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Mayo Clinic

Biol. Psychiatry, Published online: May 06, 2020 | https://doi.org/10.1016/j.biopsych.2020.04.023 Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition from Habitual to Goal-Directed Reward-Seeking Behavior

Seungwoo Kang^1,5, Sa-Ik Hong^1,5, Jeyeon Lee^2,3, Lee Peyton¹, Matthew Baker¹, Sun Choi¹, Hyunjung Kim¹, Su-Youne Chang², Doo-Sup Choi^1,4,*

¹Department of Molecular Pharmacology and Experimental Therapeutics, ²Department of Neurologic Surgery, ³Department of Radiology, ⁴Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN

⁵These authors contributed to this article equally

^*Corresponding author

Abstract

Background
Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of 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 impact 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 designer receptors exclusively activated by designer drugs (DREADDs). 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 (dMSNs and iMSNs). To evaluate the behavioral consequences, we trained mice in nose-poke 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 (sEPSCs) in the dMSNs, whereas it increased the amplitude of the sEPSCs and decreased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in the iMSNs. 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 the MSNs’ activity and facilitates shifting from habitual to goal-directed reward-seeking behavior.

논문정보

형식Research article
게재일2020년 05월 (BRIC 등록일 2020-05-11)
연구진국외 연구진
분야

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