title: Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice.
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.
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Karam
authors.initials: K
authors.lastname: Kim
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Lily Mae Yee
authors.initials: LM
authors.lastname: Yu
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashikawa
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okumura
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kawano
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
authors.forename: Deependra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: The MIT Media Laboratory, Synthetic Neurobiology Group, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McHugh
authors.affiliation: Brain Science Institute, RIKEN, Wako, Saitama, Japan; Saitama University Brain Science Institute, Saitama University, Saitama, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D062308:Optogenetics / Q000379:methods; D011506:Proteins / Q000378:metabolism; D017494:Proton Pumps / Q000378:metabolism*
chemical_list: C529569:CAMK2N1 protein, human; D011506:Proteins; D017494:Proton Pumps