Entorhinal Connections Research Articles

Hippocampal and subicular efferents and afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat

Available evidence suggests there is functional differentiation among hippocampal and parahippocampal subregions and along the dorsoventral (septotemporal) axis of the hippocampus. The aim of this study was to characterize and compare the efferent and afferent connections of perirhinal areas 35 and 36, postrhinal cortex, and the lateral and medial entorhinal areas (LEA and MEA) with dorsal and ventral components of the hippocampal formation (dentate gyrus, hippocampus cornu ammonis fields, and subiculum) as well as the presubiculum, and the parasubiculum. The entorhinal connections were also characterized with respect to the LEA and MEA dentate gyrus-projecting bands. In general, the entorhinal connections with the hippocampal formation are much stronger than the perirhinal and postrhinal connections. The entorhinal cortex projects strongly to all components of the hippocampal formation, whereas the perirhinal and postrhinal cortices project weakly and only to CA1 and the subiculum. In addition, the postrhinal cortex preferentially targets the dorsal CA1 and subiculum, whereas the perirhinal cortex targets ventral subiculum. Similarly, the perirhinal cortex receives more input from ventral hippocampal formation structures and the postrhinal cortex receives more input from dorsal hippocampal structures. The LEA and the MEA medial band are more strongly interconnected with ventral hippocampal structures, whereas the MEA lateral band is more interconnected with dorsal hippocampal structures. With regard to the presubiculum and parasubiculum, the postrhinal cortex and the MEA lateral band receive stronger input from the dorsal presubiculum and caudal parasubiculum. In contrast, the LEA and MEA medial bands receive stronger input from the ventral presubiculum and rostral parasubiculum.

Cognitive demands induce selective hippocampal reorganization: Arc expression in a place and response task

Place cells in the hippocampus can maintain multiple representations of a single environment and respond to physical and/or trajectory changes by remapping. Within the hippocampus there are anatomical, electrophysiological, and behavioral dissociations between the dorsal and ventral hippocampus and within dorsal CA1. Arc expression was used to measure the recruitment of ensembles across different hippocampal subregions in rats trained to utilize two different cognitive strategies while traversing an identical trajectory. This behavioral paradigm allowed for the measurement of remapping in the absence of changes in external cues, trajectory traversed (future/past), running speed, motivation, or different stages of learning. Changes in task demands induced remapping in only some hippocampal regions: reorganization of cell ensembles was observed in dorsal CA1 but not in dorsal CA3. Moreover, a gradient was found in the degree of remapping within dorsal CA1 that corresponds to entorhinal connectivity to this region. Remapping was not seen in the ventral hippocampus: neither ventral CA1 nor CA3 exhibited ensemble changes with different cognitive demands. This contrasts with findings of remapping in both the dorsal and ventral dentate gyrus using this task. The results suggest that the dorsal pole of the hippocampus is more sensitive to changes in task demands.

What Does the Anatomical Organization of the Entorhinal Cortex Tell Us?

The entorhinal cortex is commonly perceived as a major input and output structure of the hippocampal formation, entertaining the role of the nodal point of cortico-hippocampal circuits. Superficial layers receive convergent cortical information, which is relayed to structures in the hippocampus, and hippocampal output reaches deep layers of entorhinal cortex, that project back to the cortex. The finding of the grid cells in all layers and reports on interactions between deep and superficial layers indicate that this rather simplistic perception may be at fault. Therefore, an integrative approach on the entorhinal cortex, that takes into account recent additions to our knowledge database on entorhinal connectivity, is timely. We argue that layers in entorhinal cortex show different functional characteristics most likely not on the basis of strikingly different inputs or outputs, but much more likely on the basis of differences in intrinsic organization, combined with very specific sets of inputs. Here, we aim to summarize recent anatomical data supporting the notion that the traditional description of the entorhinal cortex as a layered input-output structure for the hippocampal formation does not give the deserved credit to what this structure might be contributing to the overall functions of cortico-hippocampal networks.

Functional neuroanatomy of the parahippocampal region: The lateral and medial entorhinal areas

The entorhinal cortex (EC) serves a pivotal role in corticohippocampal interactions, but a complete description of its extrinsic connections has not been presented. Here, we have summarized the cortical, subcortical, and hippocampal connections of the lateral entorhinal area (LEA) and the medial entorhinal area (MEA) in the rat. We found that the targets and relative strengths of the entorhinal connections are strikingly different for the LEA and MEA. For example, the LEA receives considerably heavier input from the piriform and insular cortices, whereas the MEA is more heavily targeted by the visual, posterior parietal, and retrosplenial cortices. Regarding subcortical connections, the LEA receives heavy input from the amygdala and olfactory structures, whereas the MEA is targeted by the dorsal thalamus, primarily the midline nuclei and also the dorsolateral and dorsoanterior thalamic nuclei. Differences in the LEA and MEA connections with hippocampal and parahippocampal structures are also described. In addition, because the EC is characterized by bands of intrinsic connectivity that span the LEA and MEA and project to different septotemporal levels of the dentate gyrus, special attention was paid to the efferents and afferents of those bands. Finally, we summarized the connections of the dorsocaudal MEA, the region in which the entorhinal "grid cells" were discovered. The subregional differences in entorhinal connectivity described here provide further evidence for functional diversity within the EC. It is hoped that these findings will inform future studies of the role of the EC in learning and memory.

