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Results for “Locus Coeruleus”

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PubMed1997

Antidromic burst activity of locus coeruleus neurons during cortical spreading depression.

The electrical activity of locus coeruleus neurons was investigated during cortical spreading depression in urethane-anaesthetized rats. Cortical spreading depression was induced by a direct application of 1-3 M KCl solution to the surface of the cerebral cortex. The occurrence of cortical spreading depression was assessed by recording negative d.c. shifts and in some experiments by monitoring the extracellular potassium concentrations. The mean spontaneous firing rate of locus coeruleus neurons was significantly reduced during cortical spreading depression. Approximately 60% of locus coeruleus neurons recorded during cortical spreading depression revealed anomalous burst activity consisting of multiple initial segment spikes as well as full initial segment-somatodendritic spikes with a marked initial segment-somatodendritic break. Each spike of the cortical spreading depression-related burst activity occurred at intervals ranging from 15.0 ms to 90.1 ms (34.9 +/- 0.5 ms). The burst activity appeared unpredictably at variable intervals in a phasic or tonic manner during cortical spreading depression. The cortical spreading depression-related burst activity of locus coeruleus neurons mimicked antidromic spikes induced by train stimulation of the cerebral cortex at short interspike intervals during iontophoretic application of GABA to locus coeruleus neurons, whereas it was totally different from synaptically-activated burst activity induced by tail pinch. The full spikes and initial segment spikes in the cortical spreading depression-related burst activity failed to collide with cortically elicited antidromic spikes, even when they appeared within the collision interval. The proportion of initial segment spikes in the cortical spreading depression-related burst activity was reduced following an increase in membrane excitability by iontophoretic application of glutamate, and increased during a decreased membrane excitability by GABA application. The antidromic burst activity of locus coeruleus neurons also appeared for a short time during cortical spreading depression prior to the occurrence of seizure waves induced by GABA antagonists, while the burst activity could not be observed during seizure activity. These results indicate that the cortical spreading depression-related burst activity was of antidromic origin and that the marked initial segment-somatodendritic break in spontaneous spikes of locus coeruleus neurons during cortical spreading depression was due to reduced excitability of the somatodendritic membrane. The cortical spreading depression-related burst activity may cause release of a large amount of noradrenaline in vast regions of locus coeruleus terminal fields through the numerous axon collaterals, thereby playing a role in functional changes of brain neurons related to cortical spreading depression.

Animals↗

PubMed1988

Synchronous bursting of locus coeruleus neurons in tissue culture.

Synchronous bursts of firing of locus coeruleus neurons have been observed in unanesthetized rats, particularly in response to various sensory stimuli. In explant tissue cultures, synchronous bursting activity of locus coeruleus neurons was also observed and the possible mechanisms responsible for this synchronous activation have been investigated. Barrages of depolarizing events apparently initiated and continued throughout spontaneous bursts of spikes in the cultured neurons. Simultaneous intracellular recordings from pairs of neurons show a very high degree of synchrony of such barrages between cells. On the basis of tests for electrical coupling in simultaneously recorded cell pairs, and tests for dye coupling with Lucifer Yellow, it was concluded that the synchrony is not due to electrical coupling of locus coeruleus neurons. Small non-synaptic interactions between cell pairs that may reflect elevated extracellular potassium levels have been observed on some occasions. Spontaneous and evoked depolarizations similar to those initiating the bursts appear to be synaptically mediated events, suggesting that locus coeruleus neurons are synchronously activated by a common excitatory input. It was concluded that the neurons providing this common excitation are located within or very close to the locus coeruleus, at least at birth. The synchronization of activation of many locus coeruleus neurons could result in almost simultaneous release of neurotransmitter in the widespread target areas of locus coeruleus projections.

Animals↗

PubMed2005

Increased volume of the pigmented neurons in the locus coeruleus of schizophrenic subjects: a stereological study.

