Effect of Sedentary Conditions on the Rostrocaudal Expression of the NMDA NR1 Receptor Subunit in Bulbospinal C1 and non‐C1 Neurons of the Rat Rostral Ventrolateral Medulla (RVLM)

Abstract

Bulbospinal RVLM neurons directly innervate sympathetic preganglionic cells and therefore play important roles in the regulation of sympathetic nerve activity and blood pressure. RVLM neurons are divided phenotypically into catecholaminergic (C1) and non‐catecholaminergic (non‐C1).Previous studies from our laboratory reported that the RVLM of sedentary compared to physically active rats demonstrates greater structural and functional neuroplasticity in a subregion‐specific manner. For example, RVLM neurons from sedentary versus physically active rats exhibit greater dendritic branching and elicit greater sympathoexcitation upon direct stimulation with glutamate in rostral versus caudal RVLM. Bulbospinal RVLM neurons also express NMDA receptors and could contribute to inactivity‐induced neuroplasticity and enhanced sympathetic activation.The purpose of the present study was to test the hypothesis that sedentary conditions increase NMDA NR1 subunit expression in the RVLM in a subregion‐dependent manner. Male Sprague‐Dawley rats were sedentary (no running wheels) or physically active (free access to running wheels) for 10–12 wks (n=6 ea). Spinal cord injections of cholera toxin B (CTB)‐labeled bulbospinal RVLM neurons. We examined coronal sections for triple‐label immunofluorescence by laser confocal microscopy, and quantified CTB‐positive C1 and non‐C1 neurons expressing the NR1 receptor subunit.As expected from previous work, significantly more bulbospinal C1 neurons were positive for NR1 in the caudal RVLM compared to rostral RVLM in both experimental groups (p<0.001). Also as expected, more non‐C1 neurons immunoreactive for NR1 were in the rostral compared to caudal RVLM (p<0.001). Interestingly, sedentary rats demonstrated a strong trend for a higher percentage of C1 cells and significantly lower percentage of non‐C1 cells positive for NR1 in rostral RVLM when compared to active animals (p=0.067 and p=0.0048, respectively). In contrast, there were no overt differences between sedentary versus active rats in the percentage of C1 and non‐C1 cells positive for NR1 in caudal RVLM.Preliminary western blotting data showed lower expression of PSD95 (an excitatory post‐synaptic density protein) in sedentary versus active animals (0.89±0.15 vs. 1.64±0.24, PSD95/GAPDH, respectively), suggesting differential synaptic/extrasynaptic localization of glutamate receptors, including NR1, in sedentary and active groups.The greater number of NR1‐positive, bulbospinal C1 neurons in rostral RVLM of sedentary rats is consistent with our hypothesis and previous data showing enhanced SNA following activation of glutamate receptors in sedentary vs. active rats. Sedentary conditions may also enhance excitation of RVLM neurons by altering the composition of NMDAR subunits, their synaptic/extrasynaptic localization, trafficking, or expression of synapse‐related proteins and/or transporters.Support or Funding InformationHL096787‐08; AHA25810010This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.