Perirhinal Cortex and Associated Cortical Areas

Research on learning and memory has confirmed that the structures within the hippocampal formation, including the dentate gyrus, Ammon's horn, and the subiculum play an important role in certain kinds of memory. Memory functions are also subserved by nearby cortical regions that are closely interconnected with the hippocampal formation. These regions, called the parahippocampal region, include the perirhinal, parahippocampal, and entorhinal cortices together with the parasubiculum and the presubiculum (The postrhinal cortex in the rat brain is analogous to the primate parahippocampal cortex [Burwell and Amaral, 1998a]). Of these regions, the perirhinal cortex has received the most emphasis from researchers on memory. However, the individual structures within the parahippocampal region are so strongly interconnected with one another and with the hippocampal structures that it is difficult to discuss one without addressing the others. With interest in all of these regions on the rise, it is likely that future research will identify roles for each in memory functions.

In the basic scheme of cortico-hippocampal circuitry, highly processed cortical input reaches the entorhinal cortex though projections from the perirhinal and parahippocampal cortices. The entorhinal cortex projects primarily to the dentate gyrus, the input structure of the hippocampal formation. The output structure of the hippocampal formation, the subiculum, projects back to the entorhinal cortex directly and indirectly through the presubiculum and parasubiculum. This basic circuitry, however, is augmented by additional pathways. Each parahippocampal structure, including the perirhinal cortex, is interconnected with at least two hippocampal-formation structures. Moreover, all parts of the parahippocampal region are highly interconnected with cortical and subcortical regions.

Cortical Connections

The cortical afferentation of the perirhinal cortex is consistent with a role in higher-level visual perception, such as the identification of objects based on complex features such as size, shape, color, and pattern. Most of its input arises from sensory associational regions. In primates the input is weighted toward higher-order visual areas. The perirhinal cortex also receives substantial input from polymodal associational regions; a large proportion arises from its neighbor, the parahippocampal cortex, and other temporal regions. The rest arises roughly equally from prefrontal, frontal, and insular regions. In the primate brain there is no input to perirhinal cortex from the retrosplenial cortex, a structure that may play a role in visuospatial functions. The connectivity of the parahippocampal cortex suggests a role in visuo-spatial functions. A large input to the parahippocampal cortex arises in the cingulate and retrosplenial cortices, and the projections are reciprocal. There is also substantial input from the posterior parietal cortex, a region that seems to contribute to visuospatial attention. The parahippocampal cortex is not solely a visual region, however; one of its subdivisions is connected with unimodal auditory regions. The region is also connected with the orbital frontal cortex.

The perirhinal and parahippocampal cortices provide the major cortical input to the entorhinal cortex. The connections are organized such that the perirhinal cortex projects to rostral portions of the entorhinal cortex and the parahippocampal cortex projects to caudal portions. The entorhinal cortex also receives direct cortical input arising in the piriform cortex, frontal and prefrontal regions, the insular cortex, the inferior and temporal gyrus, and the retrosplenial cortex.

The presubiculum and parasubiculum are reciprocally connected with the entorhinal cortex, but they are also interconnected with several neocortical regions. Input to the presubiculum includes the dorsolateral prefrontal cortex, superior and inferior temporal gyrus, cingulate and retrosplenial cortex, and parietal cortex. The parasubiculum appears to receive input from the inferior temporal gyrus and dorsolateral prefrontal cortex.

Subcortical Connections

With the advent of modern neuroanatomical tract tracing methods, subcortical connectivity has become particularly useful in the attempt to understand brain functions. Perirhinal subcortical connections are extensive and include structures within the basal ganglia, claustrum, and thalamus, including the pulvinar and mediaodorsal nucleus, basal forebrain, and amygdala. There are extensive and sometimes reciprocal perirhinal conections with basal-forebrain structures, including the medial septum, the diagonal band of Broca, and the substantia innominata.

The perirhinal connections with the amygdala have received much interest because of a possible role in emotional memory. The perirhinal cortex is most strongly interconnected with the deep amygdaloid nuclei, including the lateral, basal, and accessory basal nuclei. The perirhinal cortex connections with subdivisions of the amygdala are stronger than those with any other region in temporal cortex, including the parahippocampal cortex.

