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Results for “Locus Coeruleus”

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PubMed1991

Noradrenergic and locus coeruleus modulation of the perforant path-evoked potential in rat dentate gyrus supports a role for the locus coeruleus in attentional and memorial processes.

The perforant path-dentate gyrus synapse has provided a model system for functional neural plasticity in adult mammalian brain. NMDA-dependent long-term changes in neural connectivity occur at this synapse in response to high-frequency input. Norepinephrine (NE) applied exogenously or released endogenously can initiate both a short- and a long-term potentiation (LTP) of the dentate gyrus response to perforant path input. Triggering of the potentiated response depends on beta-receptor activation and does not require a high-frequency stimulus. An increase in locus coeruleus (LC) activity can initiate both short and LTP of the perforant path response, although a reduction in LC activity does not alter baseline perforant path responses. This chapter considers differences between NE modulation in vitro and in vivo, differences and similarities between NE-LTP and frequency-induced LTP, and the surprising specificity of NE effects at the perforant path synapse. Studies of NE in the dentate gyrus support a role for the LC in promoting both short- and long-term enhancement of responses to complex sensory inputs and are consistent with a role for the LC in memorial as well as attentional processes.

Animals↗

PubMed1994

Baroreceptor inhibition of the locus coeruleus noradrenergic neurons.

The locus coeruleus is involved in the regulation of blood pressure. The present study was undertaken to address the question of how the blood pressure, in turn, changes the activity of the locus coeruleus neurons via the action of baroreceptors. In chloralose- and urethane-anesthetized rats, the central cut end of the aortic depressor nerve, which does not contain chemoreceptor afferents in this species, was stimulated electrically to excite baroreceptor afferents after bilateral vagotomy and sectioning of the carotid sinus nerve. Single train-pulse stimulation of the aortic depressor nerve provoked the inhibition of ongoing activity in 48% of locus coeruleus neurons tested, but 30% of them responded by excitation with subsequent inhibition. However, when the train-pulse stimulation was repeated with a frequency of 5 Hz, which is close to that of the heartbeat in the rat, all neurons were markedly inhibited. Another series of experiments was conducted in vagotomized and carotid sinus nerve-sectioned rats with intact aortic depressor nerves. When blood pressure was elevated by an intravenous injection of a pressor agent, methoxamine or angiotensin II, or by rapid blood loading, ongoing activities of all locus coeruleus neurons tested were suppressed. In contrast, intravenously injected nitroprusside, a depressor agent, increased the activity of locus coeruleus neurons. In rats with all nerves preserved, rapid blood loading markedly inhibited the activity of these neurons. Such inhibition was partially but significantly attenuated by bilateral sectioning of the aortic depressor nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

[Changes in inhibitory responses in the spinal cord of the cat induced by stimulation of suprasegmental structures during rhythmic stimulation of the locus coeruleus].

Effects of rhythmic locus coeruleus stimulation on spinal reactions evoked by cortico-, reticulo- and vestibulospinal influences were studied in anesthetized decerebellized cats. Two-component inhibitory reactions in extensor and excitatory-inhibitory reactions in flexor motoneurons were found after the stimulation of the motor cortex or the medullary reticular formation. The locus coeruleus stimulation depressed the late component of responses in both group of motoneurons but had a less influence on the early inhibitory and excitatory components. No changes were observed in reactions evoked by vestibulospinal influences in the extensor and flexor motoneurons. Mechanisms of descending influences of locus coeruleus on spinal reactions evoked by primary afferents and supraspinal structures are discussed.

Animals↗

PubMed1998

Potent excitatory influence of prefrontal cortex activity on noradrenergic locus coeruleus neurons.

