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Tonic GABAergic activity facilitates dendritic calcium signaling and short-term plasticity

Chiu, C.; Morse, T.; Nani, F.; Knoflach, F.; Hernandez, M.-C.; Jadi, M.; Higley, M.

2020-04-24 neuroscience
10.1101/2020.04.22.055137 bioRxiv
Show abstract

Brain activity is highly regulated by GABAergic activity, which acts via GABAARs to suppress somatic spike generation as well as dendritic synaptic integration and calcium signaling. Tonic GABAergic conductances mediated by distinct receptor subtypes can also inhibit neuronal excitability and spike output, though the consequences for dendritic calcium signaling are unclear. Here, we use 2-photon calcium imaging in cortical pyramidal neurons and computational modeling to show that low affinity GABAARs containing an 5 subunit mediate a tonic hyperpolarization of the dendritic membrane potential, resulting in deinactivation of voltage-gated calcium channels and a paradoxical boosting of action potential-evoked calcium influx. We also find that GABAergic enhancement of calcium signaling modulates short-term synaptic plasticity, augmenting depolarization-induced suppression of inhibition. These results demonstrate a novel role for GABA in the control of dendritic activity and suggest a mechanism for differential modulation of electrical and biochemical signaling.

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