Format

Send to

Choose Destination
Neuron. 2017 May 3;94(3):642-655.e9. doi: 10.1016/j.neuron.2017.04.014.

Chronic Loss of CA2 Transmission Leads to Hippocampal Hyperexcitability.

Author information

1
Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wakoshi, Saitama 351-0198, Japan.
2
Team of Synaptic Plasticity and Neural Networks, Center of Psychiatry and Neuroscience, Inserm U894, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
3
Laboratory for Circuit and Behavioral Physiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wakoshi, Saitama 351-0198, Japan; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan. Electronic address: tjmchugh@brain.riken.jp.

Abstract

Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility and generating ripple oscillations, an interventional examination of the integrative functions of these connections has yet to be reported. Here we demonstrate that CA2 recruits feedforward inhibition in CA3 and that chronic genetically engineered shutdown of CA2-pyramidal-cell synaptic transmission consequently results in increased excitability of the recurrent CA3 network. In behaving mice, this led to spatially triggered episodes of network-wide hyperexcitability during exploration accompanied by the emergence of high-frequency discharges during rest. These findings reveal CA2 as a regulator of network processing in hippocampus and suggest that CA2-mediated inhibition in CA3 plays a key role in establishing the dynamic excitatory and inhibitory balance required for proper network function.

KEYWORDS:

CA2; CA3; DREADD; hippocampus; place cell; ripple; spatial coding; tetanus toxin; theta oscillation

PMID:
28472661
DOI:
10.1016/j.neuron.2017.04.014
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center