The parahippocampal cortex, like the perirhinal cortex, is widely connected with subcortical structures. These include the basal ganglia, particularly the head, body, and tail of the caudate nucleus, the nucleus accumbens, and the ventral putamen; septal regions, including the medial septum, the diagonal band of Broca, and the substantia innominata; and several thalamic nuclei, including the medial pulvinar, the medial dorsal, and the lateral dorsal. The parahippocampal cortex is also connected with the amydala, particularly the basal nucleus.

Not to be overshadowed, the entorhinal cortex also receives direct input from multiple subcortical regions, including the basal forebrain, claustrum, amygdala, thalamus, hypothalamus, and brain stem. The input from the claustrum, especially the ventral, visual portion is relatively strong. Most of the subcortical structures that project to the entorhinal cortex also project to fields of the hippocampal formation.

The entorhinal cortex projects to the lateral, basal, and accessory basal nuclei of the amygdala and the periramygdaloid cortex. All parts of the entorhinal cortex receive amygdalar input, but the rostral subfields, those most strongly interconnected with the perirhinal cortex, are more strongly interconnected with the amygdala than the caudal subfields. The major thalamic input arises in midline nuclei, particularly the nucleus reunions.

The presubiculum and parasubiculum also receive direct input from the lateral, basal, and basomedial nuclei of the amygdala. Other subcortical connections include the laterodorsal thalamic nucleus, the midline thalamic nuclei, the ventral tegmental area, and the dorsal raphe nucleus.

Hippocampal Connections

The entorhinal cortex provides the major input to the hippocampal formation through the perforant pathway. To summarize the projection, all regions of the entorhinal cortex project to the outer two-thirds of the molecular layer of the dentate gyrus. The region also projects to fields CA3, CA2, and CA1 of the hippocampus proper (Ammon's horn) and to the subiculum. The projections to the dentate gyrus, CA3, and CA2 originate in layer II of the entorhinal cortex, whereas the projections to CA1 and the subiculum originate in layer III. The entorhinal projections to the CA1 and subiculum exhibit a certain topography such that the rostral and caudal entorhinal cortex project to different parts of CA1 and the subiculum.

The dentate gyrus and field CA3 do not receive direct cortical input from regions other than the entorhinal cortex. However, the situation is different for CA1 and the subiculum. Both receive input from entorhinal cortex, but they also receive direct input from the perirhinal and parahippocampal cortices. The perirhinal and parahippocampal cortices do not provide any direct input to the dentate gyrus. The subiculum projects to the entorhinal cortex directly and indirectly through the presubiculum and the parasubiculum. It appears that at least the presubiculum-entorhinal projection is reciprocal, but there is no conclusive evidence for that hypothesis.

Conclusion

Highly processed sensory and sensory associational input terminates in the perirhinal and parahippocampal cortices. Further processing occurs in these regions, and they, in turn, provide the primary cortical input to the entorhinal cortex. Via the perforant pathway, the entorhinal cortex projects mainly to the dentate gyrus of the hippocampal formation. The output structure of the hippocampus, the subiculum, is reciprocally connected with the entorhinal cortex. The subiculum also projects indirectly to the entorhinal cortex through the presubiculum and parasubiculum. Although a primary source of cortical input to the hippocampal formation is from the perirhinal cortex through an entorhinal cortical projection, an important principle of cortico-hippocampal circuitry is that all other parahippocampal regions also project directly to one or more structures in the hippocampal formation. Moreover, all structures within the parahippocampal have extensive cortical and subcortical connections. Thus the connections between the parahippocampal region and the hippocampal formation include multiple parallel and redundant pathways.

See also:GUIDE TO THE ANATOMY OF THE BRAIN: CEREBRAL CORTEX; GUIDE TO THE ANATOMY OF THE BRAIN: HIPPOCAMPUS AND PARAHIPPOCAMPAL REGION

Bibliography

Aggleton, J. P., Vann, S. D., Oswald, C. J., and Good, M. (2000). Identifying cortical inputs to the rat hippocampus that subserve allocentric spatial processes: A simple problem with a complex answer. Hippocampus 10 (4), 466-474.

