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 in CA1-PYRs recorded in acute hippocampal slices from mice of either sex. Plateaus were initially resistant to inhibition but became increasingly susceptible to termination as they progressed. Two subtypes of dendrite-targeting oriens-lacunosum moleculare (OLM) interneurons, accessed in transgenic mice based on the expression of the genes Ndnf or Chrna2 (OLM Ndnf and OLM α2 , respectively), could terminate plateau potentials. OLM Ndnf generated slower postsynaptic currents that terminated plateaus more effectively than OLM α2 . Voltage-gated Ca 2+ channels (VGCCs) were necessary for plateaus, which were prolonged by blocking small-conductance Ca 2+ –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 Ca 2+ influx, a positive feedback loop that was quasi-balanced by I SK . Inhibition terminated plateaus by driving the membrane potential below a dynamic threshold to deactivate VGCCs and end the positive feedback loop. Similar all-or-none termination dynamics were observed for plateaus evoked under cholinergic modulation. Lastly, two-photon Ca 2+ imaging showed that plateaus evoke large dendritic Ca 2+ 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 Ca 2+ signals in CA1-PYRs.