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Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice
Authors:Masanori Sakaguchi  Karam Kim  Lily Mae Yee Yu  Yoshiko Hashikawa  Yukiko Sekine  Yuki Okumura  Masako Kawano  Masanobu Hayashi  Deependra Kumar  Edward S. Boyden  Thomas J. McHugh  Yasunori Hayashi
Affiliation:1. Brain Science Institute, RIKEN, Wako, Saitama, Japan.; 2. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.; 3. The MIT Media Laboratory, Synthetic Neurobiology Group, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.; 4. Saitama University Brain Science Institute, Saitama University, Saitama, Japan.; Nathan Kline Institute and New York University Langone Medical Center, UNITED STATES,
Abstract:The optogenetic manipulation of light-activated ion-channels/pumps (i.e., opsins) can reversibly activate or suppress neuronal activity with precise temporal control. Therefore, optogenetic techniques hold great potential to establish causal relationships between specific neuronal circuits and their function in freely moving animals. Due to the critical role of the hippocampal CA1 region in memory function, we explored the possibility of targeting an inhibitory opsin, ArchT, to CA1 pyramidal neurons in mice. We established a transgenic mouse line in which tetracycline trans-activator induces ArchT expression. By crossing this line with a CaMKIIα-tTA transgenic line, the delivery of light via an implanted optrode inhibits the activity of excitatory CA1 neurons. We found that light delivery to the hippocampus inhibited the recall of a contextual fear memory. Our results demonstrate that this optogenetic mouse line can be used to investigate the neuronal circuits underlying behavior.
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