Locus ceruleus

The locus ceruleus is a structure located on the floor of the fourth ventricle in the rostral pons. It contains more than 50% of all noradrenergic neurons in the brain, and projects to almost all areas of the central nervous system. 

Locus ceruleus Nucleus of norepinephrine-containing neurons located in the brain stem that are responsible for physiologic response to stress and panic. 

Cirelli, C. Tononi, G. (2004). Locus ceruleus control of state-dependent gene expression./. Neurosci 24, 5410-19. 

Locus ceruleus Vigilance, sleep/wake cycle... 

The answers are 318-d, 319-c, 320-a. (Hardman, pp 120-1220 Norepinephrine is synthesized from dopamine by dopamine-p-oxidase, which hydnoxylates the p-carbon This enzyme is localized in the amine storage granules. Norepinephrine is found in adrenergic fibers, the adrenal medulla, and in neurons in the locus ceruleus and lateral ventral tegmental fields of the CNS. 

Six groups of cell bodies of noradrenergic neurons are clustered in the medulla oblongata, pons and midbrain. They are considered part of the reticular formation and extend from the spinal cord to the lateral pontine reticular formation. One of the best-studied of these groups is the locus ceruleus (Fig. 12-5), which has many ascending and descending projections from the pons. 

Distribution Pancreas, small intestine, locus ceruleus, hippocampus Liver, thalamus Heart, lung, aorta, hippocampus, olfactory bulb... 

The noradrenergic neurons of the locus ceruleus have provided a useful model system for the study of opiate addiction (see Ch. 56). Acutely, opiates inhibit these neurons, in part by inhibiting the cAMP pathway via inhibition of adenylyl cyclase. Chronically, these neurons become tolerant to opiates that is, their firing rates recover toward normal levels with continued exposure to the... 

Increasing evidence indicates that a chronic opiate-induced upregulation of the cAMP pathway, manifested by increased concentrations of adenylyl cyclase, PKA and several phosphoprotein substrates for the protein kinase, contributes to opiate tolerance, dependence and withdrawal exhibited by locus ceruleus neurons [66]. This upregulated cAMP pathway can be viewed as a homeostatic response of the neurons to persistent opiate inhibition of the cells. In the chronic opiate-treated state, the upregulated cAMP pathway helps return neuronal firing rates to control levels, i.e. tolerance. Upon abrupt removal of the opiate via the administration of an opiate receptor antagonist, the upregulated cAMP accounts for part of the withdrawal activation of the cells. 

Chronic opiate-induced upregulation of the cAMP pathway appears to be mediated in part by CREB chronic opiate administration increases CREB expression mice deficient in CREB show attenuated physical opiate dependence and withdrawal and selective reductions of CREB in the locus ceruleus prevent upregulation of specific components of the cAMP pathway in response to chronic opiate administration [66]. This latter action is associated with attenuation of the electrical excitability of locus ceruleus neurons and of physical opiate dependence and withdrawal. 

LC locus ceruleus MSUD maple syrup urine disease... 

Serotonergic neurons of the raphe nuclei and noradrenergic cells of the locus ceruleus are lost... 

Curtis AL, Pavcovich LA, Valentino RJ (1999) Long-term regitiation of locus ceruleus sensitivity to corticotropin-releasing factor by swim stress. J Pharmacol Exp Ther 289 1211-1219... 

Most central noradrenergic neurons are located in the nucleus locus ceruleus of the pons and in neurons of the reticular formation. Fibers from these nuclei innervate a large number of cortical, subcortical, and spino-medullary fields. Many functions have been ascribed to the central noradrenergic neurons, including a role in... 

Mechanism of Action Although its exact mechanism of action is unknown, this non-barbiturate is thought to bind to serotonin and dopamine receptors in the CNS. The drug may also increase norepinephrine metabolism in the locus ceruleus. Therapeutic Effect Decreased anxiety... 

About half of all noradrenergic neurons, i.e., 12,000 on each side of the brain stem, are located in the locus ceruleus (LC). They provide the extensive noradrenergic innervation of cortex, hippocampus, thalamus, cerebellum, and spinal chord. The remaining neurons are distributed in the tegmental region. They innervate predominantly the hypothalamus, basal forebrain, and spinal chord. 

Our cerebrospinal fluid (CSF) observations and. . . studies of the locus ceruleus (LC) and clonidine call for the assessment of noradrenergic metabolism and clonidine in Tourette s syndrome. 

By activating presynaptic autoreceptors in brain stem locus ceruleus neurons (where most noradrenergic fibers have their origin), clonidine reduces norepine-pherine release and turnover. This inhibitory effect on noradrenergic locus ceruleus neurons, as well as direct effects on thalamic receptors, are most likely responsible for the sedative effects of clonidine (Berridge and Foote, 1991 Buzsaki et ah, 1991). 

---