TY - JOUR
T1 - Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition From Habitual to Goal-Directed Reward-Seeking Behavior
AU - Kang, Seungwoo
AU - Hong, Sa Ik
AU - Lee, Jeyeon
AU - Peyton, Lee
AU - Baker, Matthew
AU - Choi, Sun
AU - Kim, Hyunjung
AU - Chang, Su Youne
AU - Choi, Doo Sup
N1 - Publisher Copyright:
© 2020 Society of Biological Psychiatry
PY - 2020/11/15
Y1 - 2020/11/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.biopsych.2020.04.023
DO - 10.1016/j.biopsych.2020.04.023
M3 - Article
C2 - 32564901
AN - SCOPUS:85086516011
SN - 0006-3223
VL - 88
SP - 797
EP - 808
JO - Biological psychiatry
JF - Biological psychiatry
IS - 10
ER -