2019 Fiscal Year Annual Research Report
Multiscale analyses of dynamic states in the schizophrenic brain
Publicly Offered Research
| Project Area | Constructive understanding of multi-scale dynamism of neuropsychiatric disorders |
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| Project/Area Number |
19H05233
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
McHugh Thomas 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (50553731)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | hippocampus / oscillations / medial septum / memory / theta / ripple / actylcholine |
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| Outline of Annual Research Achievements |
During the past fiscal year we have made substantial progress in characterizing the novel excitatory projection from the CA2 region of the hippocampus to the medial septum (MS). With the assistance of the Johansen lab we have employed various viral tracing methods to map the inputs/outputs of the circuit, demonstrating roughly 10% of CA2 pyramidal cells (PCs) project to PV+ interneurons in the MS. This subset of PCs has unique genetic and anatomical profiles as determined by RNAscope and projection specific rabies tracing. Further, in collaboration with Li lab from Peking University, we have established in vivo fluorescent monitoring of acetylcholine levels, combining fiber phototometry and GRAB sensors. Preliminary data suggest activation of the CA2-MS circuit decrease choline, weakens theta oscillations and impairs memory and social behaviors; all endophenotypes related to schizophrenia. Related to this we are collaborating with the Johansen lab on their project to use similar techniques and sensors to monitor NE levels. Through these efforts we have generated new viral variants and approaches, both AAV and rabies based, that we will share with other members of the Multiscale group.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Anatomical and neurochemical characterization of the circuit has gone extremely well. We also collected substantial behavioral data using optogenetic manipulation of this pathway that demonstrates clear phenotypes in memory and alteration in social behaviors; all in line with our plans for this fiscal year.
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| Strategy for Future Research Activity |
During the next fiscal year the focus will be on in vivo physiological experiments. We have established a viral-based method to specifically tag CA2 neurons projecting to the medial septum with ChR2 and can optically identify this subpopulation via laser application. We will characterize their activity in freely behaving mice during memory encoding, consolidation and recall and look for evidence of patterns that correlate with changes in acetylcholine and with hippocampal oscillation patterns. We will establish simultaneous optical and physiological recordings to measure oscillations and acetylcholine dynamics in a single preparation.
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[Journal Article] Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection2019
Author(s)
Adaikkan Chinnakkaruppan, Middleton Steven J, Marco Asaf, Pao Ping-Chieh, Mathys Hansruedi, Kim David Nam-Woo, Gao Fan, Young Jennie Z, Suk Ho-Jun, Boyden Edward S, McHugh Thomas J, Tsai Li-Huei
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Journal Title
Neuron
Volume: 102
Pages: 929~943
DOI
Peer Reviewed / Int'l Joint Research
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