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bioRxiv · 10.1101/098889

Potassium channels contribute to activity-dependent scaling of dendritic inhibition

Chang, J. T.·Higley, M. J.
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Abstract

GABAergic inhibition plays a critical role in the regulation of neuronal activity. In the neocortex, inhibitory interneurons that target the dendrites of pyramidal cells influence both electrical and biochemical postsynaptic signaling. Voltage-gated ion channels strongly shape dendritic excitability and the integration of excitatory inputs, but their contribution to GABAergic signaling is less well understood. By combining 2-photon calcium imaging and focal GABA uncaging, we show that voltage-gated potassium channels normally suppress the GABAergic inhibition of calcium signals evoked by back-propagating action potentials in dendritic spines and shafts of cortical pyramidal neurons. Moreover, the voltage-dependent inactivation of these channels leads to enhancement of dendritic calcium inhibition following somatic spiking. Computational modeling reveals that the enhancement of calcium inhibition involves an increase in action potential depolarization coupled with the nonlinear relationship between membrane voltage and calcium channel activation. Overall, our findings highlight the interaction between intrinsic and synaptic properties and reveal a novel mechanism for the activity-dependent scaling of GABAergic inhibition.\n\nSignificance StatementGABAergic inhibition potently regulates neuronal activity in the neocortex. How such inhibition interacts with the intrinsic electrophysiological properties of single neurons is not well-understood. Here we investigate the ability of voltage-gated potassium channels to regulate the impact of GABAergic inhibition in the dendrites of neocortical pyramidal neurons. Our results show that potassium channels normally reduce inhibition directed towards pyramidal neuron dendrites. However, these channels are inactivated by strong neuronal activity, leading to an enhancement of GABAergic potency and limiting the corresponding influx of dendritic calcium. Our findings illustrate a previously unappreciated relationship between neuronal excitability and GABAergic inhibition.

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Chang, J. T., Higley, M. J.. 2017-01-06. Potassium channels contribute to activity-dependent scaling of dendritic inhibition. https://doi.org/10.1101/098889

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