Astrocytes Modulate Somatostatin Interneuron Signaling in the Visual Cortex

At glutamatergic synapses, astrocytes respond to the neurotransmitter glutamate with intracellular Ca²⁺ elevations and the release of gliotransmitters that modulate synaptic transmission. While the functional interactions between neurons and astrocytes have been intensively studied at glutamatergic synapses, the role of astrocytes at GABAergic synapses has been less investigated. In the present study, we combine optogenetics with 2-photon Ca²⁺ imaging experiments and patch-clamp recording techniques to investigate the signaling between Somatostatin (SST)-releasing GABAergic interneurons and astrocytes in brain slice preparations from the visual cortex (VCx). We found that an intense stimulation of SST interneurons evokes Ca²⁺ elevations in astrocytes that fundamentally depend on GABA_B receptor (GABA_BR) activation, and that this astrocyte response is modulated by the neuropeptide somatostatin. After episodes of SST interneuron hyperactivity, we also observed a long-lasting reduction of the inhibitory postsynaptic current (IPSC) amplitude onto pyramidal neurons (PNs). This reduction of inhibitory tone (i.e., disinhibition) is counterbalanced by the activation of astrocytes that upregulate SST interneuron-evoked IPSC amplitude by releasing ATP that, after conversion to adenosine, activates A₁Rs. Our results describe a hitherto unidentified modulatory mechanism of inhibitory transmission to VCx layer II/III PNs that involves the functional recruitment of astrocytes by SST interneuron signaling.