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Effect of Sedentary Conditions on the Expression of GABAAα2 Receptor Subunits in Bulbospinal C1 and non‐C1 Neurons along the Rostrocaudal Extent of Rat Rostral Ventrolateral Medulla (RVLM)

Bulbospinal RVLM neurons play a crucial role in the regulation of sympathetic nerve activity and blood pressure, and can be characterized phenotypically as catecholaminergic (C1) or non‐catecholaminergic (non‐C1). Although excitatory in nature, the tonic activity of the RVLM is strongly influenced by the prevailing level of the inhibitory GABAergic tone. Following sedentary conditions, RVLM neurons also exhibit structural and functional plasticity in a region‐dependent manner, with enhanced dendritic branching and increased glutamate responsiveness in rostral versus caudal regions. Because withdrawal of GABAergic tone produces net excitation of RVLM neurons primarily via GABAA receptors, it is possible that sedentary conditions also alter GABA receptor expression in a region‐dependent manner. Thus, the purpose of the present study was to test the hypothesis that sedentary conditions reduce GABAA receptor expression in rostral regions of the RVLM. To this end, male Sprague‐Dawley rats were divided into sedentary (no wheels) and physically active (running wheels) conditions for 12 wks (n=4 ea). Spinal cord injections of cholera toxin B (CTB) labeled bulbospinal neurons. We examined coronal sections processed for triple‐labeling immunofluorescence using laser confocal microscopy, and quantified CTB‐positive C1 and non‐C1 neurons expressing the GABAAα2 receptor subunit. As expected, more bulbospinal C1 cells expressing GABAAα2 occurred in caudal versus rostral RVLM (p<0.05). Sedentary rats had fewer bulbospinal C1 cells that expressed GABA Aα2 only in the rostral most subregions of the RVLM when compared to active rats (p<0.05). The number of bulbospinal non‐C1 neurons also varied rostrocaudally. However, there were more non‐C1 neurons in rostral compared to caudal RVLM with no overt differences between sedentary versus active groups. Decreases in RVLM neurons expressing GABAA receptors in rostral RVLM are consistent with previous data demonstrating enhanced sympathetic outflow following sedentary conditions, which may in turn contribute to the increased incidence of cardiovascular disease in sedentary individuals.