEA. The parasubiculum distributed projections not only to MEA but also to the lateral entorhinal area (LEA), innervating layer II selectively. The innervation of LEA was quite dense and extensive. Very weak projections from the parasubiculum to the contralateral entorhinal cortex were observed in this study. The position of the terminal plexus in the entorhinal cortex was determined by the point of origin along both the dorsoventral and transverse or proximodistal axes of the presubiculum and parasubiculum. Projections from the presubiculum and parasubiculum entered the entorhinal cortex at the level of the injection, or slightly ventral to it, and the main terminal field was always present ventrally to the injection site. The dorsoventral axis of origin thus corresponded to a similarly oriented axis of termination in the entorhinal cortex. The distribution in relation to the origin along the transverse axis was more complex, and differences between the presubiculum and parasubiculum were present. The proximal presubiculum, i.e., the part closest to the subiculum, projected to the most lateral part of MEA and the central part of the presubiculum sent fibers to the most medial part of MEA. The distal part of the presubiculum, i.e., the part that borders the parasubiculum, projected to the central part of MEA. Projections from the portion of the parasubiculum directly adjacent to the presubiculum, the so-called proximal parasubiculum, reached medial parts of MEA, and those originating in the central part distributed preferentially to lateral parts of MEA and adjacent medial parts of LEA. The distal part of the parasubiculum that borders the entorhinal cortex projected mainly to almost the full mediolateral extent of LEA.(ABSTRACT TRUNCATED AT 400 WORDS)

Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex.

The topographic and laminar organization of entorhinal projections to the dentate gyrus, hippocampus, and subicular complex was investigated in the Macaca fascicularis monkey. Injections of 3H-amino acids were placed at various positions within the entorhinal cortex and the distribution of anterogradely labeled fibers and terminals within the other fields of the hippocampal formation was determined. Injections of the retrograde tracers Fast blue, Diamidino yellow, and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were also placed into the dentate gyrus, hippocampus, and subicular complex, and the distribution of retrogradely labeled cells in the entorhinal cortex was plotted using a computer-aided digitizing system. The entorhinal cortex gave rise to projections that terminated in the subiculum, in the CA1, CA2, and CA3 fields of the hippocampus, and in the dentate gyrus. Projections to the dentate gyrus, and fields CA3 and CA2 of the hippocampus, originated preferentially in layers II and VI of the entorhinal cortex whereas projections to CA1 and to the subiculum originated mainly in layers III and V. Anterograde tracing experiments demonstrated that all regions of the entorhinal cortex project to the outer two-thirds of the molecular layer of the dentate gyrus and to much of the radial extent of the stratum lacunosum-moleculare of CA3 and CA2. While the terminal distributions of entorhinal projections to the dentate gyrus, CA3, and CA2 were not as clearly laminated as in the rat, projections from rostral levels of the entorhinal cortex preferentially innervated the outer portion of the molecular layer and stratum lacunosum-moleculare, whereas more caudal levels of the entorhinal cortex projected relatively more heavily to the deeper portions of the entorhinal terminal zones. The entorhinal projection to the CA1 field of the hippocampus and to the subiculum followed a transverse rather than radial gradient of distribution. Rostral levels of the entorhinal cortex terminated most heavily at the border of CA1 and the subiculum. More caudal levels of the entorhinal cortex projected to progressively more distal portions of the subiculum (towards the presubiculum) and more proximal portions of CA1 (towards CA2). Lateral portions of the entorhinal cortex projected to caudal levels of the recipient fields and more medial parts of the entorhinal cortex projected to progressively more rostral portions of the fields.

Connections of the parahippocampal cortex in the cat. III. Cortical and thalamic efferents.

