C1 neurons: the body's EMTs

Abstract

The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. C1 neurons; blood pressure; brain stem BEST KNOWN for their contribution to the control of arterial pressure (AP), the C1 neurons have also been implicated in many other physiological processes ranging from neuroendocrine responses to infection and inflammation, glucose homeostasis, reproduction, breathing, thermoregulation, hypothalamo-pituitary axis (HPA)-mediated stress responses, and food consumption. The purpose of this review is to summarize the most salient information concerning the C1 cells, to point out some of the remaining gaps in our current knowledge, and to suggest a few unifying physiological principles that could account for these seemingly disparate observations. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, we propose that these neurons are, figuratively speaking, the body's "emergency medical technicians." By this we imply that these neurons produce stereotyped autonomic, metabolic, and neuroendocrine responses designed to help the organism survive major acute physical stresses such as accidental, pathological, or dive-related hypoxia or physical injury and its associated cohort of acute infection, blood loss, and hypotension. These emergency responses include, in the short term and depending on the stress, vasoconstriction, cardioinhibition, or acceleration, breathing stimulation, antidiuresis, changes in metabolism, and gastrointestinal (GI) functions designed to conserve pe...

Neurônios catecolaminérgicos do tronco encefálico participam dos ajustes respiratórios induzidos por hipóxia e hipercapnia.

“…A porção ventrolateral do bulbo (VLM) está localizada no quadrante ventrolateral da formação reticular bulbar, sendo delimitada, em sua porção rostral, pela porção caudal do núcleo motor do facial (VII) e, em sua porção caudal, pela porção compacta do núcleo ambíguos (NA) (Ilustração 1A) (Spyer, Gourine, 2009;Guyenet et al, 2013). O VLM é subdividido em três porções: rostral, intermediária e caudal, sendo, respectivamente, denominadas de bulbo ventrolateral rostral (RVLM), bulbo ventrolateral intermediário (IVLM) e bulbo ventrolateral caudal (CVLM).…”

“…O painel (B) apresenta um esquema representativo das etapas envolvidas na síntese das catecolaminas (Panei A: adaptado de Spyer, Gourine, 2009) No VLM, o grupamento C1 se localiza no RVLM e IVLM, sendo que, no RVLM, ele se inicia na porção caudal do núcleo motor do facial (-11,4 mm do bregma) e se estende até o final da porção compacta do núcleo ambíguos (-12,6 mm do bregma), enquanto no IVLM, ele se inicia no final da porção compacta do núcleo ambíguos (-12,6 mm do bregma) e termina no ponto médio da área postrema (-13,8 mm do bregma) . Os neurônios adrenérgicos C1 são, por definição, um dos três grupos de células do sistema nervoso central que sintetizam e expressam todas as enzimas necessárias para a síntese de adrenalina (Ilustração 1B), sendo a enzima Feniletanolamina-N-Metil transferase (PNMT), responsável pela conversão da noradrenalina em adrenalina, utilizada como marcador fenotípico deste grupamento neuronal Guyenet et al, 2013). Dentre os três grupamentos adrenérgicos: C1, C2 e C3, o C1 é o maior deles, contendo aproximadamente 70% dos neurônios adrenérgicos do sistema nervoso central (Minson et al, 1990;Comer et al, 199).…”

“…Com relação a estas conexões, está bem descrito na literatura que aproximadamente 70% dos neurônios do RVLM são neurônios C1 e que, destes, aproximadamente 70% se projetam para IML, de modo que os 30% restantes se projetam para o PVN (Milson et al, 1990;Schreihofer, Guyenet 1997;Card et al, 2006;Guyenet et al, 2013).…”

“…Os neurônios do grupamento catecolaminérgico C1, localizados na porção ventrolateral do bulbo (VLM), são classicamente conhecidos por seu envolvimento no controle cardiovascular Schreihofer, Guyenet, 1997;Madden et al, 1999;Guyenet et al, 2013). O modelo atual propõe que estes neurônios são, predominantemente, recrutados em situações que ofereçam risco de vida aos indivíduos, desencadeando respostas generalizadas e estereotipadas em defesa da homeostase .…”

Mecanismos purinérgicos no bulbo ventrolateral rostral modulam respostas cardiovasculares e respiratórias promovidas pela ativação dos quimiorreceptores centrais e periféricos.

“…Peripheral chemoreceptors of the carotid body sense changes in O 2 /CO 2 /H + and also regulate breathing and sympathetic outflow, via synapses through the central nervous system (Kumar & Prabhakar, 2012). It is well established that the rostral ventrolateral medulla (RVLM) contains two important subsets of neurons involved in cardiorespiratory control during the chemoreflexes, namely the CO 2 /H + -sensitive neurons of the retrotrapezoid nucleus (RTN) that function as central respiratory chemoreceptors and presympathetic catecholaminergic C1 neurons that control sympathetic vasomotor tone in response to a number of reflexes, including the peripheral chemoreflex Guyenet et al 2013).…”