A neuroanatomical gradient in the pontine tegmentum for the cholinoceptive induction of desynchronized sleep signs

Baghdoyan, Helen A.; Rodrigo-Angulo, Margarita L.; McCarley, Robert W.; Hobson, J. Allan

doi:10.1016/0006-8993(87)90005-9

Cited by 205 publications

(71 citation statements)

References 32 publications

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“…4E). KA induced significant peaks of activation in the alpha and low gamma range [F ϭ 6.11 (2,6), P Ͻ 0.05], with peaks at 15 Hz (P Ͻ 0.01) and 30 Hz (P Ͻ 0.001). A graph of ERSPs was generated using 9 min of recordings taken during a 10-min KA exposure and 5 min following exposure (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Lesion of this area produced REM sleep without muscle atonia or ponto-geniculo-occipital (PGO) waves (21,26,29,33), or diminished REM sleep (24). The SubCD is most active during REM sleep (5,13), and injection of the nonspecific acetylcholine receptor agonist carbachol (CAR) or the glutamatergic receptor agonist kainic acid (KA) into this area induced a REM sleep-like state with muscle atonia (2,28,38,44). The SubCD receives afferents from several nuclei, including the pedunculopontine nucleus (PPN) (11).…”

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confidence: 99%

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Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

Simon

Kezunovic

Williams

et al. 2011

American Journal of Physiology-Cell Physiology

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The dorsal subcoeruleus nucleus (SubCD) is involved in generating two signs of rapid eye movement (REM) sleep: muscle atonia and ponto-geniculo-occipital (PGO) waves. We tested the hypothesis that single cell and/or population responses of SubCD neurons are capable of generating gamma frequency activity in response to intracellular stimulation or receptor agonist activation. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. All SubCD neurons ( n = 103) fired at gamma frequency when subjected to depolarizing steps. Two statistically distinct populations of neurons were observed, which were distinguished by their high (>80 Hz, n = 24) versus low (35–80 Hz, n = 16) initial firing frequencies. Both cell types exhibited subthreshold oscillations in the gamma range ( n = 43), which may underlie the gamma band firing properties of these neurons. The subthreshold oscillations were blocked by the sodium channel blockers tetrodotoxin (TTX, n = 21) extracellularly and N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314) intracellularly ( n = 5), indicating they were sodium channel dependent. Gamma frequency subthreshold oscillations were observed in response to the nonspecific cholinergic receptor agonist carbachol (CAR, n = 11, d = 1.08) and the glutamate receptor agonists N-methyl-d-aspartic acid (NMDA, n = 12, d = 1.09) and kainic acid (KA, n = 13, d = 0.96), indicating that cholinergic and glutamatergic inputs may be involved in the activation of these subthreshold currents. Gamma band activity also was observed in population responses following application of CAR ( n = 4, P < 0.05), NMDA ( n = 4, P < 0.05) and KA ( n = 4, P < 0.05). Voltage-sensitive, sodium channel-dependent gamma band activity appears to be a part of the intrinsic membrane properties of SubCD neurons.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

Simon

Kezunovic

Williams

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Furthermore, electrical stimulation of the SubC in the decerebrate rat (Hajnik et al, 2000) elicits bilateral muscle atonia. Application of the cholinergic agonist carbachol to this area in the cat causes, at short latency, a pharmacologically induced state virtually indistinguishable from REM sleep, including the muscle atonia component (Mitler and Dement, 1974;Baghdoyan et al, 1987;Vanni-Mercier et al, 1989;Yamamoto et al, 1990). In the rat, carbachol does not normally cause a REM-like state when injected into the SubC but a state similar to REM can be induced by application of the GABA A receptor antagonists, bicuculline and GABAzine (Boissard et al, 2002;Pollock and Mistlberger, 2003).…”

Section: Abbreviationsmentioning

confidence: 99%

“…Since brainstem acetylcholine neurons projecting to the reticular formation increase their activity levels during REM sleep (reviewed in (McCarley, 2004) we believe that CARB-E SubC reticular neurons are likely to be REM-on (muscle-atonia ON) cells. In the cat, infusion of carbachol into the SubC reliably elicits a REM-like state (Baghdoyan et al, 1987;VanniMercier et al, 1989;Yamamoto et al, 1990) but this effect has been difficult to reproduce in the rat (Gnadt and Pegram, 1986;Bourgin et al, 1995;Deurveilher et al, 1997;Boissard et al, 2002). In contrast, infusion of GABA A receptor antagonists or glutamatergic agonists into the rat SubC did lead to a REM-like state being generated (Boissard et al, 2002 Pollock andMistlberger, 2003).…”

