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Locus Coeruleus


In normal brain, a specific interplay among the blood-brain barrier (BBB), substantia nigra (SN), and Locus coeruleus (LC) creates the condition for a self-accelerating damage to the SN.  

In the Locus coeruleus, neither a 2-day treatment with the tachykinin NK1 receptor antagonists [ (2S,3S)-cis-2-(diphenylmethyl)-N-[ (2-methoxyphenyl) methyl]-1-azabicyclo[ 2.2.2]octan-3-amine (CP-96,345, 10 mg/kg/day, i.p.), CP-99,994 (10 mg/kg/day, i.p.), nor a 14-day of treatment with (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994, 10 mg/kg/day, s.c.) significantly modified the firing rate of noradrenaline neurons.  

In the brainstem we observed activity in the dorsal rostral pons (representing the Kölliker-Fuse/parabrachial (KF/PB) nuclei and Locus coeruleus), the inferior ventral pons and the dorsal and lateral medulla.  

We have previously shown that the descending pathways from the Locus coeruleus (LC)/subcoeruleus (SC) to the spinal cord are activated during peripheral inflammation, and that activation of this coeruleospinal system decreases development of hyperalgesia.  

For all drugs tested, reductions of NET and SERT protein were not accompanied by reduced NET or SERT mRNA in Locus coeruleus or dorsal raphe nucleus, respectively.  

Five general brain regions contained retrogradely labeled neurons: cerebral cortex (infralimbic and insular regions), rostral forebrain structures (subfornical organ, organum vasculosum of the lamina terminalis, taenia tecta, nucleus accumbens, lateral septum, endopiriform nucleus, dorsal BST, substantia innominata, and, most prominently the amygdala-primarily its basomedial and central subnuclei), thalamus (central medial, intermediodorsal, reuniens, and, most prominently the paraventricular thalamic nucleus), hypothalamus (medial preoptic area, perifornical, arcuate, dorsomedial, parasubthalamic, and posterior hypothalamic nuclei), and brainstem (periaqueductal gray matter, dorsal and central superior raphe nuclei, parabrachial nucleus, pre-Locus coeruleus region, NTS, and A1 noradrenergic neurons in the caudal ventrolateral medulla).  

Comput Biomed Res 1996;29:162-73] brain-mapping software to successfully localize several regions of macaque cortex, including the middle temporal area, the lateral intraparietal area and the frontal eye field, and one subcortical structure, the Locus coeruleus, for electrophysiological recordings..  

We found that stereotaxic injection of TH promoter containing adenoviral construct resulted in cell-type-specific transgene expression in the noradrenaline (NA) neurons of the Locus coeruleus (LC).  

The tangential migration from the dorsal rhombomere (r) 1 to the dorsolateral pontine tegmentum is a crucial event in the development of Locus coeruleus (LC), but the molecular mechanisms underlying the migration are not well understood.  

Additionally, outside of the hypothalamus, labeling was observed in the thalamic parafascicular nucleus, the Edinger-Westphal nucleus, Locus coeruleus, ventral raphe system, nucleus of solitary tract and in the preganglionic sympathetic intermediolateral cell column of the spinal cord, and the pituitary anterior and intermediate lobes.  

Low and high E(2) treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and Locus coeruleus.  

Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, Locus coeruleus, ventral subcoeruleus nucleus, and raphe nuclei.  

Noradrenergic projections from the Locus coeruleus (LC) project to the olfactory bulb (OB), a cortical structure implicated in odor learning and perceptual differentiation among similar odorants.  

However, no corresponding changes were found in the expression of tyrosine hydroxylase (TH) mRNA in the noradrenergic neurons of the Locus coeruleus (LC).  

During odour stimulation, migraineurs also showed significantly higher activation than controls in the left temporal pole and significantly lower activation in the frontal (left inferior as well as left and right middle frontal gyri) and temporo-parietal (left and right angular, and right posterior superior temporal gyri) regions, posterior cingulate gyrus and right Locus coeruleus.  

Locus coeruleus neuron extracellular single-unit spontaneous discharge was recorded in anesthetized animals after Sazetidine-A and epibatidine. Epibatidine excited Locus coeruleus neurons, whereas Sazetidine-A had no effect on these neurons.  

Besides, they were differentially expressed in the medial vestibular nucleus, Locus coeruleus and the ventral medulla.  

The present study was conducted to examine the effects of prolonged bupropion administration on the firing activity of dorsal raphe nucleus (DRN), Locus coeruleus (LC), and ventral tegmental area (VTA) neurons.  

While the acute inhibitory effect of opioids on Locus coeruleus (LC) neurons is mediated primarily by the activation of G protein-gated inwardly-rectifying K(+) (GIRK) channels, the 3'-5'-cyclic adenosine monophosphate (cAMP) system has been implicated in the effects of chronic morphine exposure.  

Finally SR58611A increased the firing rate of noradrenergic neurons in the rat Locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 muM) but not chronic (10 mg/kg, p.o.) administration.  

