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bioRxiv · 10.1101/2025.06.05.657434

Dendritic inhibition terminates plateau potentials in CA1 pyramidal neurons

Vaasjo, L. O.·Kotermanski, S. E.·Patel, T.·Shi, H. J.·Machold, R.·Chamberland, S.
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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.

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Vaasjo, L. O., Kotermanski, S. E., Patel, T., Shi, H. J., Machold, R., Chamberland, S.. 2025-06-06. Dendritic inhibition terminates plateau potentials in CA1 pyramidal neurons. https://doi.org/10.1101/2025.06.05.657434

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