Sleep cycle control and cholinergic mechanisms: Differential effects of carbachol injections at pontine brain stem sites

doi:10.1016/0006-8993(75)90369-8

Brain Research

Volume 98, Issue 3, 21 November 1975, Pages 501-515

https://doi.org/10.1016/0006-8993(75)90369-8 Get rights and content

Summary

Muscular atonia and cortical desynchronization, two signs of desynchronized sleep, can be enhanced or suppressed by direct injection of carbachol into the pontine brain stem of cats. The positive effects are graded, being maximal in the gigantocellular tegmental field and less marked in adjacent nuclei. These positive effects are dose-dependent. Suppressive effects of carbachol are maximal in the region of the locus coeruleus and are dose-dependent but do not exceed those of the vehicle alone. The results support the hypothesis that cholinergic mechanisms of the pontine tegmentum are involved in desynchronized sleep generation.

References (30)

FooteS.L.
Compensatory changes in REM sleep time of cats during ad libitum sleep and following brief REM sleep deprivation
Brain Research
(1973)
HobsonJ.A.
A method of head restraint for cats
Electroenceph. clin. Neurophysiol.
(1972)
HobsonJ.A. et al.
Cortical unit activity in sleep and waking
Electroenceph. clin. Neurophysiol.
(1971)
MitlerM.M. et al.
Cataleptic-like behavior in cats after micro-injections of carbachol in pontine reticular formation
Brain Research
(1974)
SteinD. et al.
Effects of α-methyl-p-tyrosine upon cerebral amine metabolism and sleep stages in the cat
Brain Research
(1974)
AmatrudaT. et al.
The effects of carbachol injections at two brain stem sites
AmatrudaT. et al.
Cholinergic enhancement and suppression of desynchronized sleep
Soc. Neurosci. Abstr.
(1974)
BaxterB.L.
Induction of both emotional behavior and a novel form of REM sleep by chemical stimulation applied to cat mesencephalon
Exp. Neurol.
(1969)
BermanA.L.
The Brain Stem of the Cat
(1968)
BrodalA.
The Reticular Formation of the Brain Stem. Anatomical Aspects and Functional Correlations
(1957)

FredericksonC.J. et al.

Electrical stimulation of the brain stem and subsequent sleep

Arch. ital. Biol.

(1970)

GeorgeR. et al.

A cholinergic mechanism in the brainstem reticular formation: induction of paradoxical sleep

Int. J. Neuropharmacol.

(1964)

HartmannE. et al.

Intraventricular administration of neurotransmitters: effects on sleep

HobsonJ.A. et al.

Single neuron activity in cat gigantocellular tegmental field: selectivity of discharge in desynchronized sleep

Science

(1971)

HobsonJ.A. et al.

Selective firing by cat pontine brain stem neurons in desynchronized sleep

J. Neurophysiol.

(1974)

Cited by (123)

