Information flow through the hippocampus proceeds from dentate gyrus to CA3 to CA1 to the subiculum, with additional input information at each stage and outputs at each of the two final stages. CA2 represents only a very small portion of the hippocampus and its presence is often ignored in accounts of hippocampal function, though it is notable that this small region seems unusually resistant to conditions that usually cause large amounts of cellular damage, such as epilepsy.
The perforant path, which brings information primarily from entorhinal cortex (but also perirhinal cortex, among others), is generally considered the main source of input to the hippocampus. Layer II of entorhinal cortex (EC) brings input to the dentate gyrus and field CA3, while EC layer III brings input to field CA1 and the subiculum. The main output pathways of the hippocampus are the cingulum bundle and the fimbria/fornix, which arise from field CA1 and the subiculum.
Diagram of hippocampus
Perforant path input from EC layer II enters the dentate gyrus and is relayed to region CA3 (and to mossy cells, located in the hilus of the dentate gyrus, which then send information to distant portions of the dentate gyrus where the cycle is repeated). Region CA3 combines this input with signals from EC layer II and sends extensive connections within the region and also sends connections to region CA1 through a set of fibers called the Schaffer collaterals. Region CA1 receives input from the CA3 subfield, EC layer III and the nucleus reuniens of the thalamus (which project only to the terminal apical dendritic tufts in the stratum lacunosum-moleculare). In turn, CA1 projects to the subiculum as well as sending information along the aforementioned output paths of the hippocampus. The subiculum is the final stage in the pathway, combining information from the CA1 projection and EC layer III to also send information along the output pathways of the hippocampus.
The hippocampus also receives a number of subcortical inputs. In Macaca fascicularis, these inputs include the amygdala (specifically the anterior amygdaloid area, the basolateral nucleus, and the periamygdaloid cortex), the medial septum and the diagonal band of Broca, the claustrum, the substantia innominata and the basal nucleus of Meynert, the thalamus (including the anterior nuclear complex, the laterodorsal nucleus, the paraventricular and parataenial nuclei, the nucleus reuniens, and the nucleus centralis medialis), the lateral preoptic and lateral hypothalamic areas, the supramammillary and retromammillary regions, the ventral tegmental area, the tegmental reticular fields, the raphe nuclei (the nucleus centralis superior and the dorsal raphe nucleus), the nucleus reticularis tegementi pontis, the central gray, the dorsal tegmental nucleus, and the locus coeruleus.
It is widely accepted that each of these regions has a unique functional role in the information processing of the hippocampus, but to date the specific contribution of each region is poorly understood.