An influence of the prefrontal cortex on noradrenergic locus coeruleus neurons would have profound implications for the function of the locus coeruleus system. Although the medial prefrontal cortex does not substantially innervate the core of the nucleus locus coeruleus, evidence indicates that the medial prefrontal cortex projects to regions containing locus coeruleus dendrites; indirect medial prefrontal cortex-locus coeruleus projections are also possible. Here, we examined influences of prefrontal cortex activity on locus coeruleus firing rates by activating or inactivating the medial prefrontal cortex while recording impulse activity of locus coeruleus neurons extracellularly in anaesthetized rats. Most of our electrical stimulation experiments were conducted in rats which underwent lesions of the ascending dorsal bundle of noradrenergic fibres from the locus coeruleus to eliminate locus coeruleus projections to the prefrontal cortex, because antidromic activation of locus coeruleus from the prefrontal cortex affects even non-driven locus coeruleus neurons through collaterals. Single pulse stimulation (1 mA, 0.3-0.5 ms) of the dorsomedial (frontal region 2) or prelimbic region of the medial prefrontal cortex synaptically activated 13/16 (81%) or 16/56 (29%) locus coeruleus neurons, respectively. Train stimulation (20 Hz for 0.5 s) synaptically activated greater percentages of locus coeruleus cells, 11/12 cells (92%) for the dorsomedial prefrontal cortex, and 41/50 cells (82%) for the prelimbic cortex. No inhibitory responses in the locus coeruleus were obtained with dorsomedial prefrontal stimulation, and weak inhibition was found in 16% of locus coeruleus cells with prelimbic stimulation. Electrical stimulation of more lateral frontal cortex (Fr1 area) had no effects on locus coeruleus activity. Chemical stimulation of the dorsomedial prefrontal cortex with L-glutamate (10 or 100 mM) or D,L-homocysteic acid (10 mM) phasically activated 15/26 (55%) locus coeruleus cells, and 15/68 cells (22%) with prelimbic stimulation; such activation was sometimes followed by long-lasting oscillatory activity. No locus coeruleus cells exhibited purely inhibitory responses with chemical stimulation of any prefrontal cortex site. Inactivation of the dorsomedial or prelimbic region of the prefrontal cortex with lidocaine microinjection (2%, 180 or 300 nl) reduced locus coeruleus firing rates in 6/10 (60%) or 7/19 (37%) locus coeruleus cells, respectively. In no case did lidocaine in any prefrontal cortex site activate a locus coeruleus neuron. These results indicate that the medial prefrontal cortex provides a potent excitatory influence on locus coeruleus neurons. The fact that inactivation of the medial prefrontal cortex suppressed locus coeruleus firing indicates that the medial prefrontal cortex also provides a resting tonic excitatory influence on locus coeruleus activity.

Anesthesia↗

PubMed1997

Generators of synchronous activity of the locus coeruleus during development.

The locus coeruleus is thought to play an important role in the development of the central nervous system through a coordinated release of noradrenaline. The influence of the locus coeruleus on its diverse targets is strongly synchronized by the existence of electrical and chemical coupling between neurones, afferent supply of the nucleus from restricted sources and diffuse innervation of target areas. Extensive coupling between neonatal locus coeruleus neurones produces rhythmic synchronized electrical activity and distributes afferent synaptic activity throughout the entire nucleus. The strength of electrical coupling declines with age but appears to persist to a limited extent in the adult.

Journal Article↗

PubMed1987

Anomalous rectification in rat locus coeruleus neurons.

Rat locus coeruleus neurons recorded under current clamp conditions show anomalous rectification (AR) as indicated by a progressive decrease in slope resistance measured with hyperpolarizing current pulses of increasing amplitude. AR was most prominent at potentials more negative than the K+ equilibrium potential. AR was strongly dependent on external K+ concentration and was blocked by external Ba2+ and Cs+, and intracellular injection of acetate.

Animals↗

PubMed1990

Chronic stress-induced changes in locus coeruleus neuronal activity.

Locus coeruleus (LC) activity was assessed in rats exposed to either acute or chronic stress. After one immobilization session, the number of spontaneously active LC neurons dramatically decreased. On the other hand, repeated restraint sessions enhanced noradrenergic (NA) transmission and the inhibitory effect of clonidine (CLON) was greater on these cells than in those of controls. These results bear on the adaptive changes in the NA system following acute or chronic stress.

Action Potentials↗

PubMed1982

[Changes in the postsynaptic responses of spinal cord motor neurons against a background of rhythmic stimulation of the locus coeruleus].

