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 regulation of GABAergic inhibition.
Highlights
Inhibition in the neocortex is primarily mediated by the neurotransmitter gamma-aminobutyric acid (GABA) through synaptic contacts made by interneurons
In order to investigate the impact of potassium channels on dendritic inhibition, we performed simultaneous whole-cell current clamp recordings and two-photon calcium imaging of back-propagating action potentials (bAPs)-evoked dendritic Ca2+ transients in layer 5 pyramidal neurons (L5PNs) of mouse visual cortex (Fig. 1A)
We focused on the proximal apical dendrite, as single action potentials reliably propagate through this region
Summary
Inhibition in the neocortex is primarily mediated by the neurotransmitter gamma-aminobutyric acid (GABA) through synaptic contacts made by interneurons. These synapses are distributed across the entire somatodendritic arbor and work to counteract excitatory glutamatergic input. One important function of dendritic inhibition, in addition to action potential regulation, is the regulation of dendritic calcium signals which are thought to play an instructive role in synaptic plasticity (Tsubokawa and Ross 1996; Palmer et al 2012; Chiu et al 2013). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
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