Introduction: 

GABA (gamma-aminobutyric acid) is the predominant inhibitory neurotransmitter in the central nervous system (CNS). It binds to GABA-A receptors (GABA-A channels) and opens their chloride channel. GABA in the brain is commonly associated with fast, point-to-point form of signaling called synaptic transmission but GABA also participates in another slower and more diffuse, tonic form of signaling that is mediated by GABA-A channels outside of synapses, the extrasynaptic GABA-A channels. Our research is focused on the induction, function and pharmacology of these extrasynaptic channels.

Methods: 

We use the patch-clamp technique to measure the currents through single-channels or populations of channels. In the synaptic cleft, mM GABA activates postsynaptic GABA-A channels whereas the extrasynaptic GABA-A channels are continuously exposed to sub-microM GABA and modulate the basal excitability of neurons.

Results: 

Our results show that insulin induces supersensitive GABA-A channels in hippocampal neurons that have novel pharmacology (1) whereas the incretin GLP-1 and its analog exendin 4 enhance both synaptic and tonic currents.

Conclusion: 

Metabolic hormones significantly affect the inhibitory drive of CNS neurons.