Acute Intermittent Optogenetic Stimulation of Median Preoptic Nucleus (MnPO) Induces Sympathetic Long-term Facilitation (sLTF)

Acute intermittent hypoxia can produce a ramp increase in sympathetic nerve activity (SNA). The induction of this increase, termed sympathetic long-term facilitation (sLTF), involves the paraventricular nucleus (PVN). The median preoptic nucleus (MnPO) projects to the PVN and might mediate the induction of sLTF. This study used an intersectional viral approach to test the ability of acute intermittent optogenetic (AIO) stimulation of PVN-projecting MnPO neurons to induce sLTF. Male Sprague-Dawley rats were microinjected with CRE-containing retrograde-AAV in PVN and with either Channelrhodopsin 2-containing AAV or control virus in MnPO. This resulted in CRE-dependent expression of either ChR2 or mCherry in MnPO-PVN neurons. Following a 4-wk recovery, rats underwent AIO experiments where SNA, blood pressure (BP), and heart rate (HR) were recorded under anesthesia. MnPO terminals in the PVN were stimulated with a train of 5 Hz stimuli. A single optogenetic duty cycle did not alter splanchnic SNA, renal SNA, blood pressure, nor heart rate. AIO significantly increased splanchnic SNA (P=0.0163) in rats with ChR2 as compared to rats injected with the control vector 1h post-AIO. There were no differences in renal SNA, BP, and between rats injected with ChR2 as compared to those injected with the control vector 1h post-AIO. These results suggest that intermittent activation of PVN-projecting MnPO neurons may induce sLTF in the splanchnic SNA but not in renal SNA. Further study is needed to clarify the mechanisms responsible for the differential effects of MnPO-PVN AIO.