Chemogenetic Approaches to Study Astrocytes at Glutamatergic Synapses

Chemogenetic modulation, via the use of designer receptors exclusively activated by designer drugs (DREADDs), is an established in vivo approach that allows cell-type-specific and spatiotemporally defined modulation of the brain. It combines both a genetic and a pharmacological aspect and can be used in multiple cell types such as neurons and glia. Several DREADDs have been developed, of which the muscarinic G-protein-coupled receptor DREADDs are the most frequently used. We will focus on viral vectors as delivery approach of the receptors and will describe the method for intracranial delivery of viral vectors in detail. Several aspects need to be considered regarding the choice of the DREADD agonist upon its administration. Next, we will describe the protocol that has been used for the visualization of DREADDs ex vivo. Through the measurement of local field potentials in hippocampal slices, it has been successfully demonstrated that astrocytic Gq- and Gi-DREADD modulation induces long-term synaptic potentiation. Finally, we will elaborate on other approaches to study chemogenetic modulation of astrocytes at glutamatergic synapses.