Parallel astrocyte calcium signaling modulates olfactory bulb responses

Abstract

Astrocytes are the most abundant glial cell in the central nervous system. They modulate synaptic function through a variety of mechanisms, and yet remain relatively understudied with respect to overall neuronal circuit function. Exploiting the tractability of the mouse olfactory system, we manipulated astrocyte activity and examined how astrocytes modulate olfactory bulb responses. Toward this, we genetically targeted both astrocytes and neurons for in vivo widefield imaging of Ca²⁺ responses to odor stimuli. We found that astrocytes exhibited odor response maps that overlap with excitatory neuronal activity. By manipulating Ca²⁺ activity in astrocytes using chemical genetics we found that odor-evoked neuronal activity was reciprocally affected, suggesting that astrocyte activation inhibits neuronal odor responses. Subsequently, behavioral experiments revealed that astrocyte manipulations affect both odor detection threshold and discrimination, suggesting that astrocytes play an active role in olfactory sensory processing circuits. Together, these studies show that astrocyte calcium signaling contributes to olfactory behavior through modulation of sensory circuits.