Compared with the control group, blood volume-expanded rats showed a significant greater number of Fos-FG double-labeled cells along the nucleus of the solitary tract, Locus coeruleus, hypothalamic paraventricular nucleus, central extended amygdala complex, and dorsal raphé nucleus (DRN) cells.  

Previous studies in rats have reported that the Locus coeruleus (LC), a catecholaminergic nucleus in the brain stem, is sexually dimorphic such that females have more neurones than males.  

Moderate levels were observed in some amygdaloid nuclei, CA2 area and dentate gyrus of hippocampus, endopiriform nuclei, globus pallidus, striatum, molecular layer of cerebellum, and Locus coeruleus, whereas no expression was detected in hypothalamic nuclei, CA1 and CA3 areas of hippocampus, zona incerta.  

Moreover, the Locus coeruleus (LC) projects from the pons through the rat sensorimotor cortex, and injury axotomizes LC fibers, depressing NA function.  

LR animals did not however yield any significant difference in mu opioid receptor mRNA levels in Locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals.  

Social interaction-induced neuronal activation patterns were studied in the prefrontal cortex (orbitofrontal and medial), amygdala (central, medial, and basolateral), dorsal raphe and Locus coeruleus.  

In Locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury, gabapentin reduced the gamma-aminobutyric acid (GABA) type A receptor-mediated inhibitory postsynaptic currents (IPSCs).  

Serotonergic neurons in the raphe nuclei also receive noradrenergic innervation arising from the Locus coeruleus and alpha-1 and alpha-2 adrenoceptors inhibited [ (3)H]5-HT release in our experimental conditions.  

The basolateral amygdala (BLA) receives dense norepinephrine (NE) innervation from the Locus coeruleus, and stressful and conditioned stimuli cause increases in NE levels within the BLA.  

In the pons, Barrington's nucleus and the norepinephrine (NE) nucleus, Locus coeruleus (LC), are integral to a circuit that links the pelvic viscera with the forebrain and coordinates pelvic visceral activity with arousal and behavior.  

In the present study, the effects of intra-Locus coeruleus (LC) injection of GABA(B) receptor-interacting agents on naloxone-induced withdrawal signs of morphine-dependent rats were examined.  

BP(ND) values by the indirect kinetic method were 0.54 +/- 0.19 and 0.35 +/- 0.25 in the thalamus and Locus coeruleus, respectively.  

Patients with mild cognitive impairment (MCI), who are at risk for Alzheimer's disease (AD), or those with early AD, exhibit noradrenergic degeneration in the Locus coeruleus. These observations suggest that noradrenergic damage in the Locus coeruleus may facilitate cholinergic and serotonergic functions in the hippocampus.  

This study demonstrates that administering rats either cocaine or a selective serotonin (or 5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) for 16 weeks results in reduced density of dopaminergic and noradrenergic terminals in the striatum and olfactory bulb, respectively, reflecting pruning of the terminal arbor of ventral midbrain dopaminergic and Locus coeruleus noradrenergic neurones.  

Here, we present theoretical work suggesting that the noradrenergic nucleus Locus coeruleus (LC) may help optimize 2AFC decision making in the brain.  

In the brainstem, high binding was detected around the cerebral aqueduct of the midbrain and within the dorsal pons, in a volume comprising Locus coeruleus.  

The recruitment of "alternative" pathways, such as PAG-Locus coeruleus (LC)-spinal cord might be responsible for AA-5-HT effect since we found evidence that (i) intra-PAG AA-5-HT increased LC neuron firing activities, and (ii) intrathecal phentolamine or ketanserin prevented the analgesic effect of AA-5-HT.  

Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA.To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter.Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas.Systemic administration or intra-cortical perfusion of alpha(2)-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex.Chemical modulation of the Locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC.Electrical stimulation of the Locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced.Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of alpha(2)-adrenoceptors.  

Activation of noradrenergic Locus coeruleus (LC) neurons promotes wakefulness and behavioral arousal.  

Interaction of the pedenculo-pontine and lateral dorsal tegmental areas with the dorsal raphae nucleus and Locus coeruleus, is important for REM sleep generation.  

In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the Locus coeruleus. In the Locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level.  

The projections from prefrontal cortex to spinal motoneurones and the balance between the activation of the right and left cortical hemisphere are considered responsible for the hypnotizability-related modulation of reflex responses, while the differences in postural control between subjects with high (highs) and low (lows) hypnotic susceptibility are considered a possible consequence of the activity of the Locus coeruleus, which is also involved in attention, and of the cerebellum, which might be responsible for different internal models of postural control.  

RESULTS: A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left Locus coeruleus, the thalamus (left >> right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula.  

The purpose of the present investigation was to examine whether electrical stimulation in the Locus coeruleus/subcoeruleus (LC/SC) could modulate visceral pain evoked by noxious colorectal distention (CRD).  

Despite considerable evidence suggesting the relationship between the central noradrenergic (NA) system and fear/anxiety states, previous animal studies have not demonstrated sheer involvement of the Locus coeruleus (LC) in mediating fear or anxiety.  

