The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat

doi:10.1016/0006-8993(89)90369-7

Brain Research

Volume 484, Issues 1–2, 10 April 1989, Pages 268-272

https://doi.org/10.1016/0006-8993(89)90369-7 Get rights and content

Abstract

The present study investigates the role of the two putative amine transmitters (norepinephrine and serotonin) in mediating the facilitatory action following locus coeruleus (LC) stimulation on hindlimb flexor and extensor monosynaptic reflexes (MSRs) in unanesthetized, decerebrate cats. When administered sequentially, in either order, methysergide (a serotonergic blocker) and prazosin (an α₁-adrenergic blocker) were observed to cause suubtotal decremental changes in the potentiation of gastrocnemius-soleus and common peroneal MSRs by stimuli applied in the LC. These changes were determined to be independent of the blood pressure changes induced by the aminergic blockers. These results support the hypothesis that the facilitation of the group Ia reflex transmission in cat spinal cord by stimulation of LC is mediated in part by α₁-noradrenergic and serotonergic mechanisms.

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2013, Current Biology
Citation Excerpt :
The noradrenergic system has long been considered important in controlling muscle tone. Stimulation of brainstem noradrenergic cells (e.g., LC cells) in anaesthetized or decerebrate animals can facilitate motoneuron activity by a α1-receptor-mediated mechanism [6, 7, 16–18]. Although this shows the noradrenergic system modulates muscle tone, it does not demonstrate that it promotes motor activity during actual behaviors.
Appropriate levels of skeletal muscle tone are needed to support routine motor behaviors. But, the brain mechanisms that function to couple muscle tone with waking behaviors are unknown. We addressed this question by studying mice with cataplexy—a condition caused by a decoupling of motor and arousal behaviors. Cataplexy is characterized by involuntary loss of muscle tone during wakefulness, which results in postural collapse during otherwise normal consciousness. Cataplexy is caused by loss of hypocretin (orexin) cells, but it is unknown how this loss triggers motor inactivity during cataplexy. Here, we used hypocretin knockout mice to identify the neurochemical cause of cataplexy and to determine the biochemical mechanisms that normally function to couple arousal and motor systems.
Using genetic, behavioral, electrophysiological, and pharmacological approaches, we show that the noradrenergic system acts to synchronize motor and arousal systems. Specifically, we show that an excitatory noradrenergic drive maintains postural muscle tone during wakefulness by activating α₁ receptors on skeletal motoneurons. Loss of this normal excitatory drive triggers motor inactivity during cataplexy by reducing motoneuron excitation. However, loss of this drive does not affect arousal since mice remain awake during cataplexy, suggesting the noradrenergic system is not required for maintaining wakefulness. Artificial restoration of noradrenergic drive to motoneurons prevents motor inactivity and rescues cataplexy.
We conclude that hypocretin deficiency causes cataplexy by short-circuiting the noradrenergic drive to skeletal motoneurons. We suggest that the noradrenergic system functions to couple the brain systems that control postural muscle tone and behavioral arousal state.
Projections from the rat cuneiform nucleus to the A7, A6 (locus coeruleus), and A5 pontine noradrenergic cell groups
2013, Journal of Chemical Neuroanatomy
Citation Excerpt :
Thus, it is possible that increased blood pressure associated with activation of neurons in the CnF (Lam and Verberne, 1997; Verberne, 1995; Verberne et al., 1997) could be mediated, only in part, by activation of the rostral LC. Finally, there is extensive anatomical (Clark and Proudfit, 1991a, 1992; Clark et al., 1991; Commissiong et al., 1978; Proudfit and Clark, 1991; Sluka and Westlund, 1992; Westlund et al., 1983) and electrophysiological evidence (Chan et al., 1986; Fung and Barnes, 1987; Fung et al., 1991, 1994; Lai et al., 1989; Strahlendorf et al., 1980) that caudal LC neurons regulate the excitability of somatic motoneurons in the spinal cord ventral horn. Indeed, future studies are needed to evaluate behavioral roles of presented minor pathway from CnF to LC neurons.
Stimulation of neurons in the cuneiform nucleus (CnF) produces antinociception and cardiovascular responses that could be mediated, in part, by noradrenergic neurons that innervate the spinal cord dorsal horn. The present study determined the projections of neurons in the CnF to the pontine noradrenergic neurons in the A5, A6 (locus coeruleus), and A7 cell groups that are known to project to the spinal cord. Injections of the anterograde tracer, biotinylated dextran amine in the CnF of Sasco Sprague-Dawley rats labeled axons located near noradrenergic neurons that were visualized by processing tissue sections for tyrosine hydroxylase-immunoreactivity. Anterogradely labeled axons were more dense on the side ipsilateral to the BDA deposit. Both A7 and A5 cell groups received dense projections from neurons in the CnF, whereas locus coeruleus received only a sparse projection. Highly varicose anterogradely labeled axons from the CnF were found in close apposition to dendrites and somata of tyrosine hydroxylase-immunoreactive neurons in pontine tegmentum. Although definitive evidence for direct pathways from CnF neurons to the pontine noradrenergic cell groups requires ultrastructural analysis, the results of the present studies provide presumptive evidence of direct projections from neurons in the CnF to the pontine noradrenergic neurons of the A7, locus coeruleus, and A5 cell groups. These results support the suggestion that the analgesia and cardiovascular responses produced by stimulation of neurons in the CnF may be mediated, in part, by pontine noradrenergic neurons.
Spinal cord and parkinsonism: Neuromorphological evidences in humans and experimental studies