Which structure generates paradoxical (REM) sleep: The brainstem, the hypothalamus, the amygdala or the cortex?
2024, Sleep Medicine Reviews
Paradoxical or Rapid eye movement (REM) sleep (PS) is a state characterized by REMs, EEG activation and muscle atonia. In this review, we discuss the contribution of brainstem, hypothalamic, amygdalar and cortical structures in PS genesis. We propose that muscle atonia during PS is due to activation of glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD) projecting to glycinergic/GABAergic pre-motoneurons localized in the ventro-medial medulla (vmM). The SLD PS-on neurons are inactivated during wakefulness and slow-wave sleep by PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray (vPAG) and the adjacent deep mesencephalic reticular nucleus. Melanin concentrating hormone (MCH) and GABAergic PS-on neurons localized in the posterior hypothalamus would inhibit these PS-off neurons to initiate the state. Finally, the activation of a few limbic cortical structures during PS by the claustrum and the supramammillary nucleus as well as that of the basolateral amygdala would also contribute to PS expression. Accumulating evidence indicates that the activation of these limbic structures plays a role in memory consolidation and would communicate to the PS-generating structures the need for PS to process memory. In summary, PS generation is controlled by structures distributed from the cortex to the medullary level of the brain.
The cognitive neuroscience of lucid dreaming
2019, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
In general, it is known that AChEls inhibit the metabolic inactivation of ACh by inhibiting the enzyme acetylcholinesterase (AChE), leading to accumulation of ACh at synapses. Furthermore, ACh and its agonists as well as AChE and its antagonists are involved in the generation of REM sleep (Amatruda et al., 1975; Gillin et al., 1985; Velazquez-Moctezuma et al., 1991). For example, evidence suggests that REM sleep is controlled by cholinergic neurons in the brainstem (Baghdoyan, 1997; Hernandez-Peon et al., 1963), and studies have observed that microinjection of the ACh agonist carbachol in the pontine area of the brainstem results in REM sleep in both humans and animals (Amatruda et al., 1975; Baghdoyan, 1997).
Lucid dreaming refers to the phenomenon of becoming aware of the fact that one is dreaming during ongoing sleep. Despite having been physiologically validated for decades, the neurobiology of lucid dreaming is still incompletely characterized. Here we review the neuroscientific literature on lucid dreaming, including electroencephalographic, neuroimaging, brain lesion, pharmacological and brain stimulation studies. Electroencephalographic studies of lucid dreaming are mostly underpowered and show mixed results. Neuroimaging data is scant but preliminary results suggest that prefrontal and parietal regions are involved in lucid dreaming. A focus of research is also to develop methods to induce lucid dreams. Combining training in mental set with cholinergic stimulation has shown promising results, while it remains unclear whether electrical brain stimulation could be used to induce lucid dreams. Finally, we discuss strategies to measure lucid dreaming, including best-practice procedures for the sleep laboratory. Lucid dreaming has clinical and scientific applications, and shows emerging potential as a methodology in the cognitive neuroscience of consciousness. Further research with larger sample sizes and refined methodology is needed.
Circuit mechanisms and computational models of REM sleep
2019, Neuroscience Research
Citation Excerpt :
There is an ongoing debate on the functional role of the PPT/LDT in the initiation and maintenance of REM sleep. Lesion (Petrovic et al., 2013; Shouse and Siegel, 1992; Webster and Jones, 1988; Sastre et al., 1981) and pharmacological (Boissard et al., 2002; Gnadt and Pegram, 1986; Deurveilher et al., 1997; George et al., 1964; Amatruda et al., 1975; Baghdoyan et al., 1984; Coleman et al., 2004; Pollock and Mistlberger, 2005) studies have provided inconsistent and contradictory results. Recently, chemogenetic activation of PPT neurons was performed (Kroeger et al., 2017): glutamatergic activation increases the duration of wakefulness, while GABAergic activation moderately reduces the duration of REM sleep.
Rapid eye movement (REM) sleep or paradoxical sleep is an elusive behavioral state. Since its discovery in the 1950s, our knowledge of the neuroanatomy, neurotransmitters and neuropeptides underlying REM sleep regulation has continually evolved in parallel with the development of novel technologies. Although the pons was initially discovered to be responsible for REM sleep, it has since been revealed that many components in the hypothalamus, midbrain, pons, and medulla also contribute to REM sleep. In this review, we first provide an up-to-date overview of REM sleep-regulating circuits in the brainstem and hypothalamus by summarizing experimental evidence from neuroanatomical, neurophysiological and gain- and loss-of-function studies. Second, because quantitative approaches are essential for understanding the complexity of REM sleep-regulating circuits and because mathematical models have provided valuable insights into the dynamics underlying REM sleep genesis and maintenance, we summarize computational studies of the sleep-wake cycle, with an emphasis on REM sleep regulation. Finally, we discuss outstanding issues for future studies.
Challenges and opportunities for brainstem neuroimaging with ultrahigh field MRI
2018, NeuroImage
The human brainstem plays a central role in connecting the cerebrum, the cerebellum and the spinal cord to one another, hosting relay nuclei for afferent and efferent signaling, and providing source nuclei for several neuromodulatory systems that impact central nervous system function. While the investigation of the brainstem with functional or structural magnetic resonance imaging has been hampered for years due to this brain structure's physiological and anatomical characteristics, the field has seen significant advances in recent years thanks to the broader adoption of ultrahigh-field (UHF) MRI scanning. In the present review, we focus on the advantages offered by UHF in the context of brainstem imaging, as well as the challenges posed by the investigation of this complex brain structure in terms of data acquisition and analysis. We also illustrate how UHF MRI can shed new light on the neuroanatomy and neurophysiology underlying different brainstem-based circuitries, such as the central autonomic network and neurotransmitter/neuromodulator systems, discuss existing and foreseeable clinical applications to better understand diseases such as chronic pain and Parkinson's disease, and explore promising future directions for further improvements in brainstem imaging using UHF MRI techniques.
Dreaming epiphenomena of narcolepsy
2010, Sleep Medicine Clinics
State-dependent control of lumbar motoneurons by the hypocretinergic system
2010, Experimental Neurology
Neurons in the lateral hypothalamus (LH) that synthesize hypocretins (Hcrt-1 and Hcrt-2) are active during wakefulness and excite lumbar motoneurons. Because hypocretinergic cells also discharge during phasic periods of rapid eye movement (REM) sleep, we sought to examine their action on the activity of motoneurons during this state. Accordingly, cat lumbar motoneurons were intracellularly recorded, under α-chloralose anesthesia, prior to (control) and during the carbachol-induced REM sleep-like atonia (REMc). During control conditions, LH stimulation induced excitatory postsynaptic potentials (composite EPSP) in motoneurons. In contrast, during REMc, identical LH stimulation induced inhibitory PSPs in motoneurons. We then tested the effects of LH stimulation on motoneuron responses following the stimulation of the nucleus reticularis gigantocellularis (NRGc) which is part of a brainstem–spinal cord system that controls motoneuron excitability in a state-dependent manner. LH stimulation facilitated NRGc stimulation-induced composite EPSP during control conditions whereas it enhanced NRGc stimulation-induced IPSPs during REMc. These intriguing data indicate that the LH exerts a state-dependent control of motor activity. As a first step to understand these results, we examined whether hypocretinergic synaptic mechanisms in the spinal cord were state dependent. We found that the juxtacellular application of Hcrt-1 induced motoneuron excitation during control conditions whereas motoneuron inhibition was enhanced during REMc. These data indicate that the hypocretinergic system acts on motoneurons in a state-dependent manner via spinal synaptic mechanisms. Thus, deficits in Hcrt-1 may cause the coexistence of incongruous motor signs in cataplectic patients, such as motor suppression during wakefulness and movement disorders during REM sleep.

