NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex

Abstract

Significance N-methyl-D-aspartate (NMDA) receptors are critical triggers for neuronal plasticity. We show that large-conductance Ca2+- and voltage-gated K+ (BK) channels serve as feedback regulators of NMDA receptor–mediated calcium influx to shape NMDA receptor–mediated synaptic potentials and consequently elevate the threshold for triggering plasticity at a subset of synapses. Postsynaptic N-methyl-D-aspartate receptors (NMDARs) are crucial mediators of synaptic plasticity due to their ability to act as coincidence detectors of presynaptic and postsynaptic neuronal activity. However, NMDARs exist within the molecular context of a variety of postsynaptic signaling proteins, which can fine-tune their function. Here, we describe a form of NMDAR suppression by large-conductance Ca2+- and voltage-gated K+ (BK) channels in the basal dendrites of a subset of barrel cortex layer 5 pyramidal neurons. We show that NMDAR activation increases intracellular Ca2+ in the vicinity of BK channels, thus activating K+ efflux and strong negative feedback inhibition. We further show that neurons exhibiting such NMDAR–BK coupling serve as high-pass filters for incoming synaptic inputs, precluding the induction of spike timing–dependent plasticity. Together, these data suggest that NMDAR-localized BK channels regulate synaptic integration and provide input-specific synaptic diversity to a thalamocortical circuit.