GABA (g-aminobutyric acid) and its receptors have been shown to have a role in the central nervous system (CNS) control of metabolic homeostasis. Hypothalamic and hippocampal neurons in the CNS can sense and respond to changes in metabolic signals. The pancreatic hormone insulin, in addition to its critical role in peripheral glucose regulation, has effects on neuronal excitability and memory functions.

Objective: 

To investigate the effect of low, physiological concentration of insulin on GABA-mediated inhibition in rat hippocampal CA1 pyramidal neurons.

Methods: 

Rat hippocampal slices (P16-P22) were prepared and incubated with low concentration of insulin for 1, 2, and 3 hours. Standard whole-cell recording was performed.

Results: 

Insulin incubation decreased action potential firing of CA1 pyramidal neurons and increased both phasic and tonic currents mediated by GABAA receptors in a temporal manner. Application of the a5-subunit selective antagonist L655, 708 significantly blocked the insulin-induced tonic current.

Conclusions: 

Low concentration of insulin potentiates GABA-generated inhibition in hippocampal CA1 pyramidal neurons. Insulin modulates both synaptic and extrasynaptic currents and induces a new type of extrasynaptic GABAA receptor with distinct pharmacological properties.