The human organism as a whole houses a whole series of structures and internal nuclei whose functions and tasks involve a level of complexity that still amazes the medical and scientific community. However, there is one system that stands out from the rest: the central nervous system.

Within this we can find a whole range of structures without which we could do practically nothing, nor respond to external stimuli or interact with the environment. One of these structures is the locus coeruleus , a nucleus located in the brain stem and which we will talk about throughout this article.

What is the locus coeruleus?

The locus coeruleus (LC), also known as the cerulean locus or locus caeruleus , is a nucleus composed primarily of noradrenergic neurons found in the bulge of the brain stem. This center is one of the parts belonging to the reticular activation system and its main functions are those related to the physiological responses of stress and fear .

In addition, the locus coeruleus provides the main source of noradrenaline (or norepinephrine, NE) for the entire brain, brain stem, cerebellum, and spinal cord. Its neural activity plays an essential role in the integration of sensory information in regulating activation, attention, and certain memory functions.

The corresponding connections and circuits between the locus coeruleus and the neocortex, the diencephalon, the limbic system and the spinal cord highlight their importance in the functioning of the neural axis.

Due to the aging of the person or to certain diseases, the locus coeruleus can suffer important losses in terms of the neuronal population, which contributes to the cognitive deterioration of the person and to the appearance of a whole series of neurological disorders .

This centre of the nervous system was discovered in 1784 by the French doctor and anatomist Felix Vicq-d’Azyr, and some time later the German psychiatrist Christian Reil redefined it in a more concrete and specific way. However, it was not until 1812 that it received the name that remains to this day, which was given to it by Brothers Joseph Wenzel and Karl Wenzel.

Anatomy and connections of the LC

The specific location of the locus coeruleus is in the posterior area of the brain stem bulge, more specifically in the lateral part of the fourth ventricle of the brain. This structure consists mainly of medium-sized neurons and is distinguished by the fact that it contains melanin granules within its neurons, which give it its characteristic blue colouring.

In an adult human, a healthy locus coeruleus can be formed by between 22,000 and 51,000 pigmented neurons of which the size can vary to the point that the largest ones are twice as large as the rest.

As for the connections of the locus coeruleus, it has projections towards practically any area of the nervous system . Some of these connections include the conservative function it performs in the spinal cord, brain stem, cerebellum and hypothalamus, or to the thalamic transmission nuclei, amygdala, basal telencephalon and cortex.

We refer to the locus coeruleus as an inervating nucleus since the norepinephrine that exists in it has excitatory effects on most of the brain; mediating the excitation and driving the brain neurons to be activated by stimuli.

Furthermore, due to its important function as a homeostatic control centre in the body, the LC also receives afferent fibres from the hypothalamus . Likewise, the cingulate gyrus and the amygdala also innervate the locus coeruleus, allowing emotional distress and pain, and stimuli or stressors to trigger noradrenergic responses.

Finally, the cerebellum and the afferents of the raphe nuclei also send projections towards the locus coeruleus, specifically the raphe pontis nucleus and the raphe dorsal nucleus.

What functions does this brain region perform?

Due to the increased production of noradrenaline, the main functions of the nucleus coeruleus are those related to the effects of the sympathetic nervous system on stress and fear responses. Furthermore, recent research also points to the possibility that this centre of the brain stem is of vital importance in the correct functioning of the waking processes .

In the same way, other studies link the locus coeruleus with Post-Traumatic Stress Disorder (PTSD), as well as with the physiopathology of dementias , which are related through the loss of the noradrenergic stimulus.

However, due to the large number of projections found in the LC, it has been linked to a large number of functions. Among the most important are

  • Excitement and sleep-wake cycles .
  • Attention and memory.
  • Behavioral flexibility, behavioral inhibition and psychological aspects of stress.
  • Cognitive control .
  • Emotions.
  • Neuroplasticity.
  • Postural control and balance .

Pathophysiology of this nucleus: associated disorders

Abnormal or pathological functioning of the locus coeruleus has been associated with a large number of mental disorders and alterations such as clinical depression, panic disorder, anxiety and Parkinson’s and Alzheimer’s diseases.

In addition, there are a large number of mental or psychological alterations which appear as a consequence of a series of alterations in the norepinephrine modulating neurocircuits . Among them we find affective and anxiety disorders, Post-Traumatic Stress Disorder (PTSD) or Attention Deficit and Hyperactivity Disorder (ADHD).

In addition, it is speculated that certain drugs such as norepinephrine reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and norepinephrine-dopamine reuptake inhibitors may be very effective in counteracting the effects of deregulation of the locus coeruleus.

Finally, one of the most novel and surprising discoveries is that which suggests a relationship between a deregulation of the functioning of the locus coeruleus and autism . This research suggests that the locus coeruleus system and the noradrenergic system are deregulated by an interrelationship of environmental, genetic and epigenetic factors. And that, in addition, the effects of states of anxiety and stress can also disrupt these systems, especially in the last stages of prenatal development.