Activity-Induced Changes in GABAA Receptor Subunit Expression in the Senescent Rat Brain

Ageing and senescence are commonly associated with a characteristic decline in cognitive and sensorimotor performance that can be decelerated by physical and mental activity. Experimental investigations in aged rats demonstrated that this sensorimotor decline coincides with a reduction in receptive field size and sensory stimulation thresholds which could be both reversed by activating housing conditions in an enriched environment. We here analyzed the effects of environmental enrichment on regional expression of GABAA receptor subunits in the very old brain. At the age of 33 months standard housed rats were transferred to an enriched environment for three months (EE) whereas controls were kept in standard cages further on (ST). At 36 months all rats were transcardially perfused and brains were processed for immunohistochemistry with antibodies against five major GABAA receptor subunits (α1, α2, α3, α5, and γ2). Regional expression of receptor subunits was semi-quantitatively evaluated using optical density measurements. Using this approach a significant increase in expression of subunits α3 and α5 was observed in EE animals compared with ST-housed controls. This increase was most prominent for subunit α3 and was restricted to the primary and secondary somatosensory cortex as well as to the forelimb and hindlimb representation cortex. Subunits α1, α2, and γ2 did not reveal any significant change in regional distribution. EE-induced alterations in subunit expression were not observed in the hippocampal formation. In a further series of experiments mRNA expression of these subunits was analyzed by rt-PCR. This study demonstrates a significant activity-induced plasticity of cortical GABAA receptors in the very old brain. The upregulation of subunits α3 and α5 which both are abundantly expressed in the cortex during early life might indicate a recapitulation of a juvenile expression pattern. These changes probably contribute to the sensorimotor plasticity found in very old rats following environmental enrichment