Chronic vagotomy alters cardiorespiratory responses and blunts nTS neuronal calcium responses to vagal afferent stimulation

Sensory information from the heart and lungs travels to the brain via afferents of the paired vagus nerves. The first site of integration of this input is the nucleus tractus solitarii (nTS) of the brainstem, an important contributor to cardiorespiratory function, and site of neuroplasticity. We have shown that decreasing input to the nTS via unilateral vagus nerve transection (vagotomy) induces morphological changes in nTS glia, which may contribute to neuroplasticity via altered glutamate regulation. Other studies have shown decreased synaptic transmission in vitro after vagotomy, suggesting that the decreased afferent input alters nTS neuronal function. However, the mechanisms behind post-vagotomy changes are not well understood. We hypothesized that chronic vagotomy alters cardiorespiratory responses to vagal afferent stimulation via blunted nTS neuronal activity. Male Sprague-Dawley rats (6-wk) underwent right cervical vagus nerve transection (or sham surgery) caudal to the nodose ganglion. After one week, rats were anesthetized, ventilated, and instrumented to measure mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Intact vagus nerves were transected acutely to prevent efferent-mediated responses. To determine whether vagotomy alters cardiorespiratory responses to stimulation, left and right vagus nerves were stimulated (20 sec, 0.2mA, 2-50 Hz, 0.5ms) and responses recorded for 5 minutes. In sham and vagotomy, stimulation induced variable MAP, HR, and SSNA responses, and decreased PhrNA. Vagotomy augmented the stimulation-induced increases in HR, MAP, and SSNA compared to the chronically intact side and compared to shams. However, vagotomy blunted the stimulation-induced decreases in PhrNA. To test whether these altered responses are due to changes in nTS neuronal function, nTS neuronal Ca 2+ responses to vagal stimulation were measured via fiber photometry in a subset of animals (n=6) that had previously been nanoinjected with a GCaMP-expressing virus in the nTS. Vagal stimulation increased Ca 2+ fluorescence in the nTS. Across both groups and sides, afferent stimulation increased Ca 2+ within 190ms, followed by changes in SSNA (480ms), PhrNA (820ms), MAP (2.1s), and HR (3.8s). There were no differences in response latency between groups or sides. The elevation of Ca 2+ correlated to cardiorespiratory responses to stimulation (R2 > 0.8). Unilateral vagotomy blunted neuronal Ca 2+ (ΔF/F) in response to stimulation compared to stimulation of the chronically intact side (p=0.06) and sham (p=0.06), indicating that the observed cardiorespiratory changes are likely due in part to changes in the response of nTS neurons. These data show that chronic decreases in afferent input via vagotomy reduce nTS somal activation in response to afferent stimulation, which likely modifies cardiorespiratory output. The mechanisms mediating these effects are currently under investigation. Missouri Comparative Medicine Program (T32 OD011126), National Heart, Lung, and Blood Institute (R01 HL132836, R01 HL128454, R01 HL 098602) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.