biostudies-literatureGomez REuropean Research Councile2107026118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8536339biostudies-literatureUnknown118(35)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 inputProceedings of the National Academy of Sciences of the United States of AmericaNMDA receptor-BK channel coupling regulates synaptic plasticity in the barrel cortex.PMC8536339648936Gonzalez-Hernandez AJMaglio LEBartolome-Martin DRivero-Perez BGomez RGiraldez TfalseNMDA receptor-BK channel coupling regulates synaptic plasticity in the barrel cortex.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 input2021-01-01T00:00:00Z2021 Aug2025-04-04T22:42:55.351Z2025-04-04T22:42:55.351ZS-EPMC85363393445300410.1073/pnas.2107026118