To study the distribution of the cortical and thalamic efferent projections from the parahippocampal cortex in the cat, a series of injections of anterogradely transported radioactively labeled amino acids were placed in different parts of the entorhinal and perirhinal cortices. Subsequently, some of the identified cortical and thalamic target areas were injected with retrograde tracers such as wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) or with a fluorescent tracer--fast blue or nuclear yellow--in order to disclose the laminar origin of the parahippocampal efferent projections. The results indicate that the parahippocampal cortex gives rise to widespread projections to the association cortex, and, to a lesser extent, sends fibers to the limbic cortex and the primary sensory cortex. These projections arise mainly from the deep layers of the parahippocampal cortex and terminate predominantly in superficial layers of the cortex, with a preference for layer I. Within the cortical projections a medial-to-lateral topography could be observed such that the entorhinal cortex projects predominantly to the allocortical and periallocortical limbic areas, including parts of the subicular complex, the ventral retrosplenial and the infralimbic cortices, and olfactory related areas--i.e., the olfactory bulb, the anterior olfactory nucleus, the prepiriform cortex, and the ventral tenia tecta. The more lateral parts of the parahippocampal cortex, which surround the posterior rhinal sulcus, project in addition to extensive parts of the paralimbic association cortex that include the proisocortical cingular, prelimbic, orbitofrontal, and agranular and granular insular cortices. The most lateral portion of the parahippocampal cortex, the perirhinal cortex, furthermore issues projections to widespread neocortical areas on the lateral and medial aspects of the hemisphere that constitute part of the parasensory association cortex. Weak-to-moderate projections are found to the cortex of the middle suprasylvian and anterior ectosylvian sulci, as well as the cruciate and splenial sulci, all of which have been reported to constitute sensory convergence areas. The most marked projections from the perirhinal cortex reach a zone of neocortex directly lateral to the perirhinal cortex including ventral parts of the posterior sylvian, posterior ectosylvian, posterior suprasylvian, and lateral gyri. These projections appear to be topographically organized such that rostral parts of the perirhinal cortex project more rostrally, and more caudal parts of the perirhinal cortex project to more caudal parts of this cortical zone.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections of the parahippocampal cortex in the cat. IV. Subcortical efferents.

The present report deals with the projections from the entorhinal and perirhinal cortices to subcortical forebrain structures and the brainstem in the cat. By using anterograde and retrograde tracing techniques, it could be demonstrated that the entire mediolateral extent of the parahippocampal cortex issues prominent projections to the dorsal and ventral striatum, the amygdala, and the claustrum. In addition, the entorhinal cortex sends projections to the septum and the diagonal band of Broca. Only the perirhinal cortex gives rise to a weak projection to the dorsolateral periaquaductal gray and the ventral pontine region. The major proportion of the subcortical projections originates in the perirhinal cortex and the lateral entorhinal cortex, whereas the medial entorhinal cortex has a much sparser output and sends no fibers to the amygdala. The subcortical projections from both the entorhinal cortex and the perirhinal cortex arise mostly from their deep layers. It was further found that these projections are topographically organized along the mediolateral axis of the parahippocampal cortex. This mediolateral axis is related to a ventrolateral to dorsomedial axis in the septum, a mediolateral axis in the amygdala and the ventral striatum, and a ventrodorsal coordinate in the dorsal striatum and the claustrum. A further topography was observed in the projections from the perirhinal cortex to the lateral amygdaloid nucleus. A rostrocaudal axis in the perirhinal cortex corresponds to a mediolateral axis in the lateral amygdaloid nucleus. The present observations are compared with data concerning the connectivity of the parahippocampal cortex with the hippocampal formation and other cortical structures. It is suggested that the parahippocampal cortex in the cat may be conceptualized as an interface between the hippocampal formation and several subcortical structures in the realm of the limbic and motor systems.

Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin.

