Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity.
The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca2+indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca2+elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior.SIGNIFICANCE STATEMENTAn opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has been questioned by recent reports. In the present study, we measured concurrent Ca2+activity patterns of D1- and D2-MSNs in the ventrolateral striatum during food-incentive, goal-directed behavior in mice. According to Ca2+activity patterns, we conducted timing-specific optogenetic inhibition of each type of MSN. We demonstrated that both D1- and D2-MSNs in the ventrolateral striatum commonly and positively encoded action initiation, whereas only D1-MSNs positively encoded sustained motivated behavior. These findings led us to reconsider the prevailing notion of a functional segregation of MSN activity in the ventral striatum.
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.|Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Akiyo
A
Natsubori
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Iku
I
Tsutsui-Kimura
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Hiroshi
H
Nishida
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Youcef
Y
Bouchekioua
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Hiroshi
H
Sekiya
Department of Anatomy, University of Hokkaido Graduate School of Medicine, Sapporo 060-8638 Japan, and.
Motokazu
M
Uchigashima
Department of Anatomy, University of Hokkaido Graduate School of Medicine, Sapporo 060-8638 Japan, and.
Masahiko
0000-0001-5037-7138
M
Watanabe
Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium.
Alban
0000-0002-0682-5877
A
de Kerchove d'Exaerde
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Masaru
M
Mimura
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Norio
N
Takata
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan, kftanaka@keio.jp.
Kenji F
0000-0003-2511-0057
KF
Tanaka
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D030141:Feedback, Psychological / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011954:Receptors, Dopamine / Q000378:metabolism*; D012201:Reward
D011954:Receptors, Dopamine
fiberphotometry; food-incentive goal-directed behavior; motivation; optogenetic inhibition; ventrolateral striatum; yellow cameleon