RRC ID 30912
Author Okada K, Nishizawa K, Fukabori R, Kai N, Shiota A, Ueda M, Tsutsui Y, Sakata S, Matsushita N, Kobayashi K.
Title Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons.
Journal 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.
Volume 5
Pages 3778
Published 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
Times Cited 32
DNA material CS-CA-MCS (RDB05963)