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Behavior control by manipulating neurocircuit using optogenetics and/or chemicogenetics

開催日 2014/9/12
時間 17:10 - 19:10
会場 Room B(501)
Chairperson(s) 成塚 裕美 / Hiromi Naritsuka (東京大学大学院 医学系研究科 細胞分子生理学教室 / Department of Physiology, Graduate School of Medicine, University of Tokyo, Japan)
山中 章弘 / Akihiro Yamanaka (名古屋大学環境医学研究所 / Research Institute of Environmental Medicine, Nagoya University, Japan)

Novel circuits for stress coping

  • S2-B-3-5
  • Jaideep Bains:1 Tamas Fuzesi:1 Wataru Inoue:1 Jaclyn Cusulin:1 
  • 1:Hotchkiss Brian Institute, University of Calgary, Calgary, Canada 

The response to stress is coordinated by neurons in the paraventricular nucleus of the hypothalamus that manufacture and secrete the neuropeptide, corticotropin releasing hormone (CRH). These cells parse synaptic signals funneled to them by projection neurons as well as a local network of GABA interneurons and use this information to launch an immediate and appropriate response to stress. While viewed largely as the principal regulators of the endocrine response to stress, anatomical studies on PVN projections also hint at a broader role for this nucleus in regulating distinct behaviors through direct synaptic inputs to other brain regions. The role of putative neural circuits from PVN CRH neurons has never been investigated. To assess the non-endocrine functions of PVN CRH neurons specifically, we utilized optogenetic tools in a recently developed Crh-IRES-Cre Ai14 tdTomato mouse line. By combining Channel Rhodopsin Assisted Circuit Mapping with electrophysiology we show that in vivo activation of PVN CRH neurons increases c-Fos expression in ipsilateral lateral hypothalamus (LH) and lateral septum (LS). Using anatomical tracing methods and in vitro electrophysiology, we demonstrate that PVN-CRH neurons send a direct glutamatergic projection to LH neurons in the lateral hypothalamus. In vivo optogenetic stimulation of this projection resulted in immediate and robust grooming behavior. Similar behavior was observed immediately following exposure of animals to a mild foot-shock, indicating that it may be part of a stress-coping strategy. To test whether PVN-CRH neurons were necessary for stress-induced grooming, we optogenetically silenced these cells in vivo immediately following stress. This manipulation reduced grooming behavior. We conclude that this novel circuit, originating from CRH neurons in the PVN is necessary for active coping behavior that follows exposure to an acute stress.

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