Astrocytes in globus pallidus externa integrate sensory information through dopamine D2 receptors

The globus pallidus externa (GPe) is a basal ganglia structure with a high content of astrocytes compared to neighboring brain regions. Apart from its well-known role in locomotor behavior, recent studies showed that the GPe is also involved in cognitive functions, motivated behavior and sensory integration. The vast majority of studies has focused on neuronal subpopulations in GPe, while the function of the numerically superior astrocytes remain elusive. Recently, we showed that astrocytes in GPe express dopamine D2 receptors (D2Rs), and their selective manipulation can have profound effects on sensorimotor gating and dopamine (DA) levels in the region. Here, we aimed to understand the role of GPe astrocytes in sensory integration and how the interplay between astrocytic D2Rs and DA can mediate these phenomena. To answer our questions we employed a series of methods including calcium fiber photometry, optogenetic activation of DA neurons, conditioned KO approaches and behavioral testing, to selectively monitor and manipulate the activity of GPe astrocytes in freely moving mice. We found that astrocytes increase their activity in response to DA neuron activation in a frequency-dependent manner. Sensory stimuli of different modalities induce distinct increases in astrocytic activity and these responses are modulated by GPe astrocytic D2Rs. Finally, ablating D2Rs from GPe astrocytes does not affect locomotor activity, but alters sensorimotor gating. Our study sheds light on the functional role of astrocytes in GPe and unravels a previously unexplored interplay between DA and astrocytic activity in mediating sensory integration and behavioral output.