Section: Responses To Carbacholmentioning

confidence: 99%

Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins

et al. 2006

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Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study.We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (noncholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30-90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17-42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15-25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1-4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons.SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons. Some or all carbachol-excited neurons are presumably REM-on neurons.Keywords rapid-eye-movement; whole-cell; in vitro; sublaterodorsal; hypocretin; narcolepsy NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAbbreviations ACSF Artificial cerebrospinal fluid; AHP Afterhyperpolarization; AP Action potential; CARB Carbachol; CARB-E Carbachol excited; CARB-I Carbachol inhibited; CCD Charge coupled device; ChAT Choline acetyltransferase; DAB Diaminobenzidine; DC Direct current; GABA Gammaamino-butyric acid; GAD67 glutamic acid decarboxylase 67 kDa isoform; HCN Hyperpolarization activated and cyclic nucleotide gated cation channels; IACUC Institutional Animal Care and Use committee; IR-DIC Infra-red differential interference contrast; LC locus coeruleus; LDT laterodorsal tegmental nucleus; LTS low-threshold spike; mPRF medial pontine reticular formation; nNOS neuronal nitric oxide synthase; Ox A Orexin A; PGO pontine-geniculate-occipital waves; PnC pontine nucleus caudalis; PnO pontine nucleus oralis; P waves Pontine component of PGO wave...

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“…Early pharmacological and unit recording studies suggested that ACh was important for REM sleep regulation (1,2). For example, injection of cholinergic drugs into the dorsal mesopontine tegmentum reliably induced a state very similar to natural REM sleep in cats (3)(4)(5)(6). Unit recordings from the cholinergic areas of the mesopontine tegmentum revealed cells that were active during wakefulness and REM sleep, as well as neurons active only during REM sleep (7)(8)(9)(10)(11)(12)(13).…”

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confidence: 99%

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

Dort

Zachs

Kenny

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

249

159

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Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.rapid eye movement sleep | acetylcholine | optogenetics | mesopontine tegmentum | mouse R apid eye movement (REM) sleep is tightly regulated, yet the mechanisms that control REM sleep remain incompletely understood. Early pharmacological and unit recording studies suggested that ACh was important for REM sleep regulation (1, 2). For example, injection of cholinergic drugs into the dorsal mesopontine tegmentum reliably induced a state very similar to natural REM sleep in cats (3-6). Unit recordings from the cholinergic areas of the mesopontine tegmentum revealed cells that were active during wakefulness and REM sleep, as well as neurons active only during REM sleep (7-13). Electrical stimulation of the laterodorsal tegmentum (LDT) in cats increased the percentage of time spent in REM sleep (14), and activation of the pedunculopontine tegmentum (PPT) in rats induced wakefulness and REM sleep (15). If cholinergic PPT and LDT neurons are necessary for REM sleep to occur, as the early studies suggest, then lesioning the PPT or LDT should decrease REM sleep. In cats, lesions of the PPT and LDT do disrupt REM sleep (16, 17), but lesions in rodents have had little effect on REM sleep or increased REM sleep (18)(19)(20)(21)(22). Additionally, c-fos studies have found very few cholinergic cells activated under high-REM sleep conditions. When c-fos-positive cholinergic neurons in the PPT and LDT are found to correlate with the percentage of REM sleep, they still account for only a few of the total cholinergic cells in the area (23). Juxtacellular recordings of identified cholinergic neurons in the LDT found these cells had wake and REM active firing profiles, with the majority firing the highest during REM sleep (13). These discrepancies have led to alternative theories of REM sleep regulation, where cholinergic neurons do not play a key role (18, 19, 23, 24 and reviewed in 25, 26).The PPT and LDT are made up of heterogeneous populations of cells, including distinct populations of cholinergic, GABAergic, and glutamatergic neurons (27-29). Many GABAergic neurons are active during REM sleep, as indicated by c-fos (23), and both GABAergic and glutamatergic neurons have been found with maximal firing rates during REM sleep in the LDT and medial PPT (13...

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A neuroanatomical gradient in the pontine tegmentum for the cholinoceptive induction of desynchronized sleep signs

Cited by 205 publications

References 32 publications

Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

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