Projections of the hippocampal formation to the prefrontal cortex were visualized in the rat by means of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. These projections distribute only to the prelimbic and the medial orbital cortices and arise exclusively from restricted portions of field CA1 of the Ammon's horn and the subiculum. The most dorsal portion of CA1 does not contribute fibers to this projection. In the subiculum, its origin is restricted to the proximal half, i.e., the portion that directly borders field CA1. Fibers from field CA1 and the subiculum have comparable distribution patterns in the prelimbic and medial orbital cortices. The density and distribution in the prefrontal cortex of the projections from the proximal portion of the subiculum depends on the location of the injections along the dorsoventral axis of the hippocampal formation: the intermediate portion of the subiculum projects more densely and diffusely than its dorsal and ventral portions. In the prelimbic cortex, labeled fibers are present in all layers, showing marked morphological differences in deep versus superficial layers. In layers V and VI, most of the fibers are vertically oriented, while in layers II and III they are short and oriented towards the pial surface. Although no clear differences in terminal distribution were observed along the rostrocaudal extent of the prelimbic cortex, its dorsal and ventral portions show different innervation patterns. In the ventral portion of the prelimbic cortex, varicose fibers and terminal arborizations were present in all cortical layers, deep (V and VI) as well as superficial (II and III). In its dorsal part, the innervation was less dense and mostly present in the deep layers (V and VI). The fiber and terminal distribution in the medial orbital cortex was diffuse in all layers with a slight preference for layers deep to layer II.

Subicular efferents are organized mostly as parallel projections: a double-labeling, retrograde-tracing study in the rat.

To understand the functional relevance of the subiculum as a major distributor of hippocampally processed information, detailed information about its neuronal organization is necessary. A striking feature of the subiculum is that it can be divided into four different areas, each characterized by a specific set of efferent connections. To establish whether the different areas of the subiculum are similar with respect to the organization of the origin of their respective efferents, the double-fluorescence retrograde-tracing technique was used to study the degree of collateralization. Because CA1 gives rise to a major input to the subiculum but also projects to some of the targets reached by subicular projections, we compared the subicular degree of collateralization with that of CA1. Throughout CA1, the percentages of double-labeled cells were high, ranging from 17% to 39%. In contrast, the percentages of double-labeled cells in the subiculum were much lower, ranging from 0% to 12%, and no differences were noted between the four areas of the subiculum. This indicates that the four regions of the subiculum are organized in the same way with regard to the output connectivity. Because all four different regions of the subiculum share this paucity of collateralized projections, we conclude that subicular outputs generally originate as parallel projections. This characteristic organization is in line with a proposed function of the subiculum in information storage.

Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat.

The projections of the entorhinal and perirhinal cortices to the hippocampus in the cat have been studied with retrograde and anterograde tracing techniques. Retrogradely transported tracers, which were injected at different levels along the septotemporal longitudinal hippocampal axis, result in labeled neurons in superficial entorhinal cortical layers II and III. Occasionally, labeled cells were also observed in the deepest entorhinal layer as well as in the superficial layers of the perirhinal area 35. It could further be shown that labeled neurons located superficially in the entorhinal cortex are topographically distributed in a lateromedial gradient, which corresponds to a septotemporal gradient along the longitudinal axis of the hippocampus. This topographical organization of the entorhinal-hippocampal projection system could be substantiated by the use of anterograde tracing of radioactively labeled amino acids. Injections in the entorhinal cortex produce labeled fibers in the hippocampus. Injections in the perirhinal area 35 result also in labeling over the hippocampus, whereas area 36 does not seem to distribute fibers to the hippocampus. As anticipated from the results of the retrograde tracing experiments, injections located laterally, in or close to the posterior rhinal sulcus, produce prominent labeling over the septal pole of the hippocampus, whereas progressively more medially located injections result in progressively more temporally located labeling. This topographical distribution of perforant path fibers along the septotemporal axis of the hippocampus, which is related to a lateromedial axis in the entorhinal cortex, has been observed following injections in the lateral entorhinal area (LEA) as well as in the medial entorhinal area (MEA). The present observations are discussed in regard of other connectional and putative functional differences between the septal and temporal hippocampus.

Projection from the nucleus reuniens thalami to the hippocampal region: light and electron microscopic tracing study in the rat with the anterograde tracer Phaseolus vulgaris-leucoagglutinin.

