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

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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 1 2014

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Optogenetics
Hippocampal CA2 Region
Learning
Entorhinal Cortex
Episodic Memory
Pyramidal Cells
Dentate Gyrus
Automatic Data Processing
Transgenic Mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kohara, K., Pignatelli, M., Rivest, A. J., Jung, H. Y., Kitamura, T., Suh, J., ... Tonegawa, S. (2014). Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits. Nature Neuroscience, 17(2), 269-279. https://doi.org/10.1038/nn.3614

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits. / Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J.; Jung, Hae Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R.; Tonegawa, Susumu.

In: Nature Neuroscience, Vol. 17, No. 2, 01.02.2014, p. 269-279.

Research output: Contribution to journalArticle

Kohara, K, Pignatelli, M, Rivest, AJ, Jung, HY, Kitamura, T, Suh, J, Frank, D, Kajikawa, K, Mise, N, Obata, Y, Wickersham, IR & Tonegawa, S 2014, 'Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits', Nature Neuroscience, vol. 17, no. 2, pp. 269-279. https://doi.org/10.1038/nn.3614
Kohara, Keigo ; Pignatelli, Michele ; Rivest, Alexander J. ; Jung, Hae Yoon ; Kitamura, Takashi ; Suh, Junghyup ; Frank, Dominic ; Kajikawa, Koichiro ; Mise, Nathan ; Obata, Yuichi ; Wickersham, Ian R. ; Tonegawa, Susumu. / Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits. In: Nature Neuroscience. 2014 ; Vol. 17, No. 2. pp. 269-279.
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