The locus coeruleus is the largest cluster of noradrenaline-producing neurons in the brain and has been involved in regulating attention. The neurotransmitter system contributes to the initiation and maintenance of forebrain activity as well as modulation of the collection and processing of sensory information. This makes locus coeruleus a target of interest in the study of possible structural changes in the brains of subjects with chronic schizophrenia. Uniform sampling and optical disectors were used for estimation of total neuron numbers and the rotator principle for estimation of mean cell volume. This study estimated the bilateral total number of pigmented neurons in the locus coeruleus of schizophrenic and control subjects and found no difference between the two; schizophrenic subjects have 37,400 (coefficient of variation=CV=SD/mean=0.28), control subjects have 35,500 (CV=0.19), p=0.64. The average volume of the cell perikaryon of pigmented neurons was measured in both groups and showed a significant larger cell volume in the locus coeruleus of schizophrenic compared to control subjects; mean locus coeruleus cell volume was 58,400 microm(3) (CV=0.31) in schizophrenic subjects, which is 55% larger than the 37,600 microm(3) (CV=0.33) found in control subjects, a difference of 20,800 microm(3) (p=0.009). The fixation time was significantly longer for the schizophrenic brains with an average of 169 months compared to 88 months for the control brains. No relation was found between total numbers or geometric mean volume of the pigmented cells and fixation time.

Adult↗

PubMed1998

The biphasic effects of locus coeruleus noradrenergic activation on dendrodendritic inhibition in the rat olfactory bulb.

Some forms of olfactory learning require intact noradrenergic terminals in the olfactory bulb that originate from the locus coeruleus. To clarify the action of noradrenergic inputs on the dendrodendritic interaction between mitral and granule cells in the rat olfactory bulb, we analyzed field potentials in the granule cell layer of the olfactory bulb evoked by paired-pulse stimulation of the lateral olfactory tract before and after the activation of the locus coeruleus. Locus coeruleus activation by glutamate injection in the vicinity of the nucleus changed only the test response without any effect on conditioning response. Paired-pulse inhibition measured from the ratio of test response amplitude to conditioning response amplitude was significantly depressed immediately after locus coeruleus activation. Conversely, 2 min later, paired-pulse inhibition was significantly potentiated. The significant potentiation of inhibition lasted for several minutes. The depression-potentiation sequence of paired-pulse inhibition was blocked by infusion of timolol, a beta-antagonist, into the olfactory bulb, in a dose-dependent manner, but not by infusion of phentolamine, an alpha-antagonist. Infusion of isoproterenol, a beta-agonist, into the bulb mimicked the depression of paired-pulse inhibition by locus coeruleus activation. These results suggest that glutamate activation of the locus coeruleus produces a depression-potentiation sequence in granule cell-mediated feedback inhibition onto mitral cells in the olfactory bulb through beta-adrenergic receptors.

Adrenergic alpha-Antagonists↗

PubMed1997

Locus coeruleus activation by colon distention: role of corticotropin-releasing factor and excitatory amino acids.

The present study was designed to elucidate the neurotransmitters involved in activation of the noradrenergic nucleus, locus coeruleus, by distention of the distal colon. Locus coeruleus spontaneous discharge rate was recorded from halothane-anesthetized rats before, during and after distention of the colon produced by inflation of a balloon catheter with varying volumes of water. Locus coeruleus activation by colon distention was volume-dependent and reversible. Activation of cortical electroencephalographic activity was temporally correlated with locus coeruleus activation during colon distention and prolonged distention (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and cortical electroencephalographic activation. The corticotropin-releasing factor antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or microinfused into the locus coeruleus (10 ng) significantly attenuated locus coeruleus activation produced by lower, but not higher magnitudes of colon distention, implicating corticotropin-releasing factor afferents to the locus coeruleus in this response. Consistent with this, prior exposure to 30 min of footshock stress, which desensitizes locus coeruleus neurons to corticotropin-releasing factor, produced a similar attenuation of locus coeruleus activation by low, but not high magnitudes of distention. Kynurenic acid, administered intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus activation by all magnitudes of colon distention. However, this excitatory amino acid antagonist was ineffective when administered directly into the locus coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of colon distention activate the locus coeruleus-noradrenergic system via corticotropin-releasing factor release within the locus coeruleus and that excitatory amino acid neurotransmission at a site distal to the locus coeruleus is necessary for this response. Activation of the locus coeruleus-noradrenergic system during colon distention may serve as a cognitive limb of the peripheral parasympathetic response. This activation may also play a role in disorders characterized by comorbidity of colonic and psychiatric symptoms, such as irritable bowel syndrome.

