Reduced GABA(A) receptor-mediated tonic inhibition in aged rat auditory thalamus

Age-related deficits in detecting and understanding speech, which can lead to social withdrawal and isolation, have been linked to changes in the central auditory system. Many of these central age-related changes involve altered mechanisms of inhibitory neurotransmission, essential for accurate and reliable auditory processing. In sensory thalamus, GABA mediates fast (phasic) inhibition via synaptic GABA(A) receptors (GABA(A)Rs) and long-lasting (tonic) inhibition via high-affinity (extrasynaptic) GABA(A)Rs, which provide a majority of the overall inhibitory tone in sensory thalamus. Due to a delicate balance between excitation and inhibition, alteration of normal thalamic inhibitory function with age and a reduction of tonic GABA(A)R-mediated inhibition may disrupt normal adult auditory processing, sensory gating, thalamocortical rhythmicity, and slow-wave sleep. The present study examines age-related homeostatic plasticity of GABA(A)R function in auditory thalamus or the medial geniculate body (MGB). Using thalamic slices from young adult (3-8 months) and aged (28-32 months) rats, these studies found a 45.5% reduction in GABA(A)R density and a 50.4% reduction in GABA(A)R-mediated tonic whole cell Cl(-) currents in the aged MGB. Synaptic GABA(A)R-mediated inhibition appeared differentially affected in aged lemniscal and nonlemniscal MGB. Except for resting membrane potential, basic properties were unaltered with age, including neuronal Cl(-) homeostasis determined using the gramicidin perforated patch-clamp method. Results demonstrate selective significant age-dependent deficits in the tonic inhibitory tone within the MGB. These data suggest that selective GABA(A)R subtype agonists or modulators might be used to augment MGB inhibitory neurotransmission, improving speech understanding, sensory gating, and slow-wave sleep for a subset of elderly individuals.