Other neuromodulatory systems, such as noradrenergic Locus coeruleus neurons, give rise to highly diffuse projections through brain and spinal cord and simultaneously stimulate cortical activation and behavioral arousal.  

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by highly selective neuronal cell death in the substantia nigra and the Locus coeruleus with no Lewy body formation.  

We first tested the hypothesis that the pons (which includes noradrenergic neurons from the Locus coeruleus; LC) plays a role in the lung burst frequency response to central hypoxia by comparing the effects of brainstem transection at the LC level between pre-metamorphic tadpoles and adults.  

In rats exposed to footshocks, we then investigated the activity of corticotrophin-releasing factor (CRF) as well as indexes of catecholamine ir, namely tyrosine hydroxylase (TH) immunopositive neurons in the paraventricular nucleus (PVN), TH immunopositive neurons in the Locus coeruleus, and phenylethanolamine N-methyltransferase (PNMT) immunopositive neurons in the brain stem.  

In the brainstem, Oxt-ir fibers were found in the periaqueductal gray, Locus coeruleus, parabrachial nucleus, nucleus of the solitary tract, and nucleus ambiguus.  

Many brain nuclei composing a complicated network are involved in processing acupuncture analgesia, including the nucleus raphe magnus (NRM), periaqueductal grey (PAG), Locus coeruleus, arcuate nucleus (Arc), preoptic area, nucleus submedius, habenular nucleus, accumbens nucleus, caudate nucleus, septal area, amygdale, etc.  

The Locus coeruleus (LC) is the main source of noradrenergic innervations to the forebrain and the hippocampal formation but does not receive noradrenergic projections itself.  

Researchers are beginning to identify brain sites associated with conditioned contextual fear such as the ventral anterior olfactory nucleus, dorsal premammillary nucleus, ventrolateral periaqueductal gray, cuneiform nucleus, and Locus coeruleus.  

Our postmortem study aimed to determine the impact of suicide on the number of noradrenergic neurons of the Locus coeruleus (LC) in suicidal depressive patients.  

NPR-C immunoreactivity was detected in several regions, including the periaqueductal gray, oculomotor nucleus, red nucleus and trochlear nucleus of the midbrain; the pontine nucleus, dorsal tegmental nucleus, vestibular nucleus, Locus coeruleus, trigeminal motor nucleus, nucleus of the trapezoid body, abducens nucleus and facial nucleus of the pons; and the dorsal motor nucleus of the vagus, hypoglossal nucleus, lateral reticular nucleus, nucleus ambiguus and inferior olivary nucleus of the medulla oblongata.  

The results indicate a higher prevalence of pathological features in depressed compared to non-depressed PD patients, particularly in catecholamine areas of the brain; the Locus coeruleus (neuronal loss: odds ratio=7.2, p=08; gliosis: odds ratio=18.0, p=008); dorsal vagus nerve (gliosis: odds ratio=7.63, p<0.05), and substantia nigra pars compacta (gliosis: odds ratio=2.85, ns).  

Effects of Locus coeruleus (LC) stimulation on the impulse activity of bulbar respiration neurons in rats were studied on a background of varying hypoxia.  

By contrast, acute Fos induction was enhanced in noradrenergic neurons in the Locus coeruleus following CIH exposure.  

Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the Locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD.  

After Gdnf ablation, mice showed a progressive hypokinesia and a selective decrease of brain tyrosine hydroxylase (Th) mRNA, accompanied by pronounced catecholaminergic cell death, affecting most notably the Locus coeruleus, which practically disappears; the substantia nigra; and the ventral tegmental area.  

The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in Locus coeruleus.  

Counts of the number of Locus coeruleus neurons corresponded with the number of neurons found in the brains of healthy people of 60-80 years old.  

The present study was performed to test two hypotheses: (1) that potentials in the domain of seconds (0.1-0.5 Hz) reflect specific and direct interactions of the MGN and A1 during neural processing of sensory information, and (2) that low-frequency infraslow potentials in the A1 (<0.1 Hz) are related to brainstem influences originating from the Locus coeruleus (LC) and dorsal raphe nucleus (DRN).  

Parkinson's disease (PD) is characterized not only by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) but also by a degeneration of Locus coeruleus (LC) noradrenergic neurons.  

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the Locus coeruleus (LC).  

Nowadays, the great majority of studies highlight the need for silence in the Locus coeruleus noradrenergic neurons as a condition for the occurrence and maintenance of REM sleep.  

In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), Locus coeruleus, hippocampus and cortex.  

Ngb-ir neurones co-localise heme oxygenase 1 (HO-1) in the LDTg and Locus coeruleus.  

This is consistent with studies showing that galanin decreases activity-evoked dopamine release in striatal slices and decreases the firing rate of noradrenergic neurons in Locus coeruleus, areas involved in drug reward and withdrawal, respectively.  

Noradrenergic input from the Locus coeruleus controls memory processing at two critical times after training-acquisition (0-2.5 min after training) and consolidation (25-30 min after training).  