Animals↗

PubMed1991

Monoaminergic interaction in the central nervous system: a morphological analysis in the locus coeruleus of the rat.

The locus coeruleus of the rat is richly innervated by many aminergic neurons varying in amine content and in site of origin. There are adrenergic and noradrenergic neurons originating in the medulla oblongata, dopaminergic from the hypothalamus, serotonergic from the mesencephalon and also intrinsic noradrenergic neurons in the locus coeruleus complex. Of these, adrenergic and dopaminergic inputs appear relatively specific and powerful.

Animals↗

PubMed1976

The involvement of noradrenaline in motor activity as shown by rotational behaviour after unilateral lesions of the locus coeruleus.

Unilateral electrolytic lesions in the region of the locus coeruleus in rats result in contraversive circling behaviour following the administration of systemic apomorphine or dexamphetamine. In a large group of such animals there was a very good correlation between histological damage to the locus coeruleus and the presence of such rotation. There was a progressive increase in the percentage of rats showing this drug-induced behaviour as ipsilateral cerebral cortical noradrenaline content decreased. Unilateral injections of 6-OHDA produce more selective damage to the noradrenergic locus coeruleus and result in a similar, although less marked, apomorphine- and dexamphetamine-induced rotation. Unlike the rats with electrolytic lesions of the locus coeruleus, those with 6-OHDA injections did not show an increase in ipsilateral striatal dopamine content. It seems likely that the motor asymmetry seen with lesions which involve the locus coeruleus is due to damage to its noradrenergic cells. A possible explanation of the differences between electrolytic and 6-OHDA induced lesion is that the 6-OHDA produces damage to the ventral noradrenergic bundle as well as the locus coeruleus and results in an increase in ipsilateral cerebral cortical 5-hydroxytryptamine.

Animals↗

PubMed2002

The interaction between the locus coeruleus and dorsal raphe nucleus studied with dual-probe microdialysis.

The interaction between the locus coeruleus and dorsal raphe nucleus was investigated by means of dual-probe microdialysis in conscious rats. The release of noradrenaline and 5-hydroxytryptamine (5-HT) after inhibition or stimulation of locus coeruleus and dorsal raphe activity was sampled in both nuclei and analysed by high-pressure liquid chromatography (HPLC). The inhibition of locus coeruleus activity by the infusion of the alpha(2)-adrenoceptor agonist clonidine (100 microM) decreased the release of noradrenaline to 20% in the locus coeruleus and 30% in the dorsal raphe, whilst the release of 5-HT decreased to 80% of control in the two brain areas. The excitation of locus coeruleus activity by the muscarinic receptor agonist carbachol (100 microM) led to an increase in the release of noradrenaline to 240% and 220% of control in the locus coeruleus and dorsal raphe, respectively. The release of 5-HT in both nuclei did not respond to the carbachol infusion into the locus coeruleus. Infusion of the 5-HT(1A) receptor agonist flesinoxan into the dorsal raphe (1 microM) significantly decreased the release of 5-HT in the dorsal raphe and locus coeruleus to 45% and 65% of control, respectively. The release of noradrenaline was decreased in the dorsal raphe to 45% by flesinoxan, whereas no changes were seen in the release of noradrenaline in the locus coeruleus. In conclusion, the innervation of the dorsal raphe by the locus coeruleus has a slight excitatory effect on the release of 5-HT in the dorsal raphe. The dorsal raphe does not exert a direct inhibitory influence on the release of noradrenaline in the locus coeruleus. Finally, the release of noradrenaline in the dorsal raphe may be locally regulated by 5-HT(1A) receptors.

Animals↗

PubMed1989

Blockade of alpha 2-adrenergic receptors, but not blockade of gamma-aminobutyric acidA, serotonin, or opiate receptors, augments responsiveness of locus coeruleus neurons to excitatory stimulation.

