Assessment of Neuronal Activity in the Rostral Ventrolateral Medulla (RVLM) of Conscious Rats

Hyperactive bulbospinal neurons in the RVLM and elevated sympathetic activity likely contribute to cardiovascular disease (CVD). Measuring RVLM neuronal activity in conscious rats would represent a major advance in understanding brain‐related CVD. The present study addressed this by developing manganese (Mn 2+ ) enhanced magnetic resonance imaging (MEMRI). Mn 2+ , a paramagnetic ion, enters active neurons via Ca 2+ channels and with MRI, allows visualization and quantification of neuronal activity. The purposes of this study were to use MEMRI to: 1) identify regions in RVLM with tonically active neurons, 2) characterize a time course of Mn 2+ in RVLM after systemic injection, 3) evaluate the sensitivity of MEMRI by varying dose, and 4) compare Mn 2+ in rostral vs caudal RVLM. We hypothesized that Mn 2+ increases in RVLM 1 d after i.p. injection; is dose‐dependent; and exhibits rostrocaudal variation. Tract‐tracing and direct RVLM injection anatomically and functionally confirmed RVLM on MRI images. Ten male SD rats were administered MnCl 2 (33 or 66 mg/kg i.p., n=5 ea). MRI scans on a 7T ClinScan demonstrated increased Mn 2+ in RVLM at 1 d (p=0.002) and was higher after 66 mg/kg vs 33mg/kg (p=0.019). Mn 2+ returned to baseline by 15 and 22 days (33 and 66 mg/kg, respectively). After 66 mg/kg, increased Mn 2+ occurred in more rostral vs caudal regions of RVLM (p=0.004), consistent with our previous dendritic branching study. Results highlight MEMRI as a viable and powerful new method for examining neuronal activity in the RVLM of conscious rats and understanding mechanisms related to brain‐related CVD.