Electrophysiological characterization of interlaminar entorhinal connections: an essential link for re‐entrance in the hippocampal–entorhinal system

The hippocampal formation communicates with the neocortex mainly through the adjacent entorhinal cortex. Neurons projecting to the hippocampal formation are found in the superficial layers of the entorhinal cortex and are largely segregated from the neurons receiving hippocampal output, which are located in deep entorhinal layers. We studied the communication between deep and superficial entorhinal layers in the anaesthetized rat using field potential recordings, current source density analysis and single unit measurements. We found that subiculum stimulation was able to excite entorhinal neurons in deep layers. This response was followed by current sinks in superficial layers. Both responses were subject to frequency dependent facilitation, but not depression. Selective blockade of deep layer responses also abolished subsequent superficial layer responses. This clearly demonstrates a functional deep-to-superficial layer communication in the entorhinal cortex, which can be triggered by hippocampal output. This pathway may provide a means by which processed hippocampal output is integrated or compared with new incoming information in superficial entorhinal layers, and it constitutes an important link in the process of re-entrance of activity in the hippocampal-entorhinal network, which may be important for consolidation of memories or retaining information for short periods.

Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry.

Place cells in hippocampal area CA1 may receive positional information from the intrahippocampal associative network in area CA3 or directly from the entorhinal cortex. To determine whether direct entorhinal connections support spatial firing and spatial memory, we removed all input from areas CA3 to CA1, thus isolating the CA1 area. Pyramidal cells in the isolated CA1 area developed sharp and stable place fields. Rats with an isolated CA1 area showed normal acquisition of an associative hippocampal-dependent spatial recognition task. Spatial recall was impaired. These results suggest that the hippocampus contains two functionally separable memory circuits: The direct entorhinal-CA1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA3-CA1 connectivity.

The Parahippocampal Region: Corticocortical Connectivity

The parahippocampal region, as defined in this review, comprises the cortical regions that surround the rodent hippocampus including the perirhinal, postrhinal, and entorhinal cortices. The comparable regions in the primate brain are the perirhinal, parahippocampal, and entorhinal cortices. The perirhinal and postrhinal/parahippocampal cortices provide the major polysensory input to the hippocampus through their entorhinal connections and are the recipients of differing combinations of sensory information. The differences in the perirhinal and postrhinal cortical afferentation have important functional implications, in part, because these two regions project with different terminal patterns to the entorhinal cortex. The perirhinal cortex projects preferentially to the lateral entorhinal area (LEA), and the postrhinal cortex projects preferentially to the medial entorhinal area (MEA) and the caudal portion of LEA. Although the perirhinal and postrhinal cortices provide the major cortical input to the entorhinal cortex, the entorhinal cortex itself receives some direct cortical input. An examination of the cortical afferentation of the entorhinal cortex reveals an interesting principle of connectivity among these regions; the composition of the direct neocortical input to the LEA is more similar to that of the perirhinal cortex, and the composition of the direct neocortical input to the MEA is more similar to that of the postrhinal cortex. Thus, polymodal associational input to the LEA and the MEA exhibits some segregation and is organized in parallel. The organization of intrinsic connections for each of the parahippocampal regions also contributes to the segregation of information into parallel pathways.

DISRUPTION OF TEMPORO-ENTORHINAL CONNECTIONS ABOLISHES THE FACILITATORY EFFECT OF ANGIOTENSINS ON MEMORY IN RATS

It has been found in our laboratory that the positive influence of angiotensin II (AII) and its 3–7 fragment [AII(3–7)] on learning and memory processes is mediated by the excitatory amino acids, since it was abolished by NMDA receptor antagonists. The purpose of the present study was to investigate whether bilateral disruption of glutamatergic temporo- entorhinal connections may have an influence on the facilitatory effect of both angiotensin peptides on memory motivated affectively. The bilateral transections of temporo-entorhinal connections were made in 27 male rats 10 days before testing the influence of intracerebroventricular AII and AII(3–7) injection on retrieval of a passive avoidance response. Twenty-seven additional rats served as sham-operated controls. Twenty-five lesioned and 25 sham-operated animals were accepted to the final analysis. AII and its 3–7 fragment significantly improved the retrieval process in sham-operated groups of rats. Bilateral disruption of temporo-entorhinal connections totally abolished the facilitatory effect of both angiotensins on recall of information in a passive avoidance situation. Moreover, bilateral disruption of temporo-entorhinal connections markedly but not significantly attenuated crossings of squares, evaluated in an open field test, without an influence on rearings and bar approaches. These results may suggest that in the facilitatory effect of AII and AII(3–7) on memory motivated affectively involves reciprocal glutamatergic connection between lateral entorhinal cortex and temporal cortex.