Previous studies in this laboratory indicated that alpha 2-adrenergic receptors in the locus coeruleus play a major role in regulating the responsiveness of neurons in the locus coeruleus to excitatory influences. The present study points to the possibility that alpha 2-receptors are unique among inhibitory receptors in the locus coeruleus in regulating responsiveness of these neurons independently of the spontaneous firing rate. In the first part of the study, blockade of alpha 2-receptors was shown to markedly augment responsiveness of neurons in the locus coeruleus to the excitatory stimulus of compression of the contralateral hind paw at doses of an alpha 2-blocker both above and well below those necessary to increase spontaneous activity of neurons in the locus coeruleus. In contrast, blockade of gamma-aminobutyric acid and serotonin receptors augmented spontaneous firing rates of neurons in the locus coeruleus but failed to augment responsiveness of these neurons to compression of the hindpaw. Blockade of opiate receptors failed to increase either spontaneous firing rates or the responsiveness of neurons of the locus coeruleus to paw compression; moreover, in animals given an opiate agonist over a number of days to produce tonic stimulation of opiate receptors, blockade of opiate receptors augmented spontaneous firing rates of neurons in the locus coeruleus but had no effect on responsiveness to paw compression. In that blockade of each type of inhibitory receptor tested increased the spontaneous firing rates of neurons in the locus coeruleus but only blockade of alpha 2-receptors increased the responsiveness of neurons in the locus coeruleus to stimulation, without affecting the spontaneous firing rate, alpha 2-receptors may be unique among inhibitory receptors in independently regulating the responsiveness of neurons in the locus coeruleus. One possibility discussed for why alpha 2-receptors regulate the responsiveness, independently of the spontaneous firing rate, is that there are two types of alpha 2-receptors in the locus coeruleus, one of which regulates responsiveness and another which regulates the spontaneous firing rate.

Adrenergic alpha-Antagonists↗

PubMed1985

The mechanism of cerebrovascular vasoconstriction in response to locus coeruleus stimulation.

Stimulation of the locus coeruleus in 11 Macaca nemestrina monkeys resulted in a frequency-dependent increase in internal carotid resistance (vasoconstriction) and a frequency-dependent decrease in external carotid resistance (vasodilation). The internal carotid constrictor response is maximal at low frequency stimulation (5 s-1), and decreases as frequency of stimulation is increased or decreased. It is blocked by the non-specific alpha-adrenoceptor blocker phentolamine and the alpha-2 adrenoceptor blocker yohimbine, but is unaffected by the alpha-1 adrenoceptor blocker prazosin. It is concluded that the cerebral vasoconstrictor response to locus coeruleus stimulation is mediated by alpha-2 adrenoceptors.

Animals↗

PubMed1984

Dilatation in the carotid vascular territory of the cat in response to activation of cell bodies in the locus coeruleus.

Electrical stimulation of the locus coeruleus in the monkey results in a frequency-dependent vasoconstriction in the internal carotid circulation, and a frequency-dependent vasodilatation in the external carotid circulation. In the cat we have studied the extracerebral vasodilator response using electrical stimulation at appropriately high frequencies. Further investigations reported here demonstrate that 1-glutamate, a non-specific neuronal excitant, reproduces the dilator response in the cat. This clearly shows that the response to electric stimulation of the locus coeruleus, previously reported, is due to excitation of cell bodies rather than fibres of passage.

Animals↗

PubMed2000

Role of nitric oxide in rat locus coeruleus in hypoxia-induced hyperventilation and hypothermia.

The locus coeruleus modulates the ventilatory and thermoregulatory response to hypoxia and contains nitric oxide synthase. Therefore, we examined the effects of L-NAME unilaterally microinjected into the locus coeruleus on hypoxic hyperventilation and hypothermia. Ventilation and body temperature were measured before and after microinjection of L-NAME (100 nmol/0.5 microl) into the locus coeruleus, followed by hypoxia. Control rats received microinjection of D-NAME (an inactive enantiomer of L-NAME). Under normoxia, L-NAME treatment did not affect ventilation or body temperature. D-NAME did not affect hypoxia-induced hyperventilation and hypothermia. L-NAME treatment reduced the ventilatory response to hypoxia but did not affect hypoxia-induced hypothermia. These data suggest that nitric oxide in the locus coeruleus is involved in the ventilatory response to hypoxia, exercising an inhibitory modulation on the locus coeruleus neurons, but plays no role in hypoxia-induced hypothermia.

