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Working model of astrocyte-mediated LTD at cortico-dSPN synapses. HFS of deep Layer V of somatosensory cortex (1) induces glutamate release from cortical afferents that activates mGluR5 on astrocytes (2), leading to GPCR-IP3R2-mediated Ca2+ increases (3), and extracellular accumulation of astrocyte-derived adenosine (4). Adenosine activates A1R located on cortical afferents to suppress subsequent glutamate release, resulting in LTD (5).
