Aim. GABA signaling regulates neuronal activity in the mammalian brain. As the hippocampus has a high density of receptors for metabolic hormones (Lathe 2001), they may potentially modulate neuronal excitability. Recently Jin et al. (2011) showed that insulin influences GABA signaling. GLP-1 is another metabolic hormone, secreted by intestinal L-cells, that affects brain function (During et al. 2003). We have examined whether GLP-1 and its analog Ex-4 can modulate GABA-evoked responses in the hippocampus. Methods. Whole-cell patch-clamp technique has been employed to record GABA-induced currents from 16–20-day-old rat brain slices. Results. The results show that application of submicromolar concentrations of GLP-1 or Ex-4 led to activation of tonic GABA-evoked currents and increased frequency of synaptic GABA- activated currents as compared to control. Ex-4 furthermore enhanced the tonic current activated by pre-application of diazepam. Ex-4 potentially acts on a subpopulation of GABAA channels that may differ from those that are sensitive to diazepam.

Conclusions: 

Our results demonstrate that GLP-1 and Ex-4 enhance GABA signaling in hippocampal neurons.

References: 

During, M.J., Cao, L., Zuzga, D.S., Francis, J.S., Fitzsimons, H.L., Jiao, X., Bland, R.J., Klugmann, M., Banks, W.A., Drucker, D.J. & Haile, C.N. 2003.Nat Med 9, 1173–1179. Jin, Z., Jin, Y., Kumar-Mendu, S., Degerman, E., Groop, L. & Birnir, B. 2011. PLoS One 6, e16188. Lathe, R. 2001. J Endocrinol 169, 205–231.