Hippocampus Anatomy - Basic Hippocampal Circuit

Basic Hippocampal Circuit

Starting at the dentate gyrus and working inward along the S-curve of the hippocampus means traversing a series of narrow zones. The first of these, the dentate gyrus (DG), is actually a separate structure, a tightly packed layer of small granule cells wrapped around the end of the hippocampus proper, forming a pointed wedge in some cross-sections, a semicircle in others. Next come a series of Cornu Ammonis areas: first CA4 (which underlies the dentate gyrus), then CA3, then a very small zone called CA2, then CA1. The CA areas are all filled with densely packed pyramidal cells similar to those found in the neocortex. After CA1 comes an area called the subiculum. After this comes a pair of ill-defined areas called the presubiculum and parasubiculum, then a transition to the cortex proper (mostly the entorhinal area of the cortex). Most anatomists use the term "hippocampus proper" to refer to the four CA fields, and "hippocampal formation" to refer to the hippocampus proper plus dentate gyrus and subiculum.

The major pathways of signal flow through the hippocampus combine to form a loop. Most external input comes from the adjoining entorhinal cortex, via the axons of the so-called perforant path. These axons arise from layer 2 of the entorhinal cortex (EC), and terminate in the dentate gyrus and CA3. There is also a distinct pathway from layer 3 of the EC directly to CA1. Granule cells of the DG send their axons (called "mossy fibers") to CA3. Pyramidal cells of CA3 send their axons to CA1. Pyramidal cells of CA1 send their axons to the subiculum and deep layers of the EC. Subicular neurons send their axons mainly to the EC. The perforant path-to-dentate gyrus-to-CA3-to-CA1 was called the trisynaptic circuit by Per Andersen, who noted that thin slices could be cut out of the hippocampus perpendicular to its long axis, in a way that preserves all of these connections. This observation was the basis of his lamellar hypothesis, which proposed that the hippocampus can be thought of as a series of parallel strips, operating in a functionally independent way. The lamellar concept is still sometimes considered to be a useful organizing principle, but more recent data, showing extensive longitudinal connections within the hippocampal system, have required it to be substantially modified.

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. The hippocampus also receives direct monosynaptic projections from the cerebellar fastigial nucleus.