Feature Article: Selective modulation of tonically active GABA

Here we study intracellular mechanisms which regulate inhibitory signaling delivered through continuously (tonically) open ionotropic receptors of γ-aminobutyric acid (GABA) of dentate gyrus granule cells (DGCs). We found that, apart of classical GABA-A receptors (GABAARs) which can be activated by GABA binding, a significant part of tonic inhibitory current is delivered by newly discovered spontaneously opening GABAARs (s-GABAARs), which enter active state without binding of GABA. We have also found that conventional GABAARs and s-GABAARs are regulated by different intracellular mechanisms, which may overlap and thus induce various signaling repercussions. Our results demonstrate that s-GABAARs play a key role in the mechanism that implements DGCs functional role in the brain. On top of that, since regulatory mechanisms under study are affected in a number of pathological states, our results may have broad implications for treatment of neurological disorders.