Withdrawal from morphine leads to the appearance of extreme anxiety accompanied of several physical disturbances, most of them linked to the activation of brainstem regions such as the Locus coeruleus, ventral tegmental area, hypothalamic nuclei and periaqueductal grey (PAG).  

The Locus coeruleus of the laboratory rat differs in location to that observed for the Cape porcupine and several other rodent species.  

This study examined the effects of intra-Locus coeruleus injection of a gamma-amino-butyric acid type A (GABAA) receptor agonist on naloxone-induced withdrawal signs of morphine-dependent rats.  

We investigated whether inter-individual variability in novelty-induced behaviors in C57BL/6J mice correlates with numbers of noradrenergic neurons in the Locus coeruleus and cholinergic neurons in the septum.  

These different patterns of recruitment may reflect inputs to the ventral attention network from the Locus coeruleus/norepinephrine system.  

Chronic stress exposure alters the central noradrenergic neurons originating from the Locus coeruleus (LC).  

Within the mid- and hindbrain Ngb expressing neurones were found in the laterodorsal tegmental nucleus, the pedunculo pontine tegmental nucleus, the Locus coeruleus, and the lateral parabrachial nucleus.  

Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotional-arousal (amygdala, rostral and subgenual cingulate regions, and Locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices).  

Fourteen days post-ADX, as expected, plasma ACTH was elevated, and levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and MC2R mRNAs in superior cervical ganglia (SCG), and TH mRNA in Locus coeruleus (LC) were increased compared with sham-operated animals.  

Two weeks after footshock treatment NPY mRNA expression was increased in the basolateral amygdala and showed preshockxnoise interaction in the Locus coeruleus (down after noise in controls, lower basal and unchanged after noise in preshocked). Altered expression of NPY in the basolateral amygdala and Locus coeruleus could contribute to or compensate for behavioural and autonomic sensitisation in preshocked rats.  

alpha(1)-Adrenoceptors of the Locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established.  

Strikingly, we also found that NA neuron development was significantly compromised in the Locus coeruleus as well.  

We analyzed the electrophysiological patterns of synchronization of cortical EEG (areas 4, 5, 7, 21, 17, 18, 22) and thalamic field (EThG) (ventral posterior lateral nucleus-VPL), and the influence of modulatory systems originating in the pedunculo-pontine tegmentum (PPT) and Locus coeruleus (LC) on the discharge pattern of thalamic neurons during OA.  

evoked a significant expression of Fos, an immediate-early transcription factor in neurons, on the dopamine-beta-hydroxylase-containing neurons and alpha(3) nicotinic acetylcholine receptor subunit-expressing neurons in the Locus coeruleus, but not in the medullary A(1) and A(2) regions containing noradrenergic neurons. These results suggest that centrally administered corticotrophin-releasing factor elevates plasma corticosterone by the corticotropin-releasing factor 1 receptor and alpha(3) subunit-containing nicotinic acetylcholine receptor (probably alpha(3)beta(2) nicotinic acetylcholine receptor) mediated activation of the Locus coeruleus noradrenergic neurons projecting to the paraventricular nucleus in rats..  

Using immunohistochemistry, c-Fos, a marker of cell activation, was quantified in the nucleus accumbens (Acb), lateral hypothalamus (LH), ventral tegmental area (VTA), and Locus coeruleus (LC).  

Recovery of consciousness was associated with normalizing rCMRglc in visual, auditory, and somatosensory cortices and in the Locus coeruleus (47 regions affected, 31% decrease).  

We examined 5-HT input and NE neurons in the Locus coeruleus (LC, the NE nucleus that innervates the forebrain) in BD by quantifying immunoreactivity (IR) for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the biosynthetic enzymes for NE and 5-HT, respectively.  

To investigate the involvement of the noradrenergic Locus coeruleus (LC) in the reflex blink circuit, c-Fos and neuronal tracer experiments were performed in the rat.  

Lower but distinct GR-ir was observed in the internal granule cell layer of the olfactory bulbs, dorsal and lateral pallium, striatum, various subfields of the amygdala, bed nucleus of the stria terminalis (BNST), optic tectum, various tegmental nuclei, Locus coeruleus, raphe nuclei, reticular nuclei, and the nuclei of the trigeminal motor nerves.  

The noradrenergic nucleus Locus coeruleus (LC) densely innervates limbic structures.  

Because the fetus is mostly asleep, and hunger is a physiological state unlikely to arise until birth, we hypothesized that orexigenic neurons in the lateral and dorso-medial hypothalamic areas (LHA, DMH) and their projections to the Locus coeruleus (LC) would develop only near the time of birth.  

While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, Locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula.  

We further confirmed the existence of noradrenergic afferents onto CRNs from the Locus coeruleus by combining tyrosine hydroxylase immunohistochemistry and tract-tracing experiments.  

One site at which opiates and stress substrates may interact to have global effects on behavior is within the Locus coeruleus (LC).  

