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 GABAA receptor (GABAAR) subunit message, protein, and quantitative GABAAR binding in young, middle-aged, and aged rat AI, with comparisons with adjoining parietal cortex. Significant loss of GABAAR α1 subunit message across AI layers was observed in middle-aged and aged rats and α1 subunit protein levels declined in layers II and III. Age-related increases in GABAAR α3 subunit message and protein levels were observed in certain AI layers. GABAAR subunits, including β1, β2, γ1, γ2s, and γ2L, primarily, but not exclusively, showed age-related declines at the message and protein levels. The ability of GABA to modulate [3H]t-butylbicycloorthobenzoate binding in the chloride channel showed age-related decreases in peak binding and changes in desensitization kinetics. Collectively, age-related changes in GABAAR 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.