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

Keigo Kohara, Michele Pignatelli, Alexander J. Rivest, Hae Yoon Jung, Takashi Kitamura, Junghyup Suh, Dominic Frank, Koichiro Kajikawa, Nathan Mise, Yuichi Obata, Ian R. Wickersham, Susumu Tonegawa

Research output: Contribution to journalArticlepeer-review

226 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)269-279
Number of pages11
JournalNature neuroscience
Volume17
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits'. Together they form a unique fingerprint.

Cite this