TY - JOUR
T1 - Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation
AU - Tsutsui-Kimura, Iku
AU - Takiue, Hiroyuki
AU - Yoshida, Keitaro
AU - Xu, Ming
AU - Yano, Ryutaro
AU - Ohta, Hiroyuki
AU - Nishida, Hiroshi
AU - Bouchekioua, Youcef
AU - Okano, Hideyuki
AU - Uchigashima, Motokazu
AU - Watanabe, Masahiko
AU - Takata, Norio
AU - Drew, Michael R.
AU - Sano, Hiromi
AU - Mimura, Masaru
AU - Tanaka, Kenji F.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms14304
DO - 10.1038/ncomms14304
M3 - Article
C2 - 28145402
AN - SCOPUS:85011554705
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
M1 - 14304
ER -