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These anatomical evidences could give further support to a spinal origin of pain and autonomic failure in PD. Respect to spinal motor system, NA facilitates the induction, by glutamatergic cortical afferents, of the excitatory postsynaptic potentials (EPSPs) in motoneurons (Fung and Barnes, 1986; Lai et al., 1989; Fung et al., 1991; Palmeri et al., 1999). However, NA increases the firing of inhibitory interneurons in different brain areas, including amygdala (Kaneko et al., 2008), hippocampus (Zsiros and Maccaferri, 2008) or entorinal cortex (Lei et al., 2007) as well as in spinal cord sensitive interneurons (Gassner et al., 2009).
The involvement of the spinal cord in parkinsonism is becoming more and more evident based on human autopsies and on experimental models, obtained using specific neurotoxins or genetic manipulations. Besides Parkinson disease, other degenerative disorders characterized by parkinsonism, involve the spinal cord, and multiple neurotransmitters, apart dopamine, are altered in parkinsonism, also in their spinal projections. In the present review we discuss spinal cord pathology of different genetic or toxic experimental models of parkinsonism, as well as the neuropathological reports from autoptic cases of sporadic Parkinson disease and of other neurodegenerative conditions, overlapping with parkinsonism. Furthermore, anatomical distribution of alpha-synuclein in the spinal cord and coeruleo-spinal projections are reviewed, at the light of their possible involvement in spinal neurons degeneration. All these evidences call for an anatomical stemmed novel approach to understand specific features of parkinsonism, which might be due to such an involvement of the spinal cord. Moreover they suggest a common neurodegenerative process, underlying distinct neurodegenerative disorders, to which spinal neurons could be the more sensible.
Pain as a stressor: Effects of prior nociceptive stimulation on escape responding of rats to thermal stimulation
2010, European Journal of Pain
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A variety of stressors activate the limbic system, the hypothalamic-pituitary-adrenal axis (HPA) and the brain stem (Herman et al., 1996), resulting in descending modulation of nociceptive reflexes (Amit and Galina, 1986) and generating the impression that stress reduces pain sensitivity (Ford and Finn, 2008; Millan, 2002). However, descending modulation can influence motor output (Holmqvist and Lundberg, 1959; Lai et al., 1989; Taylor et al., 1997; Zemlan et al., 1983). Therefore, reflex suppression following stress may represent suppression of motor output rather than attenuation of pain sensations.
In our previous studies, psychological stress was shown to enhance operant escape responding of male and female rats. The stressors that produced hyperalgesia were physical restraint and social defeat. Nociceptive input also elicits stress reactions, generating the prediction that pain would facilitate pain under certain circumstances. For example, the usual method of evaluating stress in laboratory animals is to test for effects after termination of the stressor. Accordingly, operant escape performance of male and female rats was evaluated during two successive trials involving nociceptive thermal stimulation. The intent was to determine whether nociceptive sensitivity differed on first trials and during pain-induced stress on second trials. Compared to a first trial of 44.5 °C stimulation, escape responding increased during a second trial of 44.5 °C stimulation (preceded by an escape trial of 10 °C). Similarly, escape from cold (10 °C) was enhanced when preceded by escapable 44.5 °C stimulation. Thus, prior nociceptive stimulation enhanced escape from aversive thermal stimulation. Facilitation of pain by a preceding pain experience is consistent with stress-induced hyperalgesia and contrasts with other models of pain inhibition by concurrent nociceptive stimulation.
Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: An animal model of motor disorders in sleep
2008, Neuroscience
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Anatomically, the VMPJ is one of the major sources of projections to the caudal brainstem muscle inhibitory areas, the NMC (Luppi et al., 1988; Lai et al., 1999a) and the PIA (Lai et al., 1993). Axonal fibers from the VMPJ were also found to innervate the LC (Verret et al., 2006), which has been shown to have a role in motor facilitation (Fenik et al., 2005a,b,c; Fung and Barnes, 1981, 1987; Lai et al., 1989; Liu et al., 1995; Wu et al., 1999). Activation of the VMPJ may thus activate neuronal activity in the PIA and NMC via glutamatergic mechanism and suppress LC neuronal activity through GABAergic projections.
There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.
Evidence for supraspinal nervous control of external anal sphincter motility in the cat
1998, Brain Research
The aim of this study was to investigate the role of noradrenergic descending nervous pathways in external anal sphincter motility. For this purpose, the effects of intravenously injected adrenoceptor antagonist and agonist on the tonic electrical activity of this sphincter were studied in anesthetized cats. The effects of stimulating the region of the locus coeruleus and the effects of intravenous, intracerebroventricular and intrathecal injection of the above drugs on the electromyographic responses of this muscle to pudendal nerve stimulation were also investigated. The tonic sphincteric activity and the reflex response triggered by electrically stimulating pudendal afferent nerve fibers were inhibited by α₁-adrenoceptor antagonist nicergoline and enhanced by α₁-adrenoceptor agonist phenylephrine. Stimulation of the locus coeruleus area either inhibited or enhanced the reflex responses. Intracerebroventricular and intrathecal injection of the α₂-adrenoceptor agonists, morphine and leu-enkephalin decreased the amplitude of these reflex responses. All the effects of opioids were blocked by naloxone and by spinalization performed at the cervical and lumbar levels. The direct response elicited by stimulating the sphincteric motor axons was not affected either by these drugs or by the brainstem stimulation. These results suggests the existence of a pontine neuronal network controlling the motility of the external anal sphincter via noradrenergic and opioid neurons.

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The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat

Abstract

Prog. Neurobiol.

Life Sci.

Brain Research

Brain Research

Neurosci. Lett.

Brain Research

Neuropharmacology

Neuropharmacology