Locus coeruleus: its anatomy, functions and diseases.

Also known as the locus ceruleus, this nucleus of the brain is related to emotions.

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

Within it we can find a whole range of structures without which we would not be able to do practically anything, nor respond to external stimuli or interact with the environment. One of these structures is the locus coeruleusa nucleus located in the brainstem, which we will discuss in this article.

What is the locus coeruleus?

The locus coeruleus (LC), also known as the locus ceruleus or locus caeruleusis a nucleus composed mainly of noradrenergic neurons located in the pons of the brainstem. 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 the brain stem. related to the physiological responses of stress and fear..

In fact, the locus coerulus is considered to be one of the parts of the reticular system, which is a network of interconnected neurons scattered mainly throughout the brainstem and projecting to the cerebral cortex; its functions are related to the regulation of levels of consciousness and psychological arousal.

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

The corresponding connections and circuits between the locus coeruleus and the neocortex, diencephalon, limbic system and spinal cord highlight its 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 neuronal population, which contributes to the cognitive deterioration of the person and to the appearance of a whole series of disorders. the onset of a variety of neurological disorders..

This center of the nervous system was discovered in 1784 by the French physician and anatomist Félix 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 the year 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 pons of the brainstem, more specifically in the lateral part of the fourth ventricle of the brain. This structure is mainly made up of medium-sized neurons and is distinguished by its and is distinguished by harboring melanin granules within its neurons, which give it its characteristic blue coloration.

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

Regarding the connections of the locus coeruleus, this has projections to virtually 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 innervating nucleus since the norepinephrine in it has excitatory effects on most of the brain; mediating excitation and prompting brain neurons to be activated by stimuli.

In addition, because of its important function as a homeostatic control center in the organism, the LC also receives afferent fibers coming from the hypothalamus.. Likewise, the cingulate gyrus and amygdala also innervate the locus coeruleus, allowing emotional distress and pain, and stimuli or stressors to trigger noradrenergic responses.

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

What are the functions of this brain region?

Due to the increased production of noradrenaline, the main functions of the nucleus coeruleus are those related to the effects that the sympathetic nervous system exerts on stress and fear responses. In addition, recent research also points to the possibility that this brainstem center is of vital importance in the proper functioning of vigilance processes. the correct functioning of the processes of wakefulness.

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

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

• Arousal 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 disturbances such as clinical depression, panic disorder, anxiety, Parkinson's and Alzheimer's diseases.

In addition, there are a large number of mental or psychological disturbances which appear as a result of a series of alterations in the norepinephrine modulatory neurocircuitry.. Among them we find disorders of affect and anxiety, Post Traumatic Stress Disorder (PTSD) or Attention Deficit Hyperactivity Disorder (ADHD). In all of them there are alterations in the level of activation of the nervous system (which is not surprising, considering that the locus coerulus is part of the reticular system).

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 locus coeruleus dysregulation.

Finally, one of the most novel and surprising findings is one that suggests a relationship between dysregulation of locus coeruleus function and autism.. This research suggests that the locus coeruleus and noradrenergic systems are dysregulated by an interplay of environmental, genetic and epigenetic factors. And that, in addition, the effects of anxiety and stress states may also disorganize these systems, especially in the later stages of prenatal development.

Bibliographic references:

• Maeda, T. (2000). The locus coeruleus: history. Journal of Chemical Neuroanatomy, 18(1–2): pp. 57 - 64.
• Mouton, P.R., Pakkenberg, B., Gundersen, H.J.; Price, D.L. (1994). Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals. Journal of Chemical Neuroanatomy, 7(3): pp. 185 - 190.
• Taneja P.; Ogier M.: Brooks-Harris, G.; Schmid, D.A.; Katz, D.M.; Nelson, S.B. (2009). Pathophysiology of Locus Ceruleus Neurons in a Mouse Model of Rett Syndrome. Journal of Neuroscience. 29(39): pp. 12187 - 12195.