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Authors & Affiliations
Lissy Liebeskind, Knut Kirmse
Abstract
Spontaneous network activity is a conserved feature of the developing brain, and accumulating evidence indicates that it plays a critical role in neuronal circuit maturation. In the neonatal mouse hippocampus, spontaneous network activity in vitro comprises intermittent giant depolarizing potentials (GDPs) that alternate with periods of asynchronous activity. Spontaneous activity depends on depolarizing GABA, mediating mixed excitatory and inhibitory actions. However, little is known about how different GABAA receptor (GABAAR) subunit compositions contribute to spontaneous activity. Here, we investigate the impact of α5 subunit-containing GABAARs (α5-GABAARs) on spontaneous activity in hippocampal area CA1 using multi-neuron Ca2+ imaging, pharmacological manipulations and electrophysiological approaches in acute brain slices of neonatal mice. We found that the blockade of α5-GABAARs inhibits asynchronous activity in CA1, while leaving GDP generation unaffected. Conversely, blocking all GABAARs also suppresses asynchronous activity, but profoundly disinhibits cell recruitment during GDPs. Preliminary data indicate that α5-GABAARs mediate a small tonic current in CA1 pyramidal cells, whereas miniature GABAergic postsynaptic currents are generated in an α5‑GABAAR-independent manner. In summary, α5-GABAARs selectively enhance asynchronous spontaneous activity in developing CA1. Our findings suggest that distinct populations of GABAARs may differentially contribute to excitatory vs. inhibitory effects of GABAergic signaling.