Abstracts

Biological aging is associated with an increasing incidence of functional deficits in multiple organ systems as well as a growing risk of disease. In the brain, age-related alterations in GABAergic inhibitory system may occur resulting in increased neuronal excitability and the generation of epileptiform discharges. The goal of this study was to determine whether there were significant age-related changes of GABAergic synaptic inhibition to pyramidal neurons of layer II/III of the sensorimotor cortex., Whole-cell patch clamp techniques were used to record postsynaptic currents (PSCs) and spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) from layer II/III pyramidal neurons in sensorimotor cortical slices of young adult (4 month old, n=9) and aged (20 month old, n=9) Fischer 344 rats. Analysis was performed on PSCs and sIPSCs recorded from 44 pyramidal neurons (young, n=23; aged, n=21) and mIPSCs recorded from 29 of the 44 pyramidal neurons (young, n=15; aged, n=14)., For aged animals, compared with young adult animals: 1) the amplitude of mIPSCs increased significantly ([sim]55% higher than that of young animals, 25.72[plusmn]2.50pA in young vs.39.87[plusmn]3.82pA in aged), whereas PSC and sIPSC amplitude had no significant change; 2) the 10-90% rise time of PSCs increased significantly ([sim]19% longer than that of young animals, 3.92[plusmn]0.29ms in young animals vs. 4.65[plusmn]0.20ms in aged animals)and sIPSCs ([sim]18% longer than that of young animals, 3.97[plusmn]0.26ms in young animals vs.4.66[plusmn]0.21ms in aged animals),whereas mIPSC 10-90% rise time had no significant change; 3) The PSC, sIPSC, and mIPSC decay time constant was similar; 4) The charge transfer of PSCs and sIPSCs was similar, whereas the mIPSC charge transfer demonstrated a trend toward increase ([sim]50% higher than that of young animals); 5) there were significant increases in the frequency of PSCs ([sim]130% higher than that of young animals), sIPSCs ([sim]127% higher than that of young animals), and mIPSCs ([sim]144% higher than that of young animals)., GABA[sub]A[/sub]-receptor mediated synaptic inhibition of sensorimotor cortex layer II/III pyramidal neurons is enhanced with age. This enhancement of GABAergic inhibitory synaptic transmission may lead to significant alterations in cortical signaling activity that may be associated with an increased propensity for epileptogenesis in the aging brain., (Supported by R01 NS046015 to KMK.)