Major Afferent and Efferent Projections to the Hippocampus

By Mark Yarchoan

The primary afferent to the hippocampus is the perforant pathway. This pathway begins

in the layer II and III neurons of the entorhinal cortex, and synapses amongst the granular cells of

the dentate gyrus, one of two major structures in the hippocampus (Bear 791-2). Terminal

degeneration studies have found that most of the synapses of the perforant path in the dentate

gyrus arise from perforant axons that begin from the ipsilateral entorhinal cortex. Perforant

fibers which begin in the lateral parts of the entorhinal cortex generally project to the outer layers

of the dentate gyrus, whereas fibers which begin in the median parts of the entorhinal cortex

terminate in deeper regions of the dentate gyrus (Baudry 46-7). Other afferent fibers arise from

the cingulate gyrus (part of a hippocampus circuit described below), the controlateral

hippocampus, and the medial septal nucleus (Arslan 329).

The dentate gyrus projects to mossy cells in the hilus of the dentate gyrus, the statum

lucidum, and most significantly to the CA3 region of the Ammon’s horn. The axons which

project from the dentate gyrus to the CA3 are called mossy fibers. The CA3 neurons in turn

project to the CA1, another region of the Ammon’s horn of the hippocampus, by way of the

Shaffer collateral (Bear 791). The CA1 projects back to deep layers of the entorhinal cortex,

thereby completing a circuit – entorhinal cortex to dentate gyrus to CA3 to CA1. A degeneration

of the perforant pathway within this circuit is believed to underlie Alzheimer’s disease. The

entorhinal cortex also projects directly back to CA1 through Alvear fibers (Baudry 46-7).

In addition to projecting to the CA1, the CA3 neurons also project out of the

hippocampus via the fornix and anterior commissure to parts of the frontal cortex, the thalamus,

and the hypothalamus, particularly the mammillary bodies. The mammilary bodies project to the

anterior nucleus of the thalamus, which projects to the cingulate gyrus. The cingulate gyrus
projects back to the dentate gyrus, forming another complete circuit that can provide positive or

negative feedback to the hippocampus (Arslan 327 -330).

Review of Primary Hippocampal Circuits:

1) Entorhinal cortex  dentate gyrus  CA3  CA1  entorhinal cortex

2) Dentate gyrus  CA3  mammilary bodies  anterior nucleus of the thalamus  cingulate

gyrus  dentate gyrus

Works Cited

Arslan, Orhan. Neuroanatomical Basis of Clinical Neurology. Cambridge: MIT Press, 1993.

Baudry, Michel, Joel L. Davis, and Richard F. Thompson. Synaptic Plasticity: Molecular,

Cellular, and Functional Aspects. New York: Parthenon Publishing Group, 2001.

Bear, Mark F., Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain -

2nd ed. Baltimore: Lippincott Williams & Wilkins, 2001.