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Working Memory and Executive Function

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Behavioral flexibility is inhibited by cholinergic interneurons in the dorsomedial striatum, via muscarinic M4 receptors

  • P2-263
  • 岡田 佳奈 / Kana Okada:1 西澤 佳代 / Kayo Nishizawa:2 深堀 良二 / Ryoji Fukabori:2 甲斐 信行 / Nobuyuki Kai:2 塩田 明 / Akira Shiota:3 上田 正次 / Masatsugu Ueda:3 筒井 雄二 / Yuji Tsutsui:4 坂田 省吾 / Shogo Sakata:1 松下 夏樹 / Natsuki Matsushita:5 小林 和人 / Kazuto Kobayashi:2,6 
  • 1:広島大院・総合科学・行動科学 / Dept Behav Sci, Grad Sch Integr Arts & Sci, Hiroshima Univ, Hiroshima, Japan 2:福島県立医大・医・生体機能 / Dept Mol Genet, Fukushima Med Univ, Fukushima, Japan 3:特殊免疫研究所(株) / Inst Immunol, Co, Ltd, Tokyo, Japan 4:福島大院・共生理工・人間支援 / Dept Hum Support Syst, Fukushima Univ, Fukushima, Japan 5:愛媛大・医附属病院・先端医療創生 / Transl Res Ctr, Ehime Univ Hosp, Ehime, Japan 6:JST・CREST / JST, CREST, Tokyo, Japan 

The neural mechanisms underlying behavioral flexibility are linked to the prefrontal cortex-basal ganglia circuit. Particularly, the flexibility is mediated through the dorsomedial striatum (DMS). To address the role of cholinergic interneurons in the DMS in behavioral flexibility, we conducted the selective elimination of cholinergic interneurons in rats by the immunotoxin-mediated cell targeting. Elimination of cholinergic interneurons in the DMS, but in dorsolateral striatum, resulted in the amelioration of reversal/extinction learning, sparing the acquisition of original place learning. This enhancement was reversed by the infusion of non-selective muscarinic receptor agonist into the DMS, either during the acquisition or reversal/extinction learning. Furthermore, the gene silencing of M1 or M4 muscarinic receptor in the DMS was conducted by lentiviral expression of short hairpin RNA. M4 receptor knockdown mimicked the enhancement of reversal learning shown by the cholinergic elimination, but M1 receptor knockdown did not. Our data provide the evidence that the cholinergic interneurons in the DMS are involved in the inhibition of behavioral flexibility, mainly through the M4 muscarinic receptor.

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