Age-related GABAA receptor changes in rat auditory cortex

Auditory cortex (AI) shows age-related decreases in pre-synaptic markers for gamma-aminobutyric acid (GABA) and degraded AI neuronal response properties. Previous studies find age-related increases in spontaneous and driven activity, decreased spectral and directional sensitivity, and impaired novelty detection. The present study examined expression of GABA(A) receptor (GABA(A)R) subunit message, protein, and quantitative GABA(A)R binding in young, middle-aged, and aged rat AI, with comparisons with adjoining parietal cortex. Significant loss of GABA(A)R α(1) subunit message across AI layers was observed in middle-aged and aged rats and α(1) subunit protein levels declined in layers II and III. Age-related increases in GABA(A)R α(3) subunit message and protein levels were observed in certain AI layers. GABA(A)R subunits, including β(1), β(2), γ(1), γ(2s), and γ(2L), primarily, but not exclusively, showed age-related declines at the message and protein levels. The ability of GABA to modulate [(3)H]t-butylbicycloorthobenzoate binding in the chloride channel showed age-related decreases in peak binding and changes in desensitization kinetics. Collectively, age-related changes in GABA(A)R subunit composition would alter the magnitude and temporal properties of inhibitory synaptic transmission and could underpin observed age-related functional changes seen in the elderly.