State-dependent Activity of Barosensitive Adrenergic Neurons is Necessary for Blood Pressure Stability During Wakefulness and Postural Changes

Background: The modulation of the cardiovascular system is a fundamental manifestation of sleep-wake cycle, marked by an increase in blood pressure (BP) and heart rate (HR) when the animals are awake, especially during dynamic movements and exercise. Adrenergic neurons in the rostral ventrolateral medulla, named C1 neurons, drive sympathetic activity that regulates arterial BP. These neurons receive input from the pontine and hypothalamic network regulating sleep-wake cycle and from the mesencephalic locomotor region. However, there is limited evidence that C1 neurons exhibit vigilance- and/or locomotor-related activity as most of the experimental recordings of these neurons have been conducted in anesthetized conditions. Hypothesis: We hypothesized that C1 neuron activity is coupled with vigilance state and are necessary for the maintenance of BP during wakefulness, especially during dynamic movements. Methods: We used male and female adult Tyrosine-Hydroxylase-Cre transgenic rats and performed recordings of C1 neurons activity in conscious, freely behaving condition using in vivo calcium imaging (GCaMP7s). C1 neuron recordings were coupled with BP and EEG/EMG measurements. Additionally, we used genetically-targeted ablation (AAV-Ef1α-taCasp3-TEVp) to determine the role of C1 neurons in the regulation of BP during changes in arousal state and locomotor activity. Results: Hypotension induced with intravenous injections of sodium nitroprusside resulted in a large increase in C1 neuron activity (ΔF/F0: +14.8 ± 7 % from baseline, n=8), indicating their barosensitive nature. C1 neurons were quiescent during NREM sleep and increased their activity during transitions to wakefulness (ΔF/F0: +3.2 ± 1 % from NREM, n=8). After the ablation of C1 neurons (C1-Lesion, n=11), the sympathetic modulation of BP was reduced (LF-SAP, 5.2 ±2 vs. 2.1 ±1 mmHg2, p<0.0001) and BP was unstable in C1-lesion animals compared to control group, especially during wakefulness (coefficient of variation, 5.3 ±0.9 vs. 4.7 ±0.5 %, p=0.027). We also observed that C1 neuron activity transiently increased during rearing (ΔF/F0= +5 ±3%, n=6). Interestingly, we observed marked hypotension during rearing after the ablation of C1 neurons compared to controls (-12 ± 4 vs. -2 ± 4 mmHg fall in BP with rearing, N=5 vs 6, p=0.004), indicating that C1 neurons are activated during postural changes to stabilize BP. Summary: C1 neurons are activated during wakefulness and during postural changes; after ablation of C1 neurons, blood pressure is unstable, and the sympathetic modulation of BP is reduced. Conclusion: We conclude that the barosensitive C1 neurons are activated during arousal from sleep and postural changes and are necessary for maintaining blood pressure stability in these situations. This work was supported by National Institutes of Health Grant HL148004 to S.B.G.A. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.