NEURON–ASTROCYTE SIGNALING MECHANISMS SUPPORTING SPIKE TIMING-DEPENDENT LONG-TERM POTENTIATION IN THE SOMATOSENSORY CORTEX

Spike timing-dependent plasticity (STDP) is a fundamental learning rule that shapes synaptic refinement, learning, and memory during development. Although multiple forms of presynaptic spike timing-dependent long-term depression (t-LTD) have been extensively studied, the mechanisms underlying postsynaptic STDP in the somatosensory cortex remain poorly understood. Previous studies have identified the signaling pathways required for the induction of developmental t-LTD at L2/3–L2/3 synapses in the juvenile mouse somatosensory cortex, a form of plasticity that is restricted to early postnatal stages and is subsequently lost. In the present work, we investigated the cellular and molecular mechanisms underlying a form of spike timing-dependent long-term potentiation (t-LTP) at these synapses using brain slices from mice of either sex. We found that this t-LTP is expressed postsynaptically and requires the activation of ionotropic NMDA receptors containing the GluN2A and GluN2B subunits. In addition, inhibition of protein kinase A signaling blocks t-LTP, indicating that PKA activity is necessary for its expression. Furthermore, we demonstrate that astrocytes play a critical role in the induction of this plasticity, as both astrocytic calcium signaling and gliotransmitter release are required for t-LTP expression. Finally, we show that nitric oxide (NO) released from the postsynaptic neuron, together with NO-dependent signaling in astrocytes, is necessary for the induction of t-LTP. Together, these results identify a coordinated neuron–astrocyte signaling mechanism underlying spike timing-dependent long-term potentiation at L2/3–L2/3 synapses in the somatosensory cortex.