Animals↗

PubMed1985

Impulse conduction properties of noradrenergic locus coeruleus axons projecting to monkey cerebrocortex.

Antidromically driven action potentials were recorded from norepinephrine-containing locus coeruleus neurons in response to electrical stimulation of cerebrocortical and thalamic areas in anesthetized squirrel monkeys. These cells reliably conducted impulses from cortical sites of distances up to 100 mm from locus coeruleus. Monkey locus coeruleus neurons were found to exhibit several properties previously described for these cells in rat, including slow spontaneous discharge rates, characteristic impulse waveforms, antidromic activation from many target areas, a period of suppressed activity following either antidromic or orthodromic driving and responsiveness to noxious stimuli presented as subcutaneous electrical stimulation of a rear foot. However, a large population of monkey locus coeruleus neurons was found to exhibit more rapid conduction velocities than previously found for rat (e.g. approximately 34% were greater than 1 m/s), resulting in similar conduction latencies to distant target areas in the two species. This indicates that the conduction times required for locus coeruleus impulses to reach distant target areas may be conserved across different species and sizes of brains, suggesting that these latencies play an important role in the general function of the locus coeruleus system in brain and behavioral processes.

Animals↗

PubMed2005

Excitatory amino acid receptors are involved in morphine-induced synchronous oscillatory discharges in the locus coeruleus of rats.

Our previous studies demonstrated that morphine not only decreases the firing rate of locus coeruleus neurons, but that it induces synchronous oscillatory discharges in the locus coeruleus. In the present study, we examined the role of excitatory amino acid input in the mechanisms of the morphine-induced synchronous oscillation in the locus coeruleus. Using a multiple-electrode recording technique, locus coeruleus neuronal activities were recorded under halothane anesthesia in adult Sprague-Dawley rats. Among 175 locus coeruleus neurons recorded after intracerebroventricular (i.c.v.) injection of morphine (26 nmol), 88 of them exhibited both decreased firing rates and synchronous oscillatory discharges. The morphine-induced oscillation and synchrony were reversed by i.c.v. injection of the non-selective excitatory amino acid receptor antagonist kynurenic acid, the selective NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5), or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not saline vehicle. These results suggest that excitatory amino acid input contributes to the morphine-induced synchronous oscillatory activity in the locus coeruleus. The results also provide us a pharmacology tool to study the influence of blockade of the locus coeruleus synchrony on neurotransmitter release and synaptic plasticity in the locus coeruleus target areas.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1985

Retrograde labeling of locus coeruleus neurons after lesion-induced sprouting of the coeruleohippocampal projection.

Locus coeruleus axons have been observed to proliferate and reinnervate targets after the partial removal of normal locus coeruleus inputs. Sixteen weeks after a large electrolytic lesion of the septal region, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections of the dorsal area dentata resulted in the labeling of neurons of the dorsal half of the locus coeruleus. Similar injections made at earlier postlesion times failed to produce visible HRP labeling in the locus coeruleus. These observations are consistent with our previous report of the time course for the noradrenergic reinnervation of the dorsal area dentata after septal lesions. Using double-labeling techniques, we have also demonstrated that collaterals of locus coeruleus axons that originally innervated the dorsal area dentata sprout to reinnervate that region 4 months after a lesion of the septal region. Thus the homotypic compensatory proliferation of locus coeruleus projections appears to be mediated, at least in part, by a pruning effect.

Animals↗

PubMed1976

The locus coeruleus: a cytoarchitectonic, Golgi and immunohistochemical study in the albino rat.

