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.