CA2: A Highly Connected Intrahippocampal Relay

Annu Rev Neurosci. 2020 Jul 8;43:55-72. doi: 10.1146/annurev-neuro-080719-100343. Epub 2019 Dec 24.


Although Lorente de No' recognized the anatomical distinction of the hippocampal Cornu Ammonis (CA) 2 region, it had, until recently, been assigned no unique function. Its location between the key players of the circuit, CA3 and CA1, which along with the entorhinal cortex and dentate gyrus compose the classic trisynaptic circuit, further distracted research interest. However, the connectivity of CA2 pyramidal cells, together with unique patterns of gene expression, hints at a much larger contribution to hippocampal information processing than has been ascribed. Here we review recent advances that have identified new roles for CA2 in hippocampal centric processing, together with specialized functions in social memory and, potentially, as a broadcaster of novelty. These new data, together with CA2's role in disease, justify a closer look at how this small region exerts its influence and how it might best be exploited to understand and treat disease-related circuit dysfunctions.

Keywords: disease; hippocampus; memory; novelty; replay; spatial coding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CA2 Region, Hippocampal / physiology*
  • Entorhinal Cortex / physiology
  • Hippocampus / physiology*
  • Humans
  • Memory / physiology*
  • Nerve Net / physiology
  • Neural Pathways / physiology*