Influences of locus coeruleus rhythmical stimulation on the postsynaptic reactions of spinal motoneurons were studied in chloralose anesthetized cats. IPSPs evoked by flexor reflex afferent (FRA) stimulation were inhibited, but EPSPs evoked by FRA and PSPs evoked by low-threshold muscle afferents stimulation were unchanged under these conditions. The inhibition of IPSPs disappeared in reserpine-pretreated animals. Both IPSPs and EPSPs evoked by FRA stimulation were diminished also during rhythmical stimulation of nucleus reticularis pontis oralis. However this effect was not of monoaminergic nature because it was present in reserpine-pretreated animals.

Animals↗

PubMed2001

Blockade of alpha2-adrenergic receptors markedly potentiates glutamate-evoked activity of locus coeruleus neurons.

The locus coeruleus (LC) is a small pontine nucleus with widely distributed efferents that supply the majority of norepinephrine in brain. Evidence from our laboratory has implicated alpha2-adrenergic receptors on LC neurons in regulating the magnitude of the bursting response of LC neurons to both sensory stimulation and systemically administered drugs. Sub-stimulation of alpha2-adrenergic receptors in the LC and the resulting hyper-responsiveness of LC neurons is thought to at least partially mediate depression in an animal model. The present study extends previous work in our laboratory by demonstrating that blockade of alpha2-adrenergic receptors also markedly augments the bursting response of LC neurons to locally-via microiontophoresis-applied glutamate.

Animals↗

PubMedDate not supplied

[The dynamic behavioral changes in rats after destruction of the locus coeruleus].

Destruction of locus coeruleus (LC) was conducted in adult rats (male rats of the Wistar line, 250-300 g) electrolytically or by means of 6-hydroxydopamine (6-OHDA). Behaviour of the intact animals sham-operated and of rats with destructed LC was evaluated before and every week after the operation during 5 weeks. Statistically significant alterations in the behaviour were revealed only in the initially low-active rats. These animals were characterized firstly, by low motor and exploratory activity in all tests (open field and automated devices), disturbance of the reactivity to novelty--only in one week after the operation with subsequent compensation of shifts; secondly, by low level of investigatory activity in the open field and absence of habituation to the repetitive tests--from the 21-st day after the operation.

Animals↗

PubMed1980

The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus.

Stimulation of locus coeruleus (LC) has been used to induce a noradrenergic inhibition of neurones in the rat cerebral cortex. The local application of adenosine or adenosine monophosphate by microiontophoresis in the cortex was found to produce a reduction of the evoked inhibition if the purine application was begun 20 sec before LC stimulation, but an enhancement of the inhibition if applied up to 35 sec after the LC stimulation. GABA increased the duration of LC inhibition irrespective of time of application. Adenosine and GABA showed no mutual potentiation, but norepinephrine increased the size of responses to both iontophoretic adenosine and GABA. The adenosine-norepinephrine interaction was synergistic, irrespective of the order of application. It is concluded that adenosine may act both presynaptically to inhibit, and postsynaptically to enhance the effects of noradrenergic neurone activation, the dominant effect observed depending on the temporal relationship between LC activation and adenosine application.

Adenosine↗

PubMedDate not supplied

The distribution of dopamine-beta-hydroxylase, neuropeptide Y and galanin in locus coeruleus neurons.

The locus coeruleus (LC) is composed of noradrenaline-producing neurons that project widely throughout the neuraxis. Subpopulations of LC neuron perikarya have been shown to contain neuropeptide Y (NPY) and galanin (GAL). In the major terminal fields of LC projections, the cerebral cortex, dorsal thalamus and cerebellar cortex, there are differing plexuses of dopamine-beta-hydroxylase (DBH), NPY and GAL immunoreactive axons. DBH immunoreactive plexuses are found in all areas which conform in appearance to previous demonstrations of noradrenaline localization by fluorescence histochemistry. In contrast, there are few NPY immunoreactive axons in thalamus and cerebellum, and the cortical plexus, while similar to the DBH immunoreactive plexus, is not affected by 6-hydroxydopamine treatment. Similarly, there are few GAL immunoreactive axons in either cerebral cortex, dorsal thalamus or cerebellar cortex. Transection of ascending LC axons results in accumulation of DBH but not NPY or GAL immunoreactivity proximal to the lesion. These observations indicate that NPY and GAL are distributed differently in LC neurons from noradrenaline and DBH.

Animals↗

PubMed1996

Opioid desensitization: interactions with G-protein-coupled receptors in the locus coeruleus.

