期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：35
DOI：10.1073/pnas.2107026118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
N-methyl-D-aspartate (NMDA) receptors are critical triggers for neuronal plasticity. We show that large-conductance Ca
2+- 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 Ca
2+- 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 Ca
2+ 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.
