Somatostatin interneurons inhibit excitatory transmission mediated by astrocytic GABAB and presynaptic GABAB and adenosine A1 receptors in the hippocampus.

GABAergic network activity has been established to be involved in numerous physiological processes and pathological conditions. Extensive studies have corroborated that GABAergic network activity regulates excitatory synaptic networks by activating presynaptic GABAB receptors (GABAB Rs). It is well documented that astrocytes express GABAB Rs and respond to GABAergic network activity. However, little is known about whether astrocytic GABAB Rs regulate excitatory synaptic transmission mediated by GABAergic network activity. To address this issue, we combined whole-cell recordings, optogenetics, calcium imaging, and pharmacological approaches to specifically activate hippocampal somatostatin-expressing interneurons (SOM-INs), a type of interneuron that targets pyramidal cell dendrites, while monitoring excitatory synaptic transmission in CA1 pyramidal cells. We found that optogenetic stimulation of SOM-INs increases astrocyte Ca2+ signaling via the activation of astrocytic GABAB Rs and GAT-3. SOM-INs depress excitatory neurotransmission by activating presynaptic GABAB Rs and astrocytic GABAB Rs, the latter inducing the release of ATP/adenosine. In turn, adenosine inhibits excitatory synaptic transmission by activating presynaptic adenosine A1 receptors (A1 Rs). Overall, our results reveal a novel mechanism that SOM-INs activation-induced synaptic depression is partially mediated by the activation of astrocytic GABAB Rs.

Chemogenetic manipulation of astrocytic activity: Is it possible to reveal the roles of astrocytes?

Astrocytes are the major glial cells in the central nervous system, but unlike neurons, they do not produce action potentials. For many years, astrocytes were considered supporting cells in the central nervous system (CNS). Technological advances over the last two decades are changing the face of glial research. Accumulating data from recent investigations show that astrocytes display transient calcium spikes and regulate synaptic transmission by releasing transmitters called gliotransmitters. Many new powerful technologies are used to interfere with astrocytic activity, in order to obtain a better understanding of the roles of astrocytes in the brain. Among these technologies, chemogenetics has recently been used frequently. In this review, we will summarize new functions of astrocytes in the brain that have been revealed using this cutting-edge technique. Moreover, we will discuss the possibilities and challenges of manipulating astrocytic activity using this technology.