Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition From Habitual to Goal-Directed Reward-Seeking Behavior.
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
15 11 2020
15 11 2020
Historique:
received:
06
01
2020
revised:
22
04
2020
accepted:
22
04
2020
pubmed:
23
6
2020
medline:
9
3
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift. To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors. The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition. Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior.
Sections du résumé
BACKGROUND
Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift.
METHODS
To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors.
RESULTS
The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition.
CONCLUSIONS
Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior.
Identifiants
pubmed: 32564901
pii: S0006-3223(20)31549-3
doi: 10.1016/j.biopsych.2020.04.023
pmc: PMC7584758
mid: NIHMS1591448
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
797-808Subventions
Organisme : NIAAA NIH HHS
ID : K01 AA027773
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA018779
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088260
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK100469
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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