Recent studies with functional magnetic brain imaging showed different task-related patterns of brain activation and deactivation in aged as compared to young healthy subjects. We hypothesized that these changes of brain activation patterns might be due to age-dependent changes of neuronal excitability. Therefore, we experimentally studied the functional cortical inhibition by paired pulse stimulation in brain slices of young adult (3 months), aged adult (24 months) and old (36 months) male rats. Field potentials were evoked by application of double pulses at layer VI/white matter and recorded in layer II/III. We also analyzed the regional distribution of five major gamma-aminobutyric acid A (GABA(A)) receptor subunits (alpha1, alpha2, alpha3, alpha5, and gamma2) by immunohistochemistry. A reduced functional inhibition in aged as compared to young animals associated with an altered composition of GABA(A)-receptors, especially a reduction of subunit alpha5 in aged animals, was shown. The present study suggests that the age-dependent functional activation patterns and possibly also the cognitive and motor abilities are at least partially modulated by an age-dependent alteration of functional inhibition in the neocortex.
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