Astrocyte Signaling Gates Long-Term Depression at Corticostriatal Synapses of the Direct Pathway
Anna Cavaccini, Caitlin A. Durkee, Paulo Kofuji, Raffaella Tonini, Alfonso Araque
Abstract
Despite extensive research into understanding synaptic mechanisms of striatal plasticity, the functional role played by astrocytes in this region remains to be fully elucidated. It was recently demonstrated that high-frequency stimulation (HFS) of cortical inputs induced long-term depression (LTD) mediated by adenosine A1 receptor (A1R) activation at corticostriatal synapses of the direct pathway [cortico-striatal projection neuron (dSPN)] in the dorsolateral striatum (DLS). Because astrocyte-derived adenosine has been shown to regulate synaptic transmission in several brain areas, we investigated whether this form of neuron-astrocyte signaling contributes to synaptic plasticity in the DLS of male and female mice. We found that cortical HFS increases calcium (Ca 21 ) levels in striatal astrocytes through activation of metabotropic glutamate receptor type 5 (mGluR5) signaling and that this astrocyte-mediated response is necessary for A1R-mediated LTD. Consistent with this, astrocyte activation with G q designer receptors exclusively activated by designer drugs (DREADDs) induced A1R-mediated synaptic depression at cortico-dSPN synapses. Together, these results indicate that astrocytes are integral elements of striatal A1Rmediated LTD.