Acute intermittent optogenetic stimulation of glutamatergic NTS neurons induces sympathetic long‐term facilitation

Abstract

Acute intermittent hypoxia (AIH) induces phrenic and sympathetic long‐term facilitation (LTF). Phrenic LTF can be induced by carotid sinus nerve stimulation, suggesting that hypoxia is not necessary to generate phrenic LTF. To determine if hypoxia is necessary to generate sympathetic LTF, we investigated the effect of acute intermittent optogenetic stimulation (AIO) of glutamatergic NTS neurons on renal sympathetic nerve activity (RSNA) in isoflurane anesthetized, vagotomized and artificially ventilated Sprague‐Dawley rats. AIH was performed by ventilation with 10% oxygen for 1min every 6min for a total of 10 exposures to hypoxia. In a separate group of animals, AAV containing CaMKIIa ‐ hChR2(H134R) ‐ mCherry was injected into NTS to express channelrhodopsin2 in glutamatergic neurons and the same pattern of stimulation as in the AIH protocol was used to stimulate the NTS (20 Hz, 5ms duration and 600mA for 1min every 6min for a total of 10 stimuli). Arterial Pressure (AP), RSNA and heart rate (HR) were compared at baseline (before) and 60min after AIH (n=6) or AIO (n=2). AIH increased AP and HR (P<0.05). RSNA was increased by 85% measured 60min after AIH (P=0.02). AIO increased AP and HR. RSNA similarly increased by 60% measured 60min after AIO. These results suggest that acute intermittent direct stimulation of glutamatergic NTS neurons can induce sympathetic LTF in the absence of hypoxia. Supported by HL‐088052