Photostimulation of caudal C1 catecholaminergic neurons reduces arterial pressure and heart rate

Caudal C1 catecholaminergic neurons in the ventrolateral medulla (VLM) between ~13.5 – 14 mm caudal to bregma were infected with a lentiviral‐vector containing channelrhodopsin‐2 and mCherry, under the control of the Phox2‐responsive promoter PRSx8. Immunohistochemical localization of mCherry in the efferent fibers and terminals of these C1 neurons demonstrates projections to the rostral raphe pallidus (rRPa), the nucleus tractus solitarius, the rostral VLM, the hypothalamus (including the PVH and DMH) and the preoptic area. In urethane/chloralose anesthetized rats (n=5) photostimulation (473nm, 10ms, 8–15mW) of these C1 neurons decreased mean arterial pressure (MAP) and heart rate in a laser pulse frequency‐dependent manner, with 40Hz stimulation producing a maximal depressor responses of −21 ± 6 mmHg and a bradycardia of −111 ± 7 bpm. The decrease in MAP was attenuated by nanoinjection of idazoxan (IDZ, 6nmol in 100 nl), in the rRPa (post‐IDZ, 40Hz: −6 ± 4 mmHg), whereas the bradycardia was not affected by idazoxan in the rRPa (post‐IDZ, 40Hz: −108 ± 25 bpm). The depressor response to activation of caudal C1 neurons may have arisen from activation of alpha2 receptors in rRPa leading to inhibition of cutaneous vasoconstriction and a reduction in total peripheral resistance. However, the role of other projection targets of caudal C1 neurons in the evoked depressor response and bradycardia are being explored. Supported by: NIH grants NS040987 (Shaun F. Morrison), DK082558 (CJM) and an American Heart Association Scientist Development Grant (CJM).