Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice

• Published in: PloS one Vol. 10; no. 6; p. e0130163
• Main Authors: Sakaguchi, Masanori, Kim, Karam, Yu, Lily Mae Yee, Hashikawa, Yoshiko, Sekine, Yukiko, Okumura, Yuki, Kawano, Masako, Hayashi, Masanobu, Kumar, Deependra, Boyden, Edward S, McHugh, Thomas J, Hayashi, Yasunori
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.06.2015; Public Library of Science (PLoS)
• Subjects: Animals; Brain; Brain research; CA1 Region, Hippocampal - physiology; Circuits; Fear; Fear - physiology; Female; Gene expression; Genetic engineering; Hippocampus; In Situ Hybridization; Laboratories; Light; Male; Medicine; Memory; Memory - physiology; Mental Recall - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurons - cytology; Neurons - physiology; Neurosciences; Opsins; Optics; Optogenetics - methods; Proteins - metabolism; Proton Pumps - metabolism; Pyramidal cells; Recall; Rodents; Science; Sleep; Transgenic animals; Transgenic mice; New York; United States > US; Massachusetts; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130163

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.