The locus coeruleus of the adult albino rat is a clearly delimited nucleus in Nissl-stained preparations. It is surrounded by an extensive, relatively neuron-free neuropil which is not stained in reduced silver and Luxol fast blue preparations. Most if not all locus coeruleus neurons contain the enzyme dopamine-beta-hydroxylase (DBH) and are thus presumably adrenergic. Two general classes of medium-sized neuron were found in the locus coeruleus in Nissl- and DBH-stained material: multipolar and somewhat smaller fusiform cells. The nucleus was divided into dorsal and ventral parts cytoarchitectonically; the two are distinguished in that (a) fusiform rather than multipolar cells predominate in the dorsal division, (b) cells in the dorsal division are more densely packed, and (c) a majority of the cells in the dorsal division are aligned obliquely in a dorsolateral to ventromedial orientation when viewed in the frontal plane, and longitudinally (anteroposteriorly) when viewed in the horizontal and sagittal planes. The locus coeruleus contains an estimated 1643 +/- 21 neurons (+/- S.E.M.; N=12) as determined in Nissl-stained paraffin sections, and 1439 +/- 29 neurons (+/- S.E.M.; N=6) as determined in DBH-stained frozen sections. The latter estimate is less reliable because of some uncertainty about section thickness. The ventral division of the locus coeruleus has an estimated 210 +/- 11 neurons (+/- S.E.M.; N=6). In Golgi-Cox material counterstained with cresyl violet most locus coeruleus neurons could also be classified as multipolar or fusiform, the latter being somewhat smaller. Typically, both types of neuron have relatively long thin dendrites which branch once or twice and extend well beyond the limits of the nucleus into surrounding neuropil and nuclear areas, particularly the mesencephalic nucleus of the trigeminal nerve and pontine central gray. Spines, consisting of a thin stalk of variable length with a small bulb at the end or just a thin stalk, were scattered infrequently but regularly along all dendrites and a majority of the somata of both classes. Very thin locally ramifying axon-like plexuses were impregnated in several locus coeruleus neurons, as were larger (about 3 mum diameter) projecting axons. Only about 0.07% of the locus coeruleus neurons were impregnated in the Golgi-Cox material although a wide range of impregnation times and ages was used.

Animals↗

PubMed1983

Substance P excitation of rat locus coeruleus neurones.

We have made extracellular recordings from locus coeruleus neurones contained in a pontine slice preparation. The in vitro technique permits application of known concentrations of drugs in the perfusion medium. Substance P excites locus coeruleus neurones in a concentration-dependent manner. The activity of substance P was found to reside in the C terminal region of the molecule. The relative potency of substance P and related peptides suggests that the substance P receptors present within the locus coeruleus are predominately of the substance P-P type. The synthetic analogue [D-Pro2,D-Trp7.9]substance P was not found to antagonise the action of substance P on locus coeruleus neurones.

Animals↗

PubMed1988

Cerebellar cortical and nuclear afferents from the feline locus coeruleus complex.

The origin and distribution of cerebellar cortical and nuclear afferents from the locus coeruleus complex (the nucleus locus coeruleus, the nucleus subcoeruleus, the medial and lateral subdivisions of the parabrachial nucleus and the Kölliker-Fuse nucleus) have been studied by means of retrograde transport of the wheat germ agglutinin-horseradish peroxidase complex in the cat. Cerebellar cortical depositions of the tracer were made by pressure injections, while nuclear depositions were made by implanting the tracer in crystalline form. The projection is bilateral with an ipsilateral preponderance. It reaches all the cerebellar nuclei as well as vermal, intermediate and lateral parts of the cerebellar cortex. The highest cell counts were made after tracer depositions in vermal and intermediate parts of the cerebellum. The projection in the cat has a more widespread origin than previously reported. It originates mainly within the nucleus locus coeruleus and the parabrachial nucleus (especially in its lateral subdivision), but retrogradely labelled neurons were also found in nucleus subcoeruleus, the Kölliker-Fuse nucleus and the A4 cell group. The cells of origin were of different shapes, but usually had a maximum diameter of the cell body between 15 and 30 micron. Cerebellar efferent axons passing through the locus coeruleus complex were anterogradely labelled following implants in all the cerebellar nuclei, but definite terminal labelling was not observed within the nuclei of the locus coeruleus complex.

Animals↗