In order to study the morphological substrate of possible thalamic influence on the cells of origin and area of termination of the projection from the entorhinal cortex to the hippocampal formation, we examined the pathways, terminal distribution, and ultrastructure of the innervation of the hippocampal formation and parahippocampal region by the nucleus reuniens of the thalamus (NRT). We employed anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Injections of PHA-L in the NRT produce fiber and terminal labeling in the stratum lacunosum-moleculare of field CA1 of the hippocampus, the molecular layer of the subiculum, layers I and III/IV of the dorsal subdivision of the lateral entorhinal area (DLEA), and layers I and III-VI of the ventral lateral (VLEA) and medial (MEA) divisions of the entorhinal cortex. Terminal labeling is most dense in the stratum lacunosum-moleculare of field CA1, the molecular layer of the ventral part of the subiculum, MEA, and layer I of the perirhinal cortex. In layer I of the caudal part of DLEA and in MEA, terminal labeling is present in clusters. Injections in the rostral half of the NRT produce the same distribution in the hippocampal region as those in the caudal half of the NRT, although the projections from the rostral half of the NRT are much stronger. A topographical organization is present in the projections from the head of the NRT, so that the dorsal part projects predominantly to dorsal parts of field CA1 and the subiculum and to lateral parts of the entorhinal cortex, whereas the ventral part projects in greatest volume to ventral parts of field CA1 and the subiculum and to medial parts of the entorhinal cortex. The distribution of the reuniens fibers coursing in the cingulate bundle was determined by comparing cases with and without transections of this bundle. The fibers carried by the cingulate bundle exclusively innervate field CA1 of the hippocampus, the dorsal part of the subiculum, and the presubiculum and parasubiculum. They participate in the innervation of the ventral part of the subiculum and MEA. Electron microscopy was used to visualize the axon terminals of PHA-L-labeled reuniens fibers. These terminals possess spherical synaptic vesicles and form asymmetric synaptic contacts with dendritic spines or with thin shafts of spinous dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections of the parahippocampal cortex in the cat. V. Intrinsic connections; comments on input/output connections with the hippocampus.

The present report is the last in a series of papers on the connectivity of the parahippocampal cortex in the cat, which in this species is considered to be composed of the entorhinal and perirhinal cortices. Injections of anterogradely transported tritiated amino acids and the retrograde tracers HRP, WGA-HRP, fast blue, or nuclear yellow were placed within the limits of the parahippocampal cortex. An analysis was made of the resulting pattern of anterograde labeling and of the distribution of retrogradely labeled neurons within the parahippocampal cortex. It appears that within the parahippocampal cortex of the cat a framework exists, which is composed of longitudinal and transverse connections, organized according to three principles: Medially directed projections originate mostly in superficial layers, whereas laterally directed fibers come from deep layers. The longitudinal connections span the entire rostrocaudal extent of the parahippocampal cortex, whereas the mediolateral extent of the transverse connections is in general more restricted. Based on the organization of these longitudinal and transverse connections four longitudinal zones are recognized. The lateral entorhinal cortex (LEA) projects both within the entorhinal cortex and to the perirhinal cortex, whereas the intrinsic projections of the medial entorhinal cortex (MEA) are confined to the entorhinal cortex. These results are discussed in conjunction with the main organizational features of the afferent and efferent connections of the parahippocampal cortex of the cat. The premise is made that the cytoarchitectonically defined subdivisions of the cortex can be grouped into four areas, each with its own set of fiber connections and subserving different functional roles. A lateral area, constituted by the perirhinal areas 35 and 36, and the caudally adjacent postsplenial cortex, serves as a peripheral area through which the rest of the parahippocampal cortex--i.e., LEA and MEA, and ultimately the hippocampal formation--reciprocally communicates with extensive neocortical, subcortical, and thalamic regions associated with higher-order behavior. The medial part of LEA, constituted by the ventrolateral (VLEA) and ventromedial (VMEA) divisions, has reciprocal connections with the hippocampal formation and with the cortex, partly via the perirhinal cortex, and is connected with a number of subcortical structures such as the amygdala and the striatum.(ABSTRACT TRUNCATED AT 400 WORDS)