Abstract
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABAB receptor-mediated Ca2+ elevations, respectively. Furthermore, the astrocyte response depresses upon parvalbumin interneuron repetitive stimulations and potentiates upon somatostatin interneuron repetitive stimulations, revealing a distinguished astrocyte plasticity. Remarkably, the potentiated response crucially depends on the neuropeptide somatostatin, released by somatostatin interneurons, which activates somatostatin receptors at astrocytic processes. Our study unveils, in the living brain, a hitherto unidentified signaling specificity between interneuron subtypes and astrocytes opening a new perspective into the role of astrocytes as non-neuronal components of inhibitory circuits.
Highlights
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits
We induced in PV interneurons of adult PV-Cre mice or SST interneurons of adult SST-Cre mice, the selective expression of the light-gated cation channel channelrhodopsin-2 (ChR2)[17] (Supplementary Fig. 1a–d) and in astrocytes the sparse expression of GCaMP6f (Supplementary Fig. 2a, b), a genetically encoded Ca2+ indicator (GECI)[18,19,20] (ChR2-PV-GCaMP6f or ChR2-SST-GCaMP6f mice, see Methods)
In somatosensory cortex (SSCx) slice preparations, we found that the increased Ca2+ elevations induced by interneuron signaling in the different astrocytic compartments, including microdomains, were mediated by activation of GABAB receptors (GABABRs) because they were abolished by the specific GABABR antagonist SCH50911 (Supplementary Figs. 7 and 9)
Summary
The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. A large diversity of interneurons in terms of morphology, connectivity, molecular and functional properties ensures a signaling specificity to surrounding neurons These unique features allow the different GABAergic interneurons to strictly control local network excitability and modulate synaptic transmission[1,2]. Astrocytes have been proposed to crucially affect GABAergic synaptic transmission[14,15,16], but whether the various interneuron classes, which warrant the specificity of GABAergic signaling to postsynaptic neurons, signal to astrocytes is a question that remains completely unexplored We here address this issue in the mouse somatosensory cortex (SSCx) and study the signaling to astrocytes of PV and SST interneurons by combining optogenetics with 2-photon Ca2+ imaging in in vivo and in situ slice experiments
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