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Age-related GABAA receptor changes in rat auditory cortex.

Donald M Caspary¹, Larry F Hughes, Lynne L Ling

¹Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA. dcaspary@siumed.edu

Neurobiology of Aging

|December 22, 2012

Summary

Aging auditory cortex shows significant changes in GABA(A) receptor subunit composition. These alterations in inhibitory neurotransmission may explain age-related declines in auditory processing and novelty detection in older individuals.

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Area of Science:

Neuroscience
Aging Research
Auditory System

Background:

Auditory cortex (AI) exhibits age-related functional decline, including reduced sensitivity and impaired novelty detection.
Previous research indicates decreased GABAergic markers and altered neuronal responses in aging AI.

Purpose of the Study:

To investigate age-related changes in GABA(A) receptor (GABA(A)R) subunit expression, protein levels, and binding in rat AI.
To compare these changes with adjacent parietal cortex across different age groups.

Main Methods:

Quantitative analysis of GABA(A)R subunit mRNA and protein expression in young, middle-aged, and aged rat AI.
Assessment of GABA(A)R binding kinetics using [(3)H]t-butylbicycloorthobenzoate.
Comparative analysis with parietal cortex tissue.

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Main Results:

Significant reduction in GABA(A)R α(1) subunit mRNA and protein in aged AI.
Upregulation of GABA(A)R α(3) subunit mRNA and protein in specific AI layers with age.
Age-related declines in message and protein for several other GABA(A)R subunits (β(1), β(2), γ(1), γ(2s), γ(2L)).
Decreased GABA-modulated chloride channel binding and altered desensitization kinetics in aged rats.

Conclusions:

Age-related alterations in GABA(A)R subunit composition significantly impact inhibitory synaptic transmission in the auditory cortex.
These molecular changes provide a potential basis for observed age-related deficits in auditory processing and cognitive functions like novelty detection.