GABA-activated slow spontaneous inhibitory postsynaptic currents are decreased in dorsal hippocampal dentate gyrus granule cells in an aged mouse model of Alzheimer's disease

Background Synaptic transmission dysfunction is associated with a range of neurological disorders, including Alzheimer's disease (AD). However, the role of gamma-aminobutyric acid (GABA)-mediated synaptic inhibition in AD has not been fully explored. Objective We studied basal, GABA-activated slow spontaneous synaptic currents (sIPSCs) in dentate gyrus (DG) granule cells in the dorsal hippocampus of an AD mouse model (tg-APPSwe) and investigated insulin's modulatory effects. Methods GABA-activated slow sIPSCs were recorded in the DG granule cells by whole-cell patch-clamp recordings in dorsal hippocampal brain slices from 5-6 (adult) and 10-12 (aged) months old wild-type (WT) and AD mice, in the presence or absence of insulin (1 nM). Results The median 10-90% rise time of slow sIPSCs significantly decreased with age (10-12 months vs. 5-6 months) only in AD mice. The median amplitude of the slow sIPSCs was decreased in adult and aged AD mice as compared to WT mice whereas the slow sIPSCs frequency was only reduced in the aged WT mice. The median 63% decay time and total current density of the slow IPSCs was significantly decreased in the aged AD mice as compared to both WT mice and to the adult AD mice. Insulin application exerted no effect on slow sIPSCs properties in any of the animal groups. Conclusions The characteristics of the slow sIPSCs recorded in DG granule cells of dorsal hippocampus from WT and AD mice are altered by age- and disease-state, whereas insulin has negligible effects.