C1 neurons: a nodal point for stress?

NEW FINDINGS: What is the topic of this review? The C1 neurons (C1) innervate sympathetic and parasympathetic preganglionic neurons plus numerous brain nuclei implicated in stress, arousal and autonomic regulations. We consider here the contribution of C1 to stress-induced responses. What advances does it highlight? C1 activation is required for blood pressure stability during hypoxia and mild hemorrhage which exemplifies their homeostatic function. During restraint stress, C1 activate the splenic anti-inflammatory pathway resulting in tissue protection against ischemic injury. This effect, along with glucose release and, possibly, arousal are examples of adaptive non-homeostatic responses to stress that are also mediated by C1. The C1 cells are catecholaminergic and glutamatergic neurons located in the rostral ventrolateral medulla. Collectively, these neurons innervate sympathetic and parasympathetic preganglionic neurons, the hypothalamic paraventricular nucleus and countless brain structures involved in autonomic regulation, arousal and stress. Optogenetic inhibition of rostral C1 neurons has little effect on blood pressure (BP) at rest in conscious rats but produces large reductions in BP when the animals are anaesthetized or exposed to hypoxia. Optogenetic C1 stimulation increases BP and produces arousal from non-rapid eye movement sleep. C1 cell stimulation mimics the effect of restraint stress to attenuate kidney injury caused by renal ischaemia-reperfusion. These effects are mediated by the sympathetic nervous system through the spleen and eliminated by silencing the C1 neurons. These few examples illustrate that, depending on the nature of the stress, the C1 cells mediate adaptive responses of a homeostatic or allostatic nature.