Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age?dependent manner, normalizes GABA?activated currents in the tg?APPSwe mouse model of Alzheimer’s disease

Aim We examined if tonic ?-aminobutyric acid (GABA)-activated currents in primary hippocampal neurons were modulated by insulin wild-type and tg-APPSwe mice, an Alzheimer's disease (AD) model. Methods GABA-activated recorded dentate gyrus (DG) granule cells CA3 pyramidal brain slices, from 8 to 10 weeks old (young) mice dorsal DG adult, 5-6 10-12 (aged) months the absence or presence of insulin, whole-cell patch-clamp electrophysiology. Results In young (1 nmol/L) enhanced total spontaneous inhibitory postsynaptic current (sIPSCT) density both ventral cells. The extrasynaptic was only increased neurons. action potentials, miniature IPSC (mIPSC) frequency, consistent with regulation presynaptic GABA release. sIPSCT densities similar at but significantly decreased aged where normalized levels. relative littermates but, did decrease normalize current. Conclusion Insulin effects on signalling are selective while multifaceted context-based. Not is response related cell-type, axis-location, age animals also subtype neuronal inhibition involved, synaptic GABAA receptors-activated currents.