Astrocytic Regulation of Basal Ganglia Dopamine/D2-Dependent Behaviors

Abstract

Astrocytic involvement in dopamine dynamics related to motivational and sensorimotor gating abilities is unknown. We found that dysbindin-1 (Dys1) hypofunction increases the activity of as-trocytes, which express only the isoform Dys1A that is reduced in the caudate of patients with schizophrenia. Astrocytic Dys1A disruption resulted in avolition and sensorimotor gating deficits, increased astrocytic dopamine D2 receptors and decreased dopaminergic tone within basal gan-glia. Notably, astrocytic Dys1A hypofunction disrupted dopamine dynamics linked to reward ex-pectancy and interconnected with astrocytes Ca2+ responses mainly in the globus pallidus externus (GPe). Finally, we proved these phenotypes were mediated by D2 receptors in astrocytes as their selective deletion in astrocytes either in GPe or SNc/VTA enhanced motivation and sensorimotor gating abilities as well as dopaminergic release in the GPe. Therefore, astrocytes control motivational and sensorimotor gating processes through Dys1A/D2-dependent mechanisms within the basal ganglia.

Spatiomolecular Characterization of Dopamine D2 Receptors Cells in the Mouse External Globus Pallidus

“…Moreover, D2R activation has been shown to regulate the activity of the glial transporter (GAT-3) facilitating GABA uptake by GPe astrocytes (56). Finally, although recent evidence unveil the presence of functional D2R in GPe astrocytes (57), the lack of detection of GFAP/HA-positive cells in the GPe suggest that, if any, basal D2R expression in GPe astrocytes is low.…”