Pontine Cholinergic Mechanisms Modulate the Cortical Electroencephalographic Spindles of Halothane Anesthesia

1996 ◽  
Vol 84 (4) ◽  
pp. 945-954. ◽  
Author(s):  
J. C. Keifer ◽  
H. A. Baghdoyan ◽  
R. Lydic
Keyword(s):  
Molecular Mechanisms ◽  
Acetylcholine Release ◽  
Minimum Alveolar Concentration ◽  
Pontine Reticular Formation ◽  
Halothane Anesthesia ◽  
Cholinergic Mechanisms ◽  
Microdialysis Probe ◽  
Simultaneous Measurements ◽  
Waveform Amplitude ◽  
Electroencephalogram Eeg

Background Halothane anesthesia causes spindles in the electroencephalogram (EEG), but the cellular and molecular mechanisms generating these spindles remain incompletely understood. The current study tested the hypothesis that halothane-induced EEG spindles are regulated, in part, by pontine cholinergic mechanisms. Methods Adult male cats were implanted with EEG electrodes and trained to sleep in the laboratory. Approximately 1 month after surgery, animals were anesthetized with halothane and a microdialysis probe was stereotaxically placed in the medial pontine reticular formation (mPRF). Simultaneous measurements were made of mPRF acetylcholine release and number of cortical EEG spindles during halothane anesthesia and subsequent wakefulness. In additional experiments, carbachol (88 mM) ws microinjected in the the mPRF before halothane anesthesia to determine whether enhanced cholinergic neurotransmission in the MPRF would block the ability of halothane to induce cortical EEG spindles. Results During wakefulness, mPRF acetylcholine release averaged 0.43 pmol/10 min of dialysis. Halothane at 1 minimum alveolar concentration decreased acetylcholine release (0.25 pmol/10 min) while significantly increasing the number of cortical EEG spindles. Cortical EEG spindles caused by 1 minimum alveolar concentration halothane were not significantly different in waveform, amplitude, or number from the EEG spindles of nonrapid eye movement sleep. Microinjection of carbachol into the mPRF before halothane administration caused a significant reduction in number of halothane-induced EEG spindles. Conclusions Laterodorsal and pedunculopontine tegmental neurons, which provide cholinergic input to the mPRF, play a causal role in generating the EEG spindles of halothane anesthesia.

Dialysis Delivery of an Adenosine A1Receptor Agonist to the Pontine Reticular Formation Decreases Acetylcholine Release and Increases Anesthesia Recovery Time

2003 ◽  
Vol 98 (4) ◽  
pp. 912-920 ◽  
Author(s):  
Diana Tanase ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Reticular Formation ◽  
Receptor Agonist ◽  
Acetylcholine Release ◽  
Cholinergic Neurons ◽  
Pontine Reticular Formation ◽  
Behavioral Arousal ◽  
Halothane Anesthesia ◽  
Microdialysis Probe ◽  
Within Subjects ◽  
Recovery From Anesthesia

Background Adenosine modulates cell excitability, acetylcholine release, nociception, and sleep. Pontine cholinergic neurotransmission contributes to the generation and maintenance of electroencephalographic and behavioral arousal. Adenosine A(1) receptors inhibit arousal-promoting, pontine cholinergic neurons, and adenosine enhances sleep. No previous studies have determined whether pontine adenosine also modulates recovery from anesthesia. Therefore, the current study tested the hypotheses that dialysis delivery of the adenosine A(1) receptor agonist N6-p-sulfophenyladenosine (SPA) into the pontine reticular formation would decrease acetylcholine release and increase the time needed for recovery from halothane anesthesia. Methods A microdialysis probe was positioned in the pontine reticular formation of halothane-anesthetized cats. Probes were perfused with Ringer's solution (control) followed by the adenosine A(1) receptor agonist SPA (0.088 or 8.8 mm). Dependent measures included acetylcholine release and a numeric assessment of recovery from anesthesia. An intensive, within-subjects design and analysis of variance evaluated SPA's main effect on acetylcholine release and anesthetic recovery. The adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microm) was coadministered with SPA to test for antagonist blocking of SPA's effects. Results SPA significantly (P < 0.0001) decreased acetylcholine release in the pontine reticular formation and significantly (P < 0.0001) delayed recovery from anesthesia. Coadministration of SPA and DPCPX caused no decrease in acetylcholine release or delay in postanesthetic recovery. Dialysis delivery of SPA into the cerebellar cortex confirmed that the SPA effects were site-specific to the pontine reticular formation. Conclusion The results provide a novel extension of the sleep-promoting effects of adenosine by showing that pontine delivery of an adenosine A(1) receptor agonist delays resumption of wakefulness following halothane anesthesia. This extension is consistent with a potentially larger relevance of the current findings for efforts to specify neurons and molecules causing physiologic and behavioral traits comprising anesthetic states. These data support the conclusion that adenosine A(1) receptors in medial regions of the pontine reticular formation, known to modulate sleep, also contribute to the generation and/or maintenance of halothane anesthesia.

Morphine Inhibits Acetylcholine Release in Rat Prefrontal Cortex When Delivered Systemically or by Microdialysis to Basal Forebrain

2005 ◽  
Vol 103 (4) ◽  
pp. 779-787 ◽  
Author(s):  
Nadir I. Osman ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Prefrontal Cortex ◽  
Basal Forebrain ◽  
Acetylcholine Release ◽  
Sprague Dawley ◽  
Guide Cannula ◽  
Microdialysis Probe ◽  
Prefrontal Cortical ◽  
Substantia Innominata ◽  
Morphine Administration ◽  
Intravenous Morphine

Background Cortical acetylcholine originates in the basal forebrain and is essential for maintaining normal cognition and arousal. Morphine impairs these cholinergically mediated cortical functions. The current study tested the hypothesis that morphine decreases prefrontal cortical acetylcholine release by acting at the level of the basal forebrain. Methods Adult male Sprague-Dawley rats (n = 18) were anesthetized with isoflurane. One microdialysis probe was placed in the substantia innominata region of the basal forebrain and perfused with Ringer's solution (control) followed by one concentration of morphine (1, 10, 100, or 1,000 microm) or morphine (1,000 microm) plus naloxone (100 microm). A second microdialysis probe was placed in the prefrontal cortex for measuring acetylcholine. In a second series of experiments, rats (n = 6) were implanted with electrodes for recording states of arousal, a guide cannula positioned above the prefrontal cortex for inserting a microdialysis probe, and an indwelling jugular vein catheter. The effects of administering intravenous morphine (30 mg/kg) versus normal saline (0.9%) on prefrontal cortical acetylcholine release, cortical electroencephalographic power, and behavior were quantified. Results Dialysis delivery of morphine to the substantia innominata caused a concentration-dependent, naloxone-sensitive decrease in acetylcholine release within the prefrontal cortex. The maximal decrease in acetylcholine was 36.3 +/- 11.5%. Intravenous morphine administration significantly decreased cortical acetylcholine release, increased electroencephalographic power in the 0.5- to 5-Hz range, and eliminated normal wakefulness. Conclusion Morphine causes obtundation of arousal and may cause cognitive impairment by acting at the level of the substantia innominata to disrupt cortical cholinergic neurotransmission.

scholarly journals Adenosine A1 