Ethan Hunt! Your locus ceruleus is calling…

On a recent date night, my husband and I took in the latest Mission Impossible movie. “That Tom Cruise character,” I marveled, watching him shimmy up the tallest building in Dubai. “He’s definitely in sympathetic overdrive. Clearly a case of ANS imbalance.” My husband looked at me with a mixture of pity and admiration and called me a nerd, which I am, but that’s OK because he’s a scientist too. Here’s what’s on our minds these days at NeuroScience

As we mentioned in a recent post, all involuntary bodily functions are controlled by the autonomic nervous system (ANS). Because of its extensive influence, when the ANS is out of balance, it can cause a range of health issues affecting sleep, energy levels, metabolism, gastrointestinal function, cardiovascular function, psychiatric issues, and more, resulting in a wide variety of symptoms that may differ among patients based on genetic predisposition and other factors.

For this reason, many institutions have come to recognize and endorse the importance of ANS assessment, including the American Heart Association, American Diabetes Association, the National Institutes of Health, and others.

Neurocircuitry research has revealed that a dysregulated ANS can often be traced to alterations in key areas of the brain that are critical for maintaining properly balanced sympathetic (SNS) and parasympathetic (PNS) tone (we described the concept of tone in our earlier post). Investigations have shown that various disorders can be successfully addressed by targeting specific brain nuclei with rationally selected pharmacological interventions based on neurotransmitters and metabolite measurements in urine and blood (Lechin et al., 1996).

In other words, ANS imbalances, while impacting peripheral organ systems and tissues, are likely governed by central brain regions. The following examples describe two opposing profiles of ANS imbalance that can be measured in urinary neurotransmitters – and the hypothesized central causes in the brain.

  • Low urinary norepinephrine combined with elevated cortisol and epinephrine This imbalance may result from upregulated activity of specific brainstem regions including the serotonergic dorsal raphe (DR), noradrenergic locus coeruleus (LC), and adrenergic rostroventral lateral medulla (RVLM or C1). The C1 is known to trigger the release of epinephrine and cortisol from the adrenal glands into the circulation (Lechin & van der Dijs, 2008). Increased activity of C1 has an opposing effect on the noradrenergic A5 area.
  • Elevated urinary norepinephrine relative to cortisol and epinephrine
    This profile may be due to upregulated activity of the serotonergic median raphe  and noradrenergic A5, resulting in decreased activity of the locus ceruleus, RVLM, and DR. Neurons in the A5 area stimulate an increased release of  norepinephrine into the circulation and may also  decrease the release of epinephrine and cortisol  (Lechin & van der Dijs, 2008). Sound like adrenal fatigue to you?

The locus ceruleus (LC) is emerging as a very important master controller in our brainstem, because – through norepinephrine signals – it  regulates the C1 and A5 areas, which have opposing effects on SNS tone. It effectively acts as a fulcrum to keep the effects of A1 and C5  in balance.


The locus ceruleus (LC) uses norepinephrine to signal the regulation of the C1 and A5 areas, which have opposing effects on SNS tone.

When this ‘fulcrum’ is functioning suboptimally, ANS imbalances can result. In our next post, we’ll discuss some ideas for maintaining proper LC function. Which should be perfect if you’re Ethan Hunt and insist on scaling tall buildings without any ropes.

Could your ANS be in free fall?

Could your ANS be in free fall?

This entry was posted in Neurology and tagged . Bookmark the permalink.

2 Responses to Ethan Hunt! Your locus ceruleus is calling…

  1. Héctor Jara says:

    Very nice review about the work of my Teacher Fuad Lechín. I recomend you review our recently work in neuroprotection in:
    I want to use in a conference your grafic of the locus ceruleus imbalance. is the best!!!!

  2. steffani says:

    Thanks! I’m writing a paper on PTSD “prevention” drugs and this helped clarify some confusion I had regarding the use of hydrocortisol.

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