In rat locus coeruleus (LC) neurons, alpha 2 adrenoceptors, mu-opioid and somatostatin receptors all activate the same potassium conductance. Chronic treatment with morphine causes a loss of sensitivity that is specific to the mu-opioid response, with no change in the alpha 2 adrenoceptor-mediated response. Acute desensitization induced by opioid, somatostatin, and alpha 2-adrenoceptor agonists was studied in brain slices of rat LC using intracellular recording. A supramaximal concentration of the opioid agonist Met5-enkephalin induced a profound homologous desensitization but little heterologous desensitization to an alpha 2-adrenoceptor agonist (UK 14304) or somatostatin. All desensitized currents showed partial recovery. A supramaximal concentration of UK14304 caused a relatively small amount of desensitization. Although little interaction was observed among inhibitory G-protein-coupled receptors, activation of an excitatory receptor had marked effects on inhibitory responses. Muscarinic agonists, which produce an inward current in LC neurons, reduced the magnitude of agonist-induced outward currents and increased both the rate and amount of opioid desensitization. Muscarinic activation did not alter desensitization of alpha 2-adrenoceptor responses. Acute desensitization shares several characteristics with the tolerance induced by chronic morphine treatment of animals.

Adrenergic alpha-Agonists↗

PubMed1999

Molecular control of locus coeruleus neurotransmission.

The locus coeruleus (LC) is the major noradrenergic nucleus in the brain and innervates large segments of the neuraxis. LC neurons are thought to regulate states of attention and vigilance as well as activity of the sympathetic nervous system. These neurons also have been implicated in the actions of stress, antidepressants, and opiates on the brain. Aided in part by the fact that the LC is relatively homogeneous, it has been possible to understand some of the cellular and molecular mechanisms that control their functional state. This review focuses on the role played by the cAMP pathway in regulation of LC neurons, particularly after chronic perturbations. Thus, several components of this intracellular signaling pathway are upregulated in the LC after chronic stress or chronic opiate treatment, but downregulated after chronic antidepressant treatment. LC neurons exhibit a pacemaker activity, which appears to be mediated, at least in part, by a nonspecific cation current that is activated by protein kinase A. As a result, stimuli that upregulate the cAMP pathway after chronic administration (e.g., stress or opiates) increase the excitability of LC neurons, whereas stimuli that downregulate the cAMP pathway (e.g., antidepressants) exert the opposite effect. Such molecular adaptations could contribute to the behavioral plasticity that is associated with these various conditions.

Antidepressive Agents↗

PubMedDate not supplied

Labyrinthine influences on locus coeruleus neurons.

The locus coeruleus (LC) complex, located in the dorsolateral pontine tegmentum, is composed principally of noradrenergic neurons, which project to broad regions of the CNS, including the spinal cord. Experiments were performed in precollicular decerebrate cats to ascertain whether units histologically identified within the LC complex, and having the physiological characteristics of noradrenergic neurons, would respond to sinusoidal stimulation of labyrinth receptors. Among 141 LC complex neurons, 16 of which could be activated antidromically by stimulation of the spinal cord at T12-L1, 80 (i.e. 56.7%) responded to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. The responses were particularly related to the extreme animal displacements, thus being attributed to stimulation of macular utricular receptors. The proportion of responsive units, and also the average gain of the responses, were higher in the LCd and the subcoerular (subLC) area than in the LCa. Moreover in the same structures the majority of units showed a beta-pattern of response (excitation during side-up tilt), which contrasted with the predominant alpha-pattern (excitation during side-down tilt) displayed by the previously recorded vestibulospinal neurons projecting to the same segments of the spinal cord. The role that the noradrenergic coeruleospinal neurons exert in the dynamic control of posture during the vestibulospinal reflexes is discussed.

Animals↗

PubMed2005

Orexins cause depolarization via nonselective cationic and K+ channels in isolated locus coeruleus neurons.

