Spontaneously opening GABA(A) receptors play a significant role in neuronal signal filtering and integration

Continuous (tonic) charge transfer through ionotropic receptors of γ-aminobutyric acid (GABA(A)Rs) is an important mechanism of inhibitory signalling in the brain. The conventional view has been that tonic GABA-ergic inhibitory currents are mediated by low concentrations of ambient GABA. Recently, however, it was shown that the GABA-independent, spontaneously opening GABA(A)Rs (s-GABA(A)Rs), may contribute significantly to the tonic GABA(A)R current. One of the common approaches to temporal lobe epilepsy (TLE) therapy is an increase of GABA concentration in the cerebrospinal fluid to augment tonic current through GABA(A)Rs. Such an increase, however, generates multiple side effects, which impose significant limitations on the use of correspondent drugs. In contrast, activation/deactivation of s-GABA(A)Rs in a GABA-independent manner may provide a mechanism of regulation of tonic conductance without modification of extracellular GABA concentration, thus avoiding connected side effects. Although s-GABA(A)Rs have been detected in our earlier work, it is unclear whether they modulate neural signalling, or, due to their independence from the neurotransmitter, they provide just a stable background effect without much impact on neural crosstalk dynamics. Here, we focused on the causal relationship between s-GABA(A)R activity and signal integration in the rat’s dentate gyrus granule cells to find that s-GABA(A)Rs play an important role in neural signal transduction. s-GABA(A)Rs shape the dynamics of phasic inhibitory responses, regulate the action potential generation machinery and control the coincidence detection window pertinent to excitatory input summation. Our results demonstrate that tonic inhibition delivered by s-GABA(A)Rs contributes to the key mechanisms that ensure implementation of neural signal filtering and integration, in a GABA-independent manner. This makes s-GABA(A)R a new and important actor in the regulation of long-term neural plasticity and a perspective target for TLE therapy.