View all citing articles on Scopus

^*: Author to whom reprint requests should be addressed.

View full text

Article preview

Brain Research

Summary

References (30)

Compensatory changes in REM sleep time of cats during ad libitum sleep and following brief REM sleep deprivation

Brain Research

A method of head restraint for cats

Electroenceph. clin. Neurophysiol.

Cortical unit activity in sleep and waking

Electroenceph. clin. Neurophysiol.

Cataleptic-like behavior in cats after micro-injections of carbachol in pontine reticular formation

Brain Research

Effects of α-methyl-p-tyrosine upon cerebral amine metabolism and sleep stages in the cat

Brain Research

The effects of carbachol injections at two brain stem sites

Cholinergic enhancement and suppression of desynchronized sleep

Soc. Neurosci. Abstr.

Induction of both emotional behavior and a novel form of REM sleep by chemical stimulation applied to cat mesencephalon

Exp. Neurol.

The Brain Stem of the Cat

The Reticular Formation of the Brain Stem. Anatomical Aspects and Functional Correlations

Electrical stimulation of the brain stem and subsequent sleep

Arch. ital. Biol.

A cholinergic mechanism in the brainstem reticular formation: induction of paradoxical sleep

Int. J. Neuropharmacol.

Intraventricular administration of neurotransmitters: effects on sleep

Single neuron activity in cat gigantocellular tegmental field: selectivity of discharge in desynchronized sleep

Science

Selective firing by cat pontine brain stem neurons in desynchronized sleep

J. Neurophysiol.

Cited by (123)

Which structure generates paradoxical (REM) sleep: The brainstem, the hypothalamus, the amygdala or the cortex?

The cognitive neuroscience of lucid dreaming

Circuit mechanisms and computational models of REM sleep

Challenges and opportunities for brainstem neuroimaging with ultrahigh field MRI

Dreaming epiphenomena of narcolepsy

State-dependent control of lumbar motoneurons by the hypocretinergic system