Selective Stimulation of Astrocyte Calcium In Situ Does Not Affect Neuronal Excitatory Synaptic Activity

SummaryAstrocytes are considered the third component of the synapse, responding to neurotransmitter release from synaptic terminals and releasing gliotransmitters—including glutamate—in a Ca2+-dependent manner to affect neuronal synaptic activity. Many studies reporting astrocyte-driven neuronal activity have evoked astrocyte Ca2+ increases by application of endogenous ligands that directly activate neuronal receptors, making astrocyte contribution to neuronal effect(s) difficult to determine. We have made transgenic mice that express a Gq-coupled receptor only in astrocytes to evoke astrocyte Ca2+ increases using an agonist that does not bind endogenous receptors in brain. By recording from CA1 pyramidal cells in acute hippocampal slices from these mice, we demonstrate that widespread Ca2+ elevations in 80%–90% of stratum radiatum astrocytes do not increase neuronal Ca2+, produce neuronal slow inward currents, or affect excitatory synaptic activity. Our findings call into question the developing consensus that Ca2+-dependent glutamate release by astrocytes directly affects neuronal synaptic activity in situ.