While neurons principally mediate brain function, astrocytes are emerging as cells with important neuromodulatory actions in brain physiology. In addition to homeostatic roles, astrocytes respond to neurotransmitters with calcium transients stimulating the release of gliotransmitters that regulate synaptic and neuronal functions. We investigated astrocyte-neuronal network interactions in vivo by combining two-photon microscopy to monitor astrocyte calcium and electrocorticogram to record neuronal network activity in the somatosensory cortex during sensory stimulation. We found astrocytes respond to sensory stimuli in a stimulus-dependent manner. Sensory stimuli elicit a surge of neuronal network activity in the gamma range (30–50 Hz) followed by a delayed astrocyte activity that dampens the steady-state gamma activity. This sensory-evoked gamma activity increase is enhanced in transgenic mice with impaired astrocyte calcium signaling and is decreased by pharmacogenetic stimulation of astrocytes. Therefore, cortical astrocytes respond to sensory inputs and regulate sensory-evoked neuronal network activity maximizing its dynamic range.
Bibliographical noteFunding Information:
We would like to thank Dana Deters, Stephanie Nistler, Ruth Quintana, and Anshika Rai for technical support; Michelle Corkrum, Caitlin Durkee, Ana Covelo, Mario Martin-Fernandez, and Austin Ferro for helpful suggestions; Mark Sanders, Guillermo Marques, and Jason Mitchell at the University of Minnesota–University Imaging Centers for assistance using the Leica SP5 multiphoton upright microscope; Erin Larson at the MnDRIVE Optogenetics Core at the University of Minnesota for technical support; and Ju Chen for generously donating the IP3R2−/− mice. Viral vectors used in this study were generated by the University of Minnesota Viral Vector and Cloning Core (Minneapolis, MN). This work was supported by National Institutes of Health-NINDS (R01NS097312), National Institutes of Health-NIDA (R01DA048822) and National Institutes of Health-MH (R01MH119355) to A.A.; NIH-NIA (1F31AG057155) and the University of Minnesota Doctoral Dissertation Fellowship to J.L.; Salvador de Madariaga Program (PRX19/ 00646) and Ministerio de Ciencia, Innovación y Universidades (BFU2017-88393-P), Spain, and AEI/FEDER, EU, to E.D.M.; National Institutes of Health-MH (R01MH119355) to P.K.; Ministerio de Economía y Competitividad (BFU2016-80665-P), Spain, Ayudas para la Movilidad de Investigadores M-BAE (BA15/00078) del Instituto de Salud Carlos III, Spain, and co-funded by FEDER (“A way to make Europe”) to J.A.