Abstract
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.
Highlights
| large-conductance calcium- and voltage-activated potassium channels | | functional coupling ion channel macromolecular complexes synaptic plasticity
To determine whether functional N-methyl-D-aspartate receptors (NMDARs)–BK coupling plays a role in synaptic transmission, and potentially synaptic plasticity, we investigated the thalamocortical synapses at basal dendrites of barrel cortex (BC)-L5PNs
To investigate whether NMDA receptors are functionally coupled to other channel types in the basal dendrites of BC-L5PNs, we obtained whole-cell voltage-clamp recordings from pyramidal neurons located beneath layer 4 barrels in acute mouse brain slices (n = 108) (Fig. 1A)
Summary
| large-conductance calcium- and voltage-activated potassium channels | | functional coupling ion channel macromolecular complexes synaptic plasticity. Together, these characteristics confer postsynaptic NMDARs with the ability to detect and decode coincidental activity of pre- and postsynaptic neurons: presynaptic glutamate release brings about the occupation of the agonist-binding site and AMPAR-driven postsynaptic depolarization, removing the voltage-dependent Mg2+ block. These characteristics confer postsynaptic NMDARs with the ability to detect and decode coincidental activity of pre- and postsynaptic neurons: presynaptic glutamate release brings about the occupation of the agonist-binding site and AMPAR-driven postsynaptic depolarization, removing the voltage-dependent Mg2+ block The coincidence of these two events leads to NMDAR activation and a Ca2+ influx through the channel [8, 9], which initiates several forms of synaptic plasticity [10, 11]. In basal dendrites of BC-L5PN, the coactivation of neighboring dendritic inputs can initiate NMDAR-mediated dendritically restricted spikes characterized by large Ca2+ transients and long-lasting depolarizations [28,29,30], providing the appropriate environment for BK activation
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