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, 103 (3), 332-336

C1 Neurons: A Nodal Point for Stress?


C1 Neurons: A Nodal Point for Stress?

Ruth L Stornetta et al. Exp Physiol.


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.

Keywords: anti-inflammatory reflex; autonomic nervous system; cardiovascular homeostasis.

Conflict of interest statement

Additional information:

Competing interests: the authors have no conflicts of interest.


A. C1 cells control both divisions of the autonomic nervous system via direct connections with preganglionic neurons. C1 cells also regulate the hypothalamo-pituitary axis (HPA) via direct connection to the paraventricular nucleus (PVH). The autonomic nervous system and the HPA can probably be affected by the C1 cells via more complex routes. B. Bulbospinal C1 cells and C1 cells with hypothalamic projections have collaterals that target a common set of brain structures, notably the dorsal vagal complex (NTS &/or DMV), PBN, PAG and noradrenergic neurons including the locus coeruleus. C. Schematic illustration of how the same C1 neurons might buffer BP changes and be responsible for hypertension and arousal. Rostral C1 neurons receive excitatory input from cardiopulmonary afferents such as those innervating the carotid bodies and inhibitory input from arterial and low-pressure baroreceptors. Activation of the latter inhibit C1 cells via a GABAergic relay located more caudally with the ventrolateral medulla (CVLM). Direct optogenetic stimulation of the C1 cells may cause arousal from sleep via the depicted C1 cell collaterals. D. This diagram illustrates how C1 cell activation by such diverse stimuli as restraint stress, infection, acupuncture, vagal afferent stimulation (vagal trunk and auricular nerve) might be able to reduce inflammation. Two efferent routes converging on catecholaminergic neurons located within prevertebral ganglia are postulated, one via vagal efferent neurons (Pavlov & Tracey, 2015) and the other via sympathetic preganglionic neurons (Martelli et al., 2014a; Abe et al., 2017).

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