Vagus nerve stimulation is differently integrated at the nucleus of the solitary tract (NTS) neurons during heart failure in rats
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
44
Name of Project's Faculty Sponsor
Eric Beaumont
Faculty Sponsor's Department
Biomedical Sciences
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
Vagus nerve stimulation (VNS) therapy is currently used to treat heart failure (HF) with reduced ejection fraction (HFrEF). VNS is typically used at a frequency of 5 Hz with an intensity that is sufficient to induce a slight bradycardia during stimulation. We previously shown that all myelinated and none of the unmyelinated afferents are activated during VNS. The current study investigates the integration of vagal afferents on NTS neurons in control and HF rats (ejection fraction < 60%) following different VNS protocols. Sprague-Dawley rats with pressure overload underwent a thoracic aortic constriction twelve weeks prior to terminal electrophysiology experiments and were compared to healthy controls. For terminal patch clamp experiments, the brainstem was removed under isoflurane anesthesia and a horizontal brainstem slice containing the solitary tract (ST) and medial NTS was obtained. Brain slice was maintained in physiological CSF and whole-cell voltage-clamp recordings was performed. Electrical shocks to the ST produced fixed latency evoked excitatory postsynaptic currents (eEPSCs) with a jitter < 200usec that identified NTS neurons with monosynaptic afferent input. EPSCs with jitter > 200usec were considered polysynaptic. ST stimulation protocols were used to mimic in vivo VNS using the following protocols: 1) continuous 1 Hz stimulation for 14 secs, 2) continuous 5 Hz stimulation for 14 secs, 3) continuous 20 Hz stimulation for 14 secs, 4) 300Hz burst stimulation (7 pulses) for 14 secs, IBI of 1 sec. Results showed that frequency and amplitude of spontaneous EPSCs from second-order neurons in HF rats were not different compared to sEPSCs observed control rats. 50 Hz stimulation protocol showed that HF rats present reduced amplitude of eEPSC and attenuated frequency-dependent depression. HF NTS neurons exhibit lower frequency of asynchronous EPSC compared to control (p < 0.05). VNS stimulations at 1Hz, 5Hz, 20 Hz elicited a decrease in evoked EPSC amplitude in NTS second-order neurons receiving C type afferent fibers in HF rats compared to control group (p < 0.05). 300 Hz with 7 pulses stimulation protocol failed to show any difference between control and HF neurons, either receiving C or A afferent terminals. In conclusion, second-order NTS neurons receiving C afferent vagal neurons in HF rats showed significantly reduced synaptic features compared to controls. Since VNS therapy is beneficial in improving cardiac function, its effect may rely on restoration of synaptic properties for central integration of vagal afferents at the NTS level.
Vagus nerve stimulation is differently integrated at the nucleus of the solitary tract (NTS) neurons during heart failure in rats
D.P. Culp Center Ballroom
Vagus nerve stimulation (VNS) therapy is currently used to treat heart failure (HF) with reduced ejection fraction (HFrEF). VNS is typically used at a frequency of 5 Hz with an intensity that is sufficient to induce a slight bradycardia during stimulation. We previously shown that all myelinated and none of the unmyelinated afferents are activated during VNS. The current study investigates the integration of vagal afferents on NTS neurons in control and HF rats (ejection fraction < 60%) following different VNS protocols. Sprague-Dawley rats with pressure overload underwent a thoracic aortic constriction twelve weeks prior to terminal electrophysiology experiments and were compared to healthy controls. For terminal patch clamp experiments, the brainstem was removed under isoflurane anesthesia and a horizontal brainstem slice containing the solitary tract (ST) and medial NTS was obtained. Brain slice was maintained in physiological CSF and whole-cell voltage-clamp recordings was performed. Electrical shocks to the ST produced fixed latency evoked excitatory postsynaptic currents (eEPSCs) with a jitter < 200usec that identified NTS neurons with monosynaptic afferent input. EPSCs with jitter > 200usec were considered polysynaptic. ST stimulation protocols were used to mimic in vivo VNS using the following protocols: 1) continuous 1 Hz stimulation for 14 secs, 2) continuous 5 Hz stimulation for 14 secs, 3) continuous 20 Hz stimulation for 14 secs, 4) 300Hz burst stimulation (7 pulses) for 14 secs, IBI of 1 sec. Results showed that frequency and amplitude of spontaneous EPSCs from second-order neurons in HF rats were not different compared to sEPSCs observed control rats. 50 Hz stimulation protocol showed that HF rats present reduced amplitude of eEPSC and attenuated frequency-dependent depression. HF NTS neurons exhibit lower frequency of asynchronous EPSC compared to control (p < 0.05). VNS stimulations at 1Hz, 5Hz, 20 Hz elicited a decrease in evoked EPSC amplitude in NTS second-order neurons receiving C type afferent fibers in HF rats compared to control group (p < 0.05). 300 Hz with 7 pulses stimulation protocol failed to show any difference between control and HF neurons, either receiving C or A afferent terminals. In conclusion, second-order NTS neurons receiving C afferent vagal neurons in HF rats showed significantly reduced synaptic features compared to controls. Since VNS therapy is beneficial in improving cardiac function, its effect may rely on restoration of synaptic properties for central integration of vagal afferents at the NTS level.