Locus coeruleus: its anatomy, functions and diseases

The whole of the human organism houses within it a whole series of structures and internal nuclei whose functions and tasks involve a level of complexity that still amazes the medical community and scientific 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 not carry out practically nothing, as well as not responding to external stimuli or interacting with the environment. One of these structures is the locus coeruleus, a nucleus located in the brainstem and which we will talk about throughout this article.

• Related article: "Parts of the human brain (and functions)"

What is the locus coeruleus?

The locus coeruleus (LC), also known as the locus cerulean or locus caeruleus, is a nucleus composed mainly of noradrenergic neurons found in the pons of the brainstem. This center of is one of the parts belonging to the reticular activation system and its main functions are those related to physiological responses to 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 neurons. interconnected and spread primarily through the brainstem and projecting into the cortex cerebral; its functions have to do with the regulation of levels of consciousness and psychological activation.

Furthermore, the locus coeruleus provides the main source of norepinephrine (or norepinephrine, NE) for the entire brain, brainstem, cerebellum and the spinal cord. The neuronal activity of this exerts an essential role in the integration of sensory information when regulating activation, attention and certain memory functions.

Connections and corresponding circuits between the locus coeruleus and the neocortex, diencephalon, limbic system and the spinal cord highlights its importance within the functioning of the neural axis.

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

This center of the nervous system was discovered in 1784 by the French physician and anatomist Félix Vicq-d’Azyr, and later the German psychiatrist Christian Reil, redefined it in a more concrete and specific. However, it was not until 1812 when it received the name that remains to this day, which was given to it by brothers Joseph Wenzel and Karl Wenzel.

LC anatomy and connections

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 consists mainly of medium-sized neurons and it 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 be made up of between 22,000 and 51,000 neurons pigmented of which can vary in size to the point that the largest double in volume when rest.

Regarding the connections of the locus coeruleus, this has projections to practically any area of ​​the nervous system. Some of these connections include its conservative role in the spinal cord, brainstem, cerebellum, and brain. hypothalamus, or to the nuclei of thalamic transmission, the amygdala, the basal telencephalon and the cortex.

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

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

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

What functions does this brain region perform?

Due to the increased production of norepinephrine, 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 brain stem center is of vital importance in the correct functioning of waking processes.

In the same way, other studies link the locus coeruleus with the Post Traumatic Stress Disorder (PTSD), as well as the pathophysiology 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:

• 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

The abnormal or pathological functioning of the locus coeruleus has been associated with a large number of disorders and mental disorders such as clinical depression, panic disorder, anxiety, and illness from Parkinson's Y Alzheimer's.

In addition, there are a large number of mental or psychological alterations which appear as a consequence to a series of alterations in norepinephrine modulating neurocircuits. Among them we find affect and anxiety disorders, Post-Traumatic Stress Disorder (PTSD) or the Attention deficit disorder and hyperactivity (ADHD). In all of them there are alterations in terms of the level of activation of the nervous system (something that is not surprising, considering that the locus coerulus is part of the reticular system).

In addition, it is speculated that certain medications such as norepinephrine reuptake inhibitors, Serotonin-norepinephrine and norepinephrine-dopamine reuptake inhibitors can 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 dysregulation of the functioning of the locus coeruleus and autism. These investigations suggest that the locus coeruleus system and the noradrenergic system are deregulated by an interplay of environmental, genetic, and epigenetic factors. And that, in addition, the effects of anxiety and stress states can also disorganize these systems, especially in the last 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.