The Locus coeruleus (LC) provides the sole source of norepinephrine (NE) to the cortex for modulation of cortical synaptic activity in response to salient sensory information.  

Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the Locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal.  

The mammalian main olfactory bulb receives a significant noradrenergic input from the Locus coeruleus.  

We also investigated the effect of morphine and beta-endorphin on pERK and pCaMK-IIalpha expression in the Locus coeruleus (LC). injection of morphine significantly increased pERK as well as pCaMK-IIalpha expression in the Locus coeruleus, while beta-endorphin increased only pCaMK-IIalpha in the LC.  

Using an immature animal model, the postnatal day (P)-3 (P3) rat pup, we investigated the effects of HI on brainstem catecholamine neurons in the Locus coeruleus, nucleus tractus solitarius (NTS), and ventrolateral medulla (VLM). On P21, we found that prior P3 HI significantly reduced numbers of catecholaminergic neurons in the Locus coeruleus, NTS, and VLM. Only Locus coeruleus A6, NTS A2, and VLM A1 noradrenergic neurons, but not NTS C2 and VLM C1 adrenergic neurons, were lost.  

In neurons of the periphery and Locus coeruleus, this up-regulation is associated with an initial induction of TH mRNA.  

We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep-waking rhythms and impairment of the noradrenergic (NA)-Locus coeruleus (LC) system.  

We recorded neuronal activity in the rat noradrenergic nucleus Locus coeruleus (LC) using chronically implanted movable microelectrodes while monitoring the behavioral state via electrocorticogram and online video recording.  

The midline and intralaminar thalamic nuclei (MITN), Locus coeruleus (LC) and cingulate cortex contain nociceptive neurons.  

Because the noradrenergic nucleus Locus coeruleus (LC) is activated by cold stress and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway, this study aimed to evaluate the LC's role in cold stress-induced PCO in rats.  

Amygdala, posterior cingulate, Locus coeruleus, and substantia nigra showed selective sensitivity to food-related cues when hungry but not when satiated, an effect that did not generalize to tools.  

It is well known that noradrenergic Locus coeruleus neurons decrease their activity during slow wave sleep and are quiescent during paradoxical sleep. By using anterograde tract-tracing, we further showed that the DPGi, in addition to Locus coeruleus, directly projected to other areas containing wake-promoting neurons such as the serotonergic neurons of the dorsal raphe nucleus and hypocretinergic neurons of the posterior hypothalamus.  

We evaluated the electrophysiologic response of Locus coeruleus neurons to the systemic and local infusion of epibatidine. Rats were anesthetized with 2% halothane and single-unit Locus coeruleus discharge was recorded after administration of systemic (2.5, 5 and 10 microg/kg subcutaneously) and intracoerulear (0.03-0.01-0.001 microg) epibatidine. The subcutaneous epibatidine activated Locus coeruleus neurons only at the highest dose (10 microg/kg). The 2.5-5 microg/kg doses, previously shown to induce analgesia, did not activate Locus coeruleus neurons. The intracoerulear infusion of epibatidine induced excitement of Locus coeruleus neurons at every tested dose. The intra-dorsal raphe infusion of 0.03 microg epibatidine induced significant excitation of Locus coeruleus neurons. These data show that the administration of epibatidine induces excitation of Locus coeruleus neurons, which is mediated by nicotinic receptors. The response of Locus coeruleus neurons to systemic and locally administered epibatidine is dose-related..  

Medium-sized neurons were labeled in telencephalic, diencephalic, and mesencephlic areas, whereas densely labeled large neurons were found in rhombencephalon, Locus coeruleus, reticular formation, oculomotor area, medial octavolateralis and magnocellular octaval nuclei, and Purkinje cell somata.  

In both vehicle-treated and euhydrated rats, AM2-LI neurons were observed in the hypothalamus and brainstem, including in the organum vasculosum of the lamina terminalis, the median preoptic nucleus, the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the ventromedial hypothalamic nucleus, the arcuate nucleus, the Locus coeruleus, the nucleus of the tractus solitarius and the nucleus ambiguus.  

The Locus coeruleus (LC) located at the level of the pons, is involved in cognitive functions such as learning and memory. In conclusion, it seems that the nucleus Locus coeruleus does not affect acquisition while it involves in the memory consolidation and retrieval of inhibitory avoidance learning task..  

BACKGROUND: Through their action on the Locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions.  

Interestingly, rotenone also caused significant noradrenergic neuronal loss in the Locus coeruleus.  

The NGF administration in stressed mice reverted the stress-induced up-regulation of TH levels in male and female mice hypothalamic nuclei and in male Locus coeruleus.  

CRF (100 ng) administered into the Locus coeruleus (LC) almost tripled microdialysate concentrations of NE in the PFM.  

In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the Locus coeruleus.  

Results showed that TASK-1 mRNAs were widely distributed on the putative central chemoreceptors such as Locus coeruleus, nucleus tractus solitarius and medullary raphe, etc.  

