CA2 Disinhibition and Schizophrenic Phenotypes

2013 Fiscal Year Annual Research Report

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 25116529
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: MCHUGH Thomas 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (50553731)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 海馬 hippocampus / トランスジェニックマウス / 統合失調症 schizophrenia / アデノ随伴ウィルス

Research Abstract

During the FY2013 we have achieved several major milestones:
(1) We have achieved highly reproducible strong expression of the ClCtx peptide specifically in CA2 via viral infection of the CACNG5-cre line. The primary improvement we made to earlier attempts was to adopt the AVV-DJ/8 serotype as our primary viral vector. We have perfected in-house high-titer production of this virus and this has allowed highly reproducible experiments.
(2) We have conducted in vivo physiological recordings in the hippocampi of mice infected with the ClCtx virus; analyses of these data is ongoing.
(3) We have started behavioral experiment on ClCtx expressing mice with a focus on the impact of disinhibition on contextual exploration and social behavior.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

The in vitro portion of the project, namely testing the effectiveness of the ClCtx in hippocampal slice, has progressed slower than planned. The primary reason is the access to the appropriate equipment, namely an invitro recording setup with whole cell patch capabilities, has been difficult to obtain, however through internal collaboration we hope to resolve this issue shortly.

Strategy for Future Research Activity

This ongoing work was presented at the マイクロ精神病態 meeting in Nagoya in September, 2013. This meeting provided an excellent opportunity to share our progress and receive valuable and insightful comments from colleagues.
In the coming fiscal year the primary goal of these experiments will be to complete the behavioral and in vivo physiological characterization of the CA2-Chlorotoxin expressing mouse. Recent publications have indicated that silencing CA2 output via tentanus toxin expression leads to social memory deficits. We anticipate that our manipulation, which should increase CA2 output, may have a similar phenotype. The aim of our behavioral experiments are to assess social interaction, social memory and social habituation. The in vivo recordings will be focused on confirming the physiological impact of the toxin expression.