Details

Autor(en) / Beteiligte

• Hofmann, Gabrielle C.
• Gama de Barcellos Filho, Procopio
• Khodadadi, Fateme
• Ostrowski, Daniela
• Kline, David D.
• Hasser, Eileen M.

Titel

Vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via pre‐ and postsynaptic effects in the nucleus tractus solitarii

Ist Teil von

• The Journal of physiology, 2024-03, Vol.602 (6), p.1147-1174

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Viscerosensory information travels to the brain via vagal afferents, where it is first integrated within the brainstem nucleus tractus solitarii (nTS), a critical 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 and reduces sighs during hypoxia. 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 weeks old) underwent right cervical vagotomy caudal to the nodose ganglion, or sham surgery. After 1 week, rats were anaesthetized, ventilated and instrumented to measure mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Vagal afferent stimulation (2–50 Hz) decreased cardiorespiratory parameters and increased neuronal Ca2+ measured by in vivo photometry and in vitro slice imaging of nTS GCaMP8m. Vagotomy attenuated both these reflex and neuronal Ca2+ responses compared to shams. Vagotomy also reduced presynaptic Ca2+ responses to stimulation (Cal‐520 imaging) in the nTS slice. The decrease in HR, SSNA and PhrNA due to nTS nanoinjection of exogenous glutamate also was tempered following vagotomy. This effect was not restored by blocking excitatory amino acid transporters. However, the blunted responses were mimicked by NMDA, not AMPA, nanoinjection and were associated with reduced NR1 subunits in the nTS. Altogether, these results demonstrate that vagotomy induces multiple changes within the nTS tripartite synapse that influence cardiorespiratory reflex responses to afferent stimulation. Key points Multiple mechanisms within the nucleus tractus solitarii (nTS) contribute to functional changes following vagal nerve transection. Vagotomy results in reduced cardiorespiratory reflex responses to vagal afferent stimulation and nTS glutamate nanoinjection. Blunted responses occur via reduced presynaptic Ca2+ activation and attenuated NMDA receptor expression and function, leading to a reduction in nTS neuronal activation. These results provide insight into the control of autonomic and respiratory function, as well as the plasticity that can occur in response to nerve damage and cardiorespiratory disease. figure legend Vagotomy blunts cardiorespiratory responses to afferent stimulation through multiple mechanisms. Seven days following unilateral vagotomy, vagal afferent stimulation produced blunted sympathetic and phrenic nerve responses compared to shams (left). Vagotomy also attenuated Ca2+ responses to afferent stimulation in nTS somas (left) and terminals (top right) in vivo and in vitro. Following vagotomy, nTS injection of glutamate agonists (glutamate and NMDA) also produced blunted cardiorespiratory responses and reduced expression of NMDA receptor subunit NR1 in the nTS (middle right). We propose that the reduced responses to vagal afferent stimulation following vagotomy are a result of decreased presynaptic glutamate release from vagal afferent terminals and reduced NMDA receptor expression and function on postsynaptic nTS neurons (bottom right). Nucleus tractus solitarii (nTS), mean arterial pressure (MAP), sympathetic nerve activity (SNA), phrenic nerve activity (PhrNA).