BILATERAL TRANSECTIONS OF TEMPORO–ENTORHINAL CONNECTIONS ATTENUATE VASOPRESSIN IMPROVEMENT OF MEMORY IN RATS

It has been found in our laboratory that the positive influence of vasopressin (AVP) on memory processes is mediated by excitatory amino acids, since it was abolished by NMDA receptor antagonists. The purpose of the present study was to investigate whether bilateral transections of glutamatergic temporo–entorhinal connections may have an influence on the facilitatory effect of AVP on retrieval process of a passive avoidance behaviour. The bilateral transections of temporo–entorhinal connections were made in male Wistar rats 10 days before testing of the influence of intracerebroventricular AVP (1 μg per rat) injection on memory, evaluated in a passive avoidance task. Although AVP significantly facilitated the retrieval process both in sham-operated and in lesioned groups of rats, bilateral disruption of temporo–entorhinal connections significantly attenuated the facilitatory effect of AVP on the retrieval process. Moreover, bilateral transections of temporo–entorhinal connections failed to affect motor activity, such as crossings of squares, without an influence on rearings and bar approaches evaluated in an open field test. These results may suggest that in the facilitatory effect of AVP on the retrieval process is involved a reciprocal glutamatergic connection between the lateral entorhinal cortex and the temporal cortex.

Perirhinal and postrhinal cortices of the rat: Interconnectivity and connections with the entorhinal cortex

The cortical regions dorsally adjacent to the posterior rhinal sulcus in the rat can be divided into a rostral region, the perirhinal cortex, which shares features of the monkey perirhinal cortex, and a caudal region, the postrhinal cortex, which has connectional attributes similar to the monkey parahippocampal cortex. We examined the connectivity among the rat perirhinal (areas 35 and 36), postrhinal, and entorhinal cortices by placing anterograde and retrograde tracers in all three regions. There is a dorsal-to-ventral cascade of connections in the perirhinal and entorhinal cortices. Dorsal area 36 projects strongly to ventral area 36, and ventral area 36 projects strongly to area 35. The return projections are substantially weaker. The cascade continues with the perirhinal to entorhinal connections. Area 35 is more strongly interconnected with the entorhinal cortex, ventral area 36 somewhat less strongly, and dorsal area 36 projects only weakly to the entorhinal cortex. The postrhinal-to-perirhinal connections also follow this general pattern. The postrhinal cortex is more heavily connected with dorsal area 36 than with ventral area 36 and is more heavily connected with area 36 than with area 35. The rostral portion of the postrhinal cortex has the strongest connections with the perirhinal cortex. Like in the monkey, the perirhinal and postrhinal cortices have different patterns of projections to the entorhinal cortex. The perirhinal cortex is preferentially connected with the rostrolateral portion of the entorhinal cortex. The postrhinal cortex projects to a part of this same region but is also connected to caudal and redial portions of the entorhinal cortex. The perirhinal and postrhinal projections to the entorhinal cortex originate in layers III and V and terminate preferentially in layers II and III.

The organization of the intrinsic and entorhinal connections of the rat presubiculum

The organization of the intrinsic and entorhinal connections of the rat presubiculum

Entorhinal transplants and spatial memory abilities in rats

Transplants of embryonic entorhinal tissues, placed into the angular bundle region of adult rats, innervate appropriate areas of the host hippocampal formation and amygdala, provided that native entorhinal connections have been destroyed. In the present study, transplants were examined for their ability to restore spatial memory abilities which are lost following the bilateral destruction of native entorhinal connections. Animals were tested for their ability to perform an 8-arm radial maze task, for spontaneous alternation in a T-maze, and for their ability to learn to alternate in a T-maze for a food reward. Animals with lesions, and those with lesions + implants, remained impaired on all 3 tasks examined for as long as 6 months postimplantation. During this time, no transplant-induced behavioral recovery was observed, although behavioral stabilization was observed on the spontaneous alternation task at 6 months post-transplantation. The data suggest that these transplants may be limited in their ability to restore functions which are highly dependent upon the anatomical integrity of the damaged circuits and the precise organization of information flow through the damaged area.