RRC ID 30912
著者 Okada K, Nishizawa K, Fukabori R, Kai N, Shiota A, Ueda M, Tsutsui Y, Sakata S, Matsushita N, Kobayashi K.
タイトル Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons.
ジャーナル Nat Commun
Abstract Behavioural flexibility is mediated through the neural circuitry linking the prefrontal cortex and basal ganglia. Here we conduct selective elimination of striatal cholinergic interneurons in transgenic rats by immunotoxin-mediated cell targeting. Elimination of cholinergic interneurons from the dorsomedial striatum (DMS), but not from the dorsolateral striatum, results in enhanced reversal and extinction learning, sparing the acquisition of place discrimination. This enhancement is prevented by infusion of a non-selective muscarinic acetylcholine receptor agonist into the DMS either in the acquisition, reversal or extinction phase. In addition, gene-specific silencing of M4 muscarinic receptor by lentiviral expression of short hairpin RNA (shRNA) mimics the place reversal learning promoted by cholinergic elimination, whereas shRNA-mediated gene silencing of M1 muscarinic receptor shows the normal performance of reversal learning. Our data indicate that DMS cholinergic interneurons inhibit behavioural flexibility, mainly through the M4 muscarinic receptor, suggesting that this role is engaged to the stabilization of acquired reward contingency and the suppression of response switch to changed contingency.
巻・号 5
ページ 3778
公開日 2014-5-6
DOI 10.1038/ncomms4778
PII ncomms4778
PMID 24797209
MeSH Animals Conditioning, Classical* Corpus Striatum / cytology* Discrimination Learning* Gene Knockdown Techniques Interneurons / cytology* Locomotion Rats Rats, Transgenic Receptors, Muscarinic / genetics Receptors, Muscarinic / metabolism*
IF 12.121
引用数 32
WOS 分野 NEUROSCIENCES
リソース情報
遺伝子材料 CS-CA-MCS (RDB05963)