Astrocytes are the most abundant cell population in the central nervous system and have various important roles in brain function.
Processes of astrocytes contact with neuronal synapses and communicate with neurons via G coupled receptors (GPCR) on astrocytes. Since astrocytes express various Gq-GPCR, neurotransmitters from synapses induce release of calcium from intracellular store and modulate astrocytic activities in vitro and in vivo.
On the other hand, even though astrocytic calcium signaling was thought to modulate neuronal activities by releasing gliotransmitters, recent studies showed that increasing or obliterating astrocytic Gq-GPCR mediated calcium signaling did not alter synaptic plasticity in vitro. Thus, it is still unclear whether astrocyte can modulate neuronal function or not.
To further understand the role of astrocyte in neuronal function, I investigate the effect of astrocytic activation on neuronal function in visual cortex in vivo. To selectively activate astrocytes in vivo, I used a new genetically modified mouse line, GFAP-hM3Dq mouse that express engineered muscarinic Gq-GPCR (hM3Dq receptor) under the control of an astrocytic GFAP promoter. This Gq-GPCR is not activated by any known endogenous ligand, but is activated by synthetic drug, clozapine-N-oxide (CNO) which can cross blood brain barrier. In this talk, I will introduce my recent results about this study, and technical advances about imaging system and genetically encoded calcium indicators.