Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-02-01

AUTHORS

Iku Tsutsui-Kimura, Hiroyuki Takiue, Keitaro Yoshida, Ming Xu, Ryutaro Yano, Hiroyuki Ohta, Hiroshi Nishida, Youcef Bouchekioua, Hideyuki Okano, Motokazu Uchigashima, Masahiko Watanabe, Norio Takata, Michael R Drew, Hiromi Sano, Masaru Mimura, Kenji F Tanaka

ABSTRACT

Impaired motivation is present in a variety of neurological disorders, suggesting that decreased motivation is caused by broad dysfunction of the nervous system across a variety of circuits. Based on evidence that impaired motivation is a major symptom in the early stages of Huntington's disease, when dopamine receptor type 2-expressing striatal medium spiny neurons (D2-MSNs) are particularly affected, we hypothesize that degeneration of these neurons would be a key node regulating motivational status. Using a progressive, time-controllable, diphtheria toxin-mediated cell ablation/dysfunction technique, we find that loss-of-function of D2-MSNs within ventrolateral striatum (VLS) is sufficient to reduce goal-directed behaviours without impairing reward preference or spontaneous behaviour. Moreover, optogenetic inhibition and ablation of VLS D2-MSNs causes, respectively, transient and chronic reductions of goal-directed behaviours. Our data demonstrate that the circuitry containing VLS D2-MSNs control motivated behaviours and that VLS D2-MSN loss-of-function is a possible cause of motivation deficits in neurodegenerative diseases. More... »

PAGES

14304

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms14304

DOI

http://dx.doi.org/10.1038/ncomms14304

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083400764

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28145402


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