Locus coeruleus: its anatomy, functions and diseases

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

Within that, we can find a whole range of structures without which we could hardly do anything, 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 that we will talk about throughout this article.

    What is the locus coeruleus?

    The locus coeruleus (LC), also known as the locus coeruleus or locus caeruleus, is a nucleus composed mainly of noradrenergic neurons located in the protuberance of the brainstem. This center is one of the parts belonging to the reticular activation system and its main functions are those linked 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 connected to each other and scattered mainly through the brainstem and projecting into the cortex. its functions concern the regulation of levels of consciousness and psychological activation.

    In addition, the locus coeruleus provides the main source of norepinephrine (Or norepinephrine, NE) throughout the brain, brainstem, cerebellum, and spinal cord. Its neuronal activity plays an essential role in the integration of sensory information in the regulation of activation, attention and certain functions of memory.

    The connections and corresponding circuits between the locus coeruleus and the neoscort, the diencephalon, the limbic system and the spinal cord underline its importance in the functioning of the neural axis.

    Due to the aging of the person or certain diseases, the locus coeruleus can suffer significant losses to the neuronal population, which contributes to the cognitive impairment 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 some time later, the German psychiatrist Christian Reil redefined it in a more concrete and specific way. However, it was not until 1812 that he received the name which remains to this day, which was given to him by his brothers Joseph Wenzel and Karl Wenzel.

    LC Anatomy and Connections

    The specific location of the locus coeruleus is in the posterior area of ​​the brainstem protrusion, more specifically in the lateral part of the ventricular chamber of the brain. this structure it is mainly made up of medium-sized neurons and is distinguished by the accommodation of melanin granules in its neurons, which gives it its characteristic blue coloration.

    In an adult human, a healthy locus coeruleus can be made up of between 22.00 and 51,000 pigmented neurons which can vary in size to the point that the larger one doubles in volume to the rest.

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

    We refer to the locus coeruleus as an innervating nucleus because the norepinephrine it contains has excitatory effects on most of the brain; by excitation and by stimulating brain neurons to be activated by stimuli.

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

    Finally, the cerebellum and the afferents of the raft nuclei also send projections to the locus coeruleus, in particular the nucleus of the pontis raft and the nucleus of the dorsal chevron.

    What are the functions of this brain region?

    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 has on stress and fear responses. In addition, recent research also indicates the possibility that this brainstem center is vitally important in the proper functioning of the vigil process.

    Likewise, other studies link the locus coeruleus to PTSD. as well as with the pathophysiology of dementias, Which are linked by the loss of noradrenergic stimulus.

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

    • Excitation 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 function of the locus coeruleus has been associated with a large number of mental disorders and disorders such as clinical depression, panic disorder, anxiety, and Parkinson’s and Alzheimer’s disease.

    In addition, there are a large number of mental or psychological disorders that appear as a result of a number of alterations in the neurocircuits modulating norepinephrine. These include affective and anxiety disorders, post-traumatic stress disorder (PTSD), and 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, given that the locus coerulus is part of the reticular system).

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

    Finally, one of the most recent and surprising discoveries is that which suggests a relationship between a disruption 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 interrelation of environmental, genetic and epigenetic factors. And that in addition, the effects of anxiety and stressful states can also disrupt these systems, especially in the later stages of prenatal development.

    Bibliographical references:

    • Maeda, T. (2000). The locus coeruleus: history. Journal of Chemical Neuroanatomy, 18 (1-2): pages 57-64.
    • Sheep, PR, Pakkenberg, B., Gundersen, HJ; Price, DL (1994). Absolute number and size of pigmented neurons at locus coeruleus in young and old individuals. Journal of Chemical Neuroanatomy, 7 (3): pages 185-190.
    • Taneja P .; Ogier M .: Brooks-Harris, G .; Schmid, DA; Katz, DM; Nelson, SB (2009). Pathophysiology of Locus Ceruleus neurons in a mouse model of Rett syndrome. Journal of Neuroscience. 29 (39): pages 12187 to 12195.

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