The locus coeruleus (LC) contains noradrenergic neurons that are innervated by orexin (ORX)-like immunoreactive axons and express both orexin receptor-1 and -2. We studied effects of ORX-A and -B (ORX-A/B) on dissociated LC neurons by using whole-cell patch clamp techniques. In current-clamp mode, LC neurons were depolarized by application of ORX-A (10(-7) M) [53% of neurons tested; 9.0+/-0.2 mV (n=5)], or ORX-B (10(-7) M) [38% of neurons tested; 4.0+/-0.1 mV (n=5)]. Firing frequencies of action potentials increased during application [1.1+/-0.2 Hz (n=5) in ORX-A; 0.8+/-0.2 Hz (n=5) in ORX-B] and returned to the control level [0.2+/-0.1 Hz (n=5)] after removal. The ORX-A/B-induced depolarization was well maintained in the presence of TTX (3x10(-7) M), CNQX (10(-6) M) and AP5 (10(-5) M). In voltage-clamp mode, removal of external Na+ suppressed both ORX-A/B-induced currents and shifted their reversal potentials from approximately -45 mV to -60 mV. In addition, ORX-A/B inhibited sustained K+ currents. These results suggest that ORX-A/B increase the firing frequency of LC neurons through the depolarization probably produced by both augmentation of the nonselective cationic conductance and inhibition of the sustained K+ conductance.

2-Amino-5-phosphonovalerate↗

PubMed2001

Morphine induces synchronous oscillatory discharges in the rat locus coeruleus.

The noradrenergic locus coeruleus (LC) plays a role in opioid dependence and withdrawal. In the present study, using a multiple-electrode recording technique that allowed several LC neurons to be recorded simultaneously over long time periods, LC neuronal activities were recorded before and after intracerebroventricular injection of morphine (26 nmol) under halothane anesthesia. We found that morphine did not simply decrease firing rates of LC neurons, as reported in earlier studies, but that it induced persistent oscillatory discharges in 49% (87 of 178) of the LC neurons recorded. Cross-correlation analysis revealed that almost all LC neurons (86 of 87) that exhibited oscillatory discharges were synchronized with at least one other neuron. When stated in terms of simultaneously recorded neuron pairs, 59% (292 of 492) of the oscillatory neuron pairs discharged synchronously. The morphine-induced synchronous oscillation began at approximately 10 min after morphine injection, reached its peak in approximately 20-30 min, persisted throughout the recording periods (up to 110 min after morphine injection, the longest recording time), and were reversed by an opioid receptor antagonist naltrexone. These data suggest that although the overall firing rate of LC neurons was reduced by morphine, the morphine-induced synchronous oscillatory activity may summate temporally and spatially at LC axon terminals and facilitate release of noradrenaline. Noradrenaline is an important neuromodulator and has been shown to induce and facilitate synaptic plasticity at LC target sites. We propose that the morphine-induced long-lasting synchronous oscillatory activity in the LC may be a neuronal signal that could induce synaptic plasticity leading to opioid addiction.

Action Potentials↗

PubMed2004

ATP-sensitive potassium channels and endogenous adenosine are involved in spinal antinociception produced by locus coeruleus stimulation.

The effects of locus coeruleus stimulation on nociceptive evoked discharges of thalamic parafascicular (PF) neurons were investigated in lightly urethane-anesthetized rats, aiming to study the mechanisms underlying these effects. Intrathecal (i.t.) administration of aminophylline (an adenosine antagonist), glibenclamide (an ATP-sensitive potassium [K+(ATP)] channels blocker), nicrorandil (Nico; an agonist of K+(ATP) channel and a K+(ATP) channel opener), and 5'-N-ethylcarboxamido-adenosine (NECA; an adenosine agonist) were used. The results showed that (1) locus coeruleus stimulation significantly inhibited the nociceptive evoked discharges of parafascicular neurons, (2) locus coeruleus stimulation-produced antinociception in PF neurons was blocked by both it. glibenclamide and i.t. aminophylline, (3) nociceptive discharges of PF neurons were also suppressed by both i.t. NECA and i.t. nicorandil, and (4) i.t. glibenclamide showed no effect on the suppression of nociceptive discharges induced by NECA, whereas aminophylline blocked the suppression of nociceptive discharges induced by nicorandil. These results suggest that (a) K+(ATP) channels and endogenous adenosine may be involved in the mediation of antinociception induced by norepinephrine, which is released in the dorsal horn by descending fibers originating from the locus coeruleus and (b) the opening of K+(ATP) channels may precede the release of endogenous adenosine in the process of suppressing nociceptive transmission at the spinal level.

Action Potentials↗