C1 neurons: a nodal point for stress?

Abstract

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.

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?

“…Central-mediated stress responses influence splenic immune functions by direct sympathetic innervation of lymphoid tissue and via hormones that enter the bloodstream [ 86 , 87 , 88 , 89 ]. Sympathetic nerves distribute to immune compartments in the spleen, and manipulation of the splenic nerve or its activity alters splenic immune responses, as well as distant localized and systemic inflammation.…”

VLM catecholaminergic neurons control tumor growth by regulating CD8 + T cells

“…How tumors communicate with the VLM CA neurons in the brain and how the neuronal activity of VLM CA neurons influence the adaptive immune system are not currently known. However, unlike the previously characterized direct innervation of tumors or immune-related organs by sympathetic or parasympathetic nerve fibers, the relationship(s) between VLM CA neurons and tumors and/or the immune system must be indirect, since the projection of these neurons does not go into peripheral tissues (3,(9)(10)(11). It is thus interesting to speculate that the cancer-related VLM CA neuronal function may be mediated by neuron-derived "factors" that 1) are able to cross the blood brain barrier and can be perceived by the adaptive immune system and/or tumor cells, or 2) the CA neuron projection can be relayed to the adaptive immune system and/or tumor tissues by secondary neurons.…”

Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats

“…Autonomic imbalance is commonly observed in patients with HF and is thought to play a major role in HF progression (Triposkiadis et al 2009). RVLM-C1 neurones can exert direct control over sympathetic activity through projections to preganglionic neurones and indirect control through projections to neurones that regulate breathing, arousal and stress (for review see Guyenet et al 2013;Stornetta & Guyenet, 2017). Hyperactivity of RVLM-C1 neurones contributes to increases in sympathetic tone associated with sleep-disordered breathing and cardiovascular disease (i.e.…”