Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits

Nat Neurosci. 2014 Feb;17(2):269-79. doi: 10.1038/nn.3614. Epub 2013 Dec 15.

Abstract

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA2 Region, Hippocampal / cytology*
  • Entorhinal Cortex / cytology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Potentials / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Nerve Fibers / physiology
  • Nerve Net / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / physiology*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Optogenetics*
  • Patch-Clamp Techniques
  • Photic Stimulation
  • RGS Proteins / genetics
  • RGS Proteins / metabolism

Substances

  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RGS Proteins
  • Rgs1 protein, mouse