Hypothalamic control of hippocampal action selection

2017 Fiscal Year Annual Research Report

• Project Area: Mechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
• Project/Area Number: 17H05591
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: McHugh Thomas 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (50553731)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: supramammillary nucleus / hippocampus / social behavior / spatial behavior / optogenetics

Outline of Annual Research Achievements

During the last fiscal year we have completed the majority of work proposed, including anatomical and immediate-early gene activation characterization of the circuit and electrophysiological recordings. The first manuscript reporting these findings is nearly completed and will be submitted within the coming months. In it we report that we have found that the anatomically and physiologically distinct parallel projections from the supramammillary nucleus (SuM) of the hypothalamus to the CA2 and dentate gyrus (DG) hippocampal regions differentially modulate cognition in a task specific manner. Employing immediate-early gene expression labeling, optogenetics and in vivo recordings in a newly developed SuM-Cre transgenic mouse line we find that the SuM to DG circuit is preferentially engaged by spatial novelty while the neurons targeting CA2 are activated by social novelty. As a result, photoinhibition of the SuM-DG projections leads to deficits in recognizing contextual change while photostimulation of the SuM-CA2 circuit impairs the expression of social memory. These data demonstrate that the hypothalamus can play a task-specific role in the encoding and expression of hippocampal memory.

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

The work has gone very smoothly and several manuscripts are in preparation, including one to be submitted shortly. In addition the support of this grant to the project helped fund a paper published in Science in January 2018.

Strategy for Future Research Activity

In the coming year we will extend our studies of the SuM to examine the role of the SuM to medial septum in the regulation of theta oscillations and the performance of spatial working memory tasks.

Research Products

• [Journal Article] Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics (2018)
  • Author(s): Shuo Chen, Adam Z. Weitemier, Xiao Zeng, Linmeng He, Xiyu Wang, Yanqiu Tao, Arthur J.Y. Huang, Yuki Hashimotodani, Masanobu Kano, Hirohide Iwasaki, Laxmi Kumar Parajuli, Shigeo Okabe, Daniel B. Loong Teh, Angelo H. All, Iku Tsutsui-Kimura, Kenji F. Tanaka, Xiaogang Liu, Thomas. J. McHugh
  • Journal Title: Science Volume: 359 Pages: 679-684
  • DOI: 10.1126/science.aaq1144
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Divergent Information Routing by a Hypothalamo-Hippocampal Circuit During Spatial and Social Memory (2017)
  • Author(s): Linmeng He, Shuo Chen, Marie E. Wintzer, Yanqiu Tao, Hiroshi Hama, Kana Namiki, Atsushi Miyawaki, Roman Boehringer, Denis Polygalov, Arthur J.Y. Huang, Thomas J. McHugh
  • Organizer: Japan Neuroscience Society
  • Int'l Joint Research