Astrocytic Gi-GPCR activation enhances stimulus-evoked extracellular glutamate

Astrocytes perform critical functions in the nervous system, many of which
are dependent on neurotransmitter-sensing through G protein-coupled
receptors (GPCRs). However, whether specific astrocytic outputs follow
specific GPCR activity remains unclear, and exploring this question is
critical for understanding how astrocytes ultimately influence brain
function and behavior. Here, we investigate the outputs of astrocytic
Gi-GPCRs, a family of GPCRs which we previously showed is sufficient to
increase slow-wave neural activity (SWA) during sleep when activated in
cortical astrocytes1. We focus on two putative outputs by astrocytes in
vivo, the regulation of extracellular glutamate and GABA, by combining
fiber photometry recordings of the extracellular indicators iGluSnFR and
iGABASnFR with astrocyte-specific chemogenetic Gi-GPCR activation. We find
that Gi-GPCR activation does not change spontaneous dynamics of
extracellular glutamate or GABA. However, Gi-GPCR activation does
specifically increase visual stimulus-evoked extracellular glutamate.
Together, these data point towards a complex relationship between
astrocytic inputs and outputs in vivo that may depend on behavioral
context. Further, they suggest an extracellular glutamate-specific
mechanism underlying some astrocytic Gi-GPCR-dependent behaviors,
including the regulation of sleep SWA.