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Control of neural circuit function by the endocannabinoid 2-arachidonoylglycerol

開催日 2014/9/12
時間 15:00 - 17:00
会場 Room F(302)
Chairperson(s) 狩野 方伸 / Masanobu Kano (東京大学大学院医学系研究科 神経生理学分野 / Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Japan)
渡辺 雅彦 / Masahiko Watanabe (北海道大学大学院医学研究科 解剖学講座 解剖発生学分野 / Department of Anatomy, Hokkaido University Graduate School of Medicine, Japan)

Cannabinoid-dependent reorganization of neuronal projection in the developing barrel cortex

  • S2-F-2-4
  • 木村 文隆 / Fumitaka Kimura:1 伊丹 千晶 / Chiaki Itami:2 Huang J-E / J-E Huang:3 山崎 美和子 / Miwako Yamasaki:4 渡辺 雅彦 / Masahiko Watanabe:4 Lu H-C / H-C Lu:3 
  • 1:大阪大院医分子神経科学 / Osaka Univ.Grad.Sch.of Med., Japan 2:埼玉医科大・医・生理 / Dept Physiol, Saitama Med Univ, Saitama, Japan 3:Dept Pediatrics, Baylor Coll Med, Houston, USA / Dept Pediatrics, Baylor Coll Med, Houston, USA 4:北海道大院医解剖発生 / Dept Anatomy, Hokkaido Univ, Hokkaido, Japan 

Cannabinoids have involved with human lives from prehistoric age, but how it affects neuronal circuit formation is not well understood. Here, we show cannabinoid signaling plays a major role in the formation of thalamocortical projection, and its disturbance causes a disruption of neural network. We showed previously that spike timing-dependent depression (tLTD) at L4-L2/3 synapse, which requires cannabinoid signaling, appears only after the initiation of critical period of map plasticity, or P12-13, and this synapse exhibits only LTP in a timing-dependent manner (tLTP) before P12 in the rodent barrel cortex. We found that thalamic terminals to L2/3 express cannabinoid receptors (CB1R), and these synapses exhibit only tLTD, exactly opposite to L4-L2/3 synapses before P12. Global and cortical excitatory cell-specific knockouts for CB1R supported this finding. Thalamus activates not only L2/3 but also L4, thus convergence of opposite spike timing-dependent plasticity (STDP) to L2/3 creates a situation, where thalamic activity strengthens L4 to L2/3 synapses by tLTP, at the same time weakens its aberrant projection to L2/3 through tLTD. Electrophysiological study confirmed such self-organizing, bidirectional alteration of synaptic strength. Thalamus to L4 synapses lack CB1R, nor STDP, either. Thus, thalamic activity could reorganize the cortical network by interaction of two STDPs without changing innervation to L4. Consistent with this, thalamocortical projections retracted strongly by exogenous administration of CB1R agonists, including 9-tetrahydrocannabinol (THC, active component of marijuana). Similarly, CB1R mutants exhibits completely distracted thalamocortical innervation. These findings indicate that age and location specific activation of CB1R plays an important role in shaping the cortical network, and abuse of these chemicals would result in a disruption of neural network.

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