The amygdalae send impulses to the hypothalamus for activation of the sympathetic nervous system, to the reticular nucleus for increasing reflexes, to the nuclei of the trigeminal nerve and facial nerve for facial expressions of fear, and to the ventral tegmental area, Locus coeruleus, and laterodorsal tegmental nucleus for activation of dopamine, norepinephrine and epinephrine release.  

The time frame of the regulation of gene expression, especially as it relates to catecholamine (CA) biosynthetic enzymes are compared in three crucial catecholaminergic locations, the adrenal medulla, sympathetic ganglia and Locus coeruleus in male animals. The Locus coeruleus, origin of most of the noradrenergic neurons innervating much of the brain, displays activation of additional signalling pathways and transcription factor with repeated compared to single exposure to stress. Key words: Adrenal medulla - Catecholamine biosynthesis - Estrogen - Sympathetic ganglia - Locus coeruleus - Stress - Transcription factors..  

Although hypothalamic-pituitary-adrenal axis activation is generally considered to be the hallmark of the stress response, many of the same stimuli that initiate this response also activate the Locus coeruleus-norepinephrine system. Given its functional attributes, the parallel engagement of the Locus coeruleus-norepinephrine system with the hypothalamic-pituitary-adrenal axis serves to coordinate endocrine and cognitive limbs of the stress response. The elucidation of stress-related afferents to the Locus coeruleus and the electrophysiological characterization of these inputs are revealing how the activity of this system is fine-tuned by stressors to facilitate adaptive cognitive responses. The net effect of these interactions is to adjust the activity and reactivity of the Locus coeruleus-norepinephrine system such that state of arousal and processing of sensory stimuli are modified to facilitate adaptive behavioral responses to stressors. This review begins with an introduction to the basic anatomical and physiological characteristics of Locus coeruleus neurons. The concept that Locus coeruleus neurons operate through two activity modes, i.e., tonic vs. Anatomical and physiological evidence are then presented suggesting that interactions between stress-related neurotransmitters that converge on Locus coeruleus neurons regulate shifts between these modes of discharge in response to the challenge of a stressor. This review focuses specifically on the Locus coeruleus because it is the major source of norepinephrine to the forebrain and has been implicated in behavioral and cognitive aspects of stress responses..  

Because pupil dilation reflects levels of norepinephrine (NE) released from the Locus coeruleus (LC), we interpret these results as suggestive that the LC-NE complex may play the same role in perceptual selection as in behavioral decision making..  

The substantia nigra, midbrain raphe and Locus coeruleus showed normal or increased (18)F-dopa uptake until PD was advanced, indicating compensatory responses in intact monoamine neuron perikarya.  

Noradrenergic neurons of the Locus coeruleus (LC) have provided a useful model system in which to understand the molecular basis of these adaptive changes.  

These data are congruent with the hypothesis that carbachol-inhibited GABAergic PnO neurons project to, and inhibit, REM-on SubC reticular neurons during waking, whereas carbachol-excited SubC and PnO GABAergic neurons are involved in silencing Locus coeruleus and dorsal raphe aminergic neurons during REM sleep.  

With regard to the reciprocal interaction between DA and NE neurons, it was observed that the selective loss of DA neurons achieved by the intra-ventral tegmental area (VTA) injection of 6-OHDA increased the firing activity of a subset of Locus coeruleus (LC) NE neurons by 47%.  

Through a highly divergent efferent projection system, the Locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. State-dependent neuronal discharge activity of Locus coeruleus neurons has long-suggested a role of this system in the induction of an alert waking state. More recent work supports this hypothesis, demonstrating robust wake-promoting actions of the Locus coeruleus-noradrenergic system. Recent anatomical studies suggest that arousal-enhancing actions of norepinephrine are not limited to the Locus coeruleus system and likely include the A1 and A2 noradrenergic cell groups.  

The nuclei within the song control circuit receive projections from catecholaminergic cell populations involved in attention, arousal and motivation, including periaqueductal gray (PAG), ventral tegmental area (VTA), Locus coeruleus (LoC) and sub coeruleus (SC).  

We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), Locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats.  

To clarify the supraspinal mechanism of action of gabapentin, whole-cell patch-clamp recordings were performed on Locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury or mice subjected to a sham-operation, and the effects of gabapentin in the modulation of synaptic transmission were studied.  

The present study on rat examined the role of galanin receptor subtypes in regulation of depression-like behavior as well as potential molecular mechanisms involved in the Locus coeruleus (LC) and dorsal raphe (DR).  

We found that these PT neurons and two other GFP labeled non-TH type neuronal groups, one in the paraventricular organ of the posterior tuberculum and the other in the hypothalamus, were significantly reduced after exposure to MPTP, while the rest of GFP-positive neuronal clusters, including those in telencephalon, pretectum, raphe nuclei and Locus coeruleus, remain largely unchanged.  