Amaral, D. G., and Witter, M. P. (1995). Hippocampal formation. In G. Paxinos, ed., The rat nervous system,. 2nd edition. San Diego: Academic Press.

Baleydier, C., and Mauguiere, F. (1985). Anatomical evidence for medial pulvinar connections with the posterior cingulate cortex, the retrosplenial area, and the posterior parahippocampal gyrus in monkeys. Journal of Comparative Neurology 232, 219-228.

Burwell, R. D. (2001). The perirhinal and postrhinal cortices of the rat: Borders and cytoarchitecture. Journal of Comparative Neurology 437, 17-41.

Burwell, R. D., and Amaral, D. G. (1998a). Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices. Journal of Comparative Neurology 398, 179-205.

—— (1998b). The perirhinal and postrhinal cortices of the rat: Interconnectivity and connections with the entorhinal cortex. Journal of Comparative Neurology 391, 293-321.

Insausti, R., Amaral, D. G., and Cowan, M. W. (1987a). The entorhinal cortex of the monkey: II. Cortical afferents. Journal of Comparative Neurology 264, 356-395.

—— (1987b). The entorhinal cortex of the monkey: III. Subcortical afferents. Journal of Comparative Neurology 264, 396-408.

Naber, P. A., Witter, M. P., and Lopez da Silva, F. H. (1999). Perirhinal cortex input to the hippocampus in the rat: Evidence for parallel pathways, both direct and indirect. A combined physiological and anatomical study. European Journal of Neuroscience 11, 4,119-4,133.

—— (2001). Evidence for a direct projection from the postrhinal cortex to the subiculum in the rat. Hippocampus 11, 105-117.

Pikkarainen, M., and Pitkanen, A. (2001). Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the perirhinal and postrhinal cortices in rat. Cerebral Cortex 11, 1,064-1,082.

Saunders, R. C., and Rosene, D. L. (1988). A comparison of the efferents of the amygdala and the hippocampal formation in the rhesus monkey: I. Convergence in the entorhinal, prorhinal, and perirhinal cortices. Journal of Comparative Neurology 271, 153-184.

Shi, C. J., and Cassell, M. D. (1999). Perirhinal cortex projections to the amygdaloid complex and hippocampal formation in the rat. Journal of Comparative Neurology 406, 299-328.

Stefanacci, L., Suzuki, W. A., and Amaral, D. G. (1996). Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys. Journal of Comparative Neurology 375, 552-582.

Suzuki, W. A., and Amaral, D. G. (1990). Cortical inputs to the CA1 field of the monkey hippocampus originate from the perirhinal and parahippocampal cortex but not from area TE. Neuroscience Letters 115, 43-48.

van Groen, T., and Wyss, J. M. (1990). The connections of presubiculum and parasubiculum in the rat. Brain Research 518, 227-243.

van Hoesen, G. W., Rosene, D. L., and Mesulam, M. M. (1979). Subicular input from temporal cortex in the rhesus monkey. Science 205, 608-610.

Witter, M. P., and Amaral, D. G. (1991). Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampas, and subicular complex. Journal of Comparative Neurology 307, 437-459.

Witter, M. P., Groenewegen, H. J., Lopes de Silva, F. H., and Lohman, A. H. M. (1989). Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Progressive Neurobiology 33, 161-253.

Witter, M. P., Naber, P. A., and Lopes da Silva, F. (1999). Perirhinal cortex does not project to the dentate gyrus. Hippocampus 9, 605-606.

Witter, M. P., Naber, P. A., van Haeften, T., Machielsen, W. C., Rombouts, S. A., Barkhof, F., Scheltens, P., and Lopes da Silva, F. H. (2000). Cortico-hippocampal communication by way of parallel parahippocampal-subicular pathways. Hippocampus 10, 398-410.

Rebecca D.Burwell