Dendritic inhibition terminates plateau potentials in CA1 pyramidal neurons

Abstract

In CA1 pyramidal neurons (CA1-PYRs), plateau potentials control synaptic plasticity and the emergence of place cell identity. Here, we show that dendritic inhibition terminates plateaus in an all-or-none manner. Plateaus were initially resistant to inhibition but became increasingly susceptible to termination as they progressed. Between two distinct subtypes of dendrite-targeting interneurons, OLMNdnf generated slower postsynaptic currents that terminated plateaus more effectively than OLM2. Voltage-gated Ca2+ channels (VGCCs) were necessary for plateaus, which were prolonged by blocking small-conductance Ca2+-activated K+ channels (SK). A single-compartment model with these two conductances recapitulated core experimental findings and provided a mechanistic explanation for terminations. Plateaus arose from VGCCs maintained in the active state by sustained Ca2+ influx, a positive feedback loop that was quasi-balanced by ISK. Inhibition terminated plateaus by driving the membrane potential below a dynamic threshold to deactivate VGCCs and end the positive feedback loop. Lastly, two-photon Ca2+ imaging showed that plateaus evoke large dendritic Ca2+ transients that were graded by terminations. Overall, our results demonstrate how the feedback inhibitory circuit interacts with intrinsic cellular mechanisms to regulate plateau potentials and shape dendritic Ca2+ signals in CA1-PYRs.