In the paraventricular nucleus of the hypothalamus (PAH), lateral hypothalamic area (LH), paraventricular nucleus of the thalamus (PVT), periaqueductal gray matter (PAG), bed nucleus of the stria terminalis (BNST), Locus coeruleus (LC), lateral parabrachial nucleus (Pbl), the complex of the solitary tract nucleus (NTS) and dorsal motor nucleus of the vagus nerve (DMX), numbers of neurons expressing c-Fos protein were much higher in test than in control experiments.  

When administered systemically, the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) appears to target the noradrenergic innervation originating in the Locus coeruleus causing long-term decrements in noradrenergic function. Within 20 days, DSP-4 treatment profoundly reduced the number of DBH-ir cells in both the Locus coeruleus and ventral subcoeruleus.  

Then, we presented a primary description of ion channels, including voltage-gated Na(+), K(+) and Ca(2+) channels in Locus coeruleus (LC) neurons in rat brain slices.  

Pontine noradrenergic neurons of the Locus coeruleus (LC) and sub-coeruleus (SubC) region cease firing during rapid eye movement sleep (REMS).  

Selected post-mitotic populations, such as the Locus coeruleus, appear to both make and break down retinoic acid suggesting that a requirement for an autocrine, or at least a highly localised paracrine signalling network, might explain its acute sensitivity to retinoic acid disruption.  

The present study examined the influence of pharmacological modulations of the Locus coeruleus noradrenergic system on odor recognition in the mouse.  

Our recent data, obtained using a zymosan-induced inflammatory air pouch model in mice, have demonstrated that subcutaneous bee venom (BV) injection into the hind limb selectively activates the contralateral brain stem Locus coeruleus (LC) and then via a descending noradrenergic pathway and subsequent adrenal medullary catecholamine release induces a potent anti-inflammatory effect.  

In the present study, the pharmacologic properties of Wf-516 were thus assessed using in vivo electrophysiology in the rat dorsal raphe nucleus (DRN), Locus coeruleus (LC) and hippocampus.  

The local administration of clonidine into the bilateral Locus coeruleus (LC) evoked burst discharges during the expiratory phase in the IX motor rootlet.  

Zebrafish lmx1b.1 is expressed in noradrenergic neurons of the Locus coeruleus and medulla oblongata, but knock-down reveals that it is specifically required for tyrosine hydroxylase expression only in the medulla oblongata area postrema noradrenergic neurons.  

Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, Locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1.  

The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in Locus coeruleus.  

During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the Locus coeruleus.  

The Locus coeruleus (LC) is a source nucleus of widely spreading noradrenergic projections in the central nervous system and is also known as one of the principal targets of some alpha2-adrenoceptor agonists, such as dexmedetomidine.  

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the Locus coeruleus, the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH).  

The following brain regions were examined: cingulate cortex, cerebellum, nucleus accumbens, caudate nucleus, putamen, pons, hippocampus, Locus coeruleus, and basal ganglia.  

Further, EA activated serotonin- and catecholamine-containing neurons in the nucleus raphe magnus and Locus coeruleus that project to the spinal cord.  

In addition, P2X(4) immunostaining demonstrated the existence of neuronal degeneration in the Locus coeruleus, reticular formation, and Purkinje cells of the cerebellar cortex.  

Catecholaminergic neurons of the primate substantia nigra (SN) pars compacta (SNc) and the Locus coeruleus contain neuromelanin (NM) granules as characteristic structures underlying the pigmentation of these brain areas. Since tyrosinase mRNA is suggested to be expressed in the SN of mice and humans, we reinvestigated the expression of tyrosinase in the human SNc and the Locus coeruleus at the protein level by immunohistochemistry and Western blot analysis, but could not detect tyrosinase in these brain regions..  

Dense localization of NPY and NPY receptors is found in brain areas implicated in psychopathology such as the amygdala, hippocampus, neocortex, septum, caudate-putamen, hypothalamus and Locus coeruleus.  

In an effort to learn more about the cell type-specific functional role of parkin, we used in vitro model such as Locus coeruleus (LC) noradrenergic (NA) neuronal progenitor cell line, LC3541.  

Of the labelled cell bodies in the subcortical structures, about 38.8% were located in the ipsilateral basal forebrain (10.6% in the lateral amygdala LA, 11.5% in the globus pallidus GP, 3.7% in the ventral pallidum VPa, 13.0% in the nucleus basalis NB), 13.1% in the ipsi- and contralateral diencephalon (6.4% in the posterior paraventricular thalamic nuclei, 6.7% in the hypothalamic area), and 48.1% in the midbrain (20.0% in the ipsilateral substantia nigra, 9.8% in the ipsi- and contralateral ventral tegmental area, 5.0% in the ipsi- and contralateral Locus coeruleus, 13.3% the ipsi- and contralateral dorsal raphe nuclei).  

Electrical stimulation of the pinna induced significant increases in the number of Fos-positive neurons in the DCN, spinal trigeminal nucleus (Sp5), dorsal raphe nucleus (DR) and Locus coeruleus (LC).  

Recent evidence has suggested that kappa opioid receptor agonists decrease dopaminergic and noradrenergic neurotransmission in prefrontal cortex and Locus coeruleus.  

