C1 Neurons: The Body's EMTs

Guyenet, Patrice G., et al. "C1 neurons: the body's EMTs." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 305.3 (2013): R187-R204. Definition: C1 neurons commonly thought of as the body’s emergency medical technicians, are defined as neurons containing phenylethanolamine N-Methyl transferase (PNMT). The enzyme PNMT is allows for the production of the catecholamine epinephrine from norepinephrine. The majority of C1 neurons also have the enzymes tyrosine hydroxylase and dopamine β-hydroxylase as well which allows for the synthesis for norepinephrine and dopamine. Presently, it is suspected that most C1 neurons are clustered in the ventrolateral medulla (VLM), however the VLM also contains A1 neurons (catecholaminergic neurons that do not make PNMT). C1 neurons have projections to a variety of areas that largely play a role in autonomic responses or stress behaviors. Although C1 neurons are classified as catecholaminergic, there is no direct evidence of catecholamine release to intended targets. Instead, most C1’s are thought to use glutamatergic signaling transmission mainly through the use of vesicular glutamate transporter 2. There is also evidence to show the release of certain neuropeptides along with glutamate including TRH, Substance P, NPY and Enkephalin to produce a greater variety of excitatory and or inhibitory effects. About one third of all C1 neurons are located specifically in the rostral ventrolateral medulla (RVLM) and target sympathetic pre-ganglionic neurons. This region is referred to as the “pressor” region due to the fact that excitation of these neurons with glutamate leads to an increase in arterial blood pressure via vasoconstriction and cardimotor output. It is thought then that the responsibility of these C1 neurons within the RVLM is to maintain arterial blood pressure on a second to second basis. Regulation of these tonic neurons comes from another region in the VLM called the intermediate VLM (CVLM) that contains GABAergic neurons, and is meditated by a mechanism known as the baroreflex. It was also found that non-C1 neurons also reside in the RVLM, but their exact function is unknown. Interestingly, it was found that if the majority of C1 neurons are killed off using anti-DβH-saporin only a 10 mmHg change in arterial blood pressure is witnessed. Factors that could potentially account for this are compensation with non-C1 neurons, volume expansion of the kidney, baroreflex compensation, or peripheral catecholaminergic receptor supersensitivity. Other autonomic/stressor responses C1 neurons have been linked to include hypoxia, the CRH-ACTH-Corticosterone Cascade, the glucoprivic responses, as well as some parasympathetic sympathetic responses. Although it is thought that C1 neurons contribute to homeostatic regulation under a variety of physiological conditions, there are still many questions and functions yet to be discovered and understood. ~JI