title: Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.
abstract: The dorsal and ventral hippocampal regions (dHP and vHP) are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP) and multi unit activities (MUA) upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2). Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD) fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP), which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS) were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
authors: Norio
authors: N
authors: Takata
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors: Keitaro
authors: K
authors: Yoshida
authors: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
authors: Yuji
authors: Y
authors: Komaki
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors: Ming
authors: M
authors: Xu
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan; Department of Psychiatry, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Sakai
authors: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan; Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
authors: Keigo
authors: K
authors: Hikishima
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors: Masaru
authors: M
authors: Mimura
authors: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors: Hideyuki
authors: H
authors: Okano
authors: Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors: Kenji F
authors: KF
authors: Tanaka
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D020007:Implants, Experimental; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008822:Mice, Transgenic; D055100:Optical Fibers; D062308:Optogenetics / Q000379:methods*; D010100:Oxygen / Q000097:blood; D017966:Pyramidal Cells / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins; D010100:Oxygen