Among the various nervous systems and signaling components involved in the development of morphine withdrawal symptoms, sensitization of the brain dopaminergic nervous system and an increase in the cAMP levels in the Locus coeruleus are believed to be the most important cellular events. In addition, EGCG showed moderate inhibitory effects on the morphine-induced increase in the cAMP levels in the Locus coeruleus at 100 mg/kg and the signaling of the dopamine D2 receptor at 100 microM. These results suggest that EGCG has strong pharmacological activity against the development of morphine dependence, which can be partly explained by its inhibitory effects on the morphine-induced increase in the cAMP levels in the Locus coeruleus and the signaling of the dopamine D2 receptor..  

Acute VNS significantly increased c-Fos staining in the nucleus of the solitary tract, paraventricular nucleus of the hypothalamus, parabrachial nucleus, ventral bed nucleus of the stria terminalis, and Locus coeruleus but not in the cingulate cortex or dorsal raphe nucleus (DRN).  

There are also specific visual and auditory thalamic inputs, while specific motivating catecholaminergic mesencephalic afferents include the ventral tegmental area, the substantia nigra and the Locus coeruleus.  

Corticotropin-releasing factor (CRF) activates Locus coeruleus (LC)-norepinephrine neurons during stress.  

Projections from the MnPO to the Locus coeruleus were observed within and surrounding the tyrosine hydroxylase-IR cell cluster.  

The present study was designed to examine whether visceral nociceptive transmission in the two different areas is under the control of the centrifugal pathways from the Locus coeruleus/subcoeruleus (LC/SC).  

In addition, we measured the level of noradrenaline and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the Locus coeruleus, hypothalamus, hippocampus and cerebellum in stressed mice. Moreover, chronic tramadol and desipramine treatment increased the level of noradrenaline (NA) and MHPG in the Locus coeruleus but not in the cerebellum, whereas only MHPG level was increased in the hypothalamus.  

CONCLUSIONS: These effects of modafinil are best explained via an activation of the hypoxia-sensitive nucleus Locus coeruleus.  

Aberrant oxidation of norepinephrine (1) via the transient o-quinone has been implicated as a critical pathogenetic mechanism underlying the degeneration of noradrenergic cell bodies in the Locus coeruleus in Parkinson's disease, the degeneration of noradrenergic nerve terminals in Alzheimer's disease and following transient cerebral ischemia, and the onset and progression of idiopathic vitiligo. An oxidative pathway of 1 is also believed to account for the slow deposition of neuromelanin in pigmented neurons of the Locus coeruleus. Overall, the results of this study provide a complete characterization of the oxidative chain fission pathways of 1, highlight 3,4-dihydroxyphenylglyoxylic acid as a novel possible metabolic product of this catecholamine, and yield an insight into norepinephrine-melanin, a putative component of Locus coeruleus neuromelanin..  

Locus coeruleus degeneration might influence the response to dopamine replacement and the presence of long-term complications such as dyskinesias. Each study was done in two experimental conditions: a) rats with unilateral 6-OHDA lesion and b) rats with a lesion of the nigrostriatal pathway (6-OHDA) combined with selective denervation of Locus coeruleus-noradrenergic terminal fields by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4).  

It is noted that the Locus coeruleus of the laboratory rat differs in appearance to that reported for several other rodent species.  

Autosomal recessive mutations within the Parkin gene are associated with degeneration of the substantia nigra and Locus coeruleus and an inherited form of Parkinson's disease (PD).  

The striatal enriched RGS9 plays a prominent role in opiate and psychostimulant drug reward; RGS4 appears to modulate opiate dependence via actions in the Locus coeruleus, whereas RGSz modulates analgesia via activation of the PKC pathway..  

The effect of paraquat on catecholaminergic neurons was reminiscent of that of Parkinson's disease, with preferential loss of dopaminergic neurons in the ventral tier of the substantia nigra pars compacta and loss of tyrosine hydroxylase staining in the Locus coeruleus.  

Thus, by using a dual-probe microdialysis approach in freely moving animals, the aim of the present study was to investigate whether a relevant stressor can trigger the release of SP in the Locus coeruleus (LC) and whether and how this response modulates noradrenaline (NA) transmission both in the LC and in the medial prefrontal cortex (mPFC), an important LC terminal region involved in emotional processing.  

Neuropathology shows severe neuronal loss in the substantia nigra, less prominent neuronal loss in the Locus coeruleus, and no or few Lewy bodies.  

A form of enriched rehabilitation was used to rehabilitate animals after ischemia and the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine was used to selectively destroy norepinephrine projections from the Locus coeruleus.  

In contrast, patients with atypical features are characterized by reduced activity of the HPA axis and ascending noradrenergic neurons in the Locus coeruleus.  

The Locus coeruleus (LC) has been suggested as a CO(2) chemoreceptor site in mammals.  

Fos-immunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and Locus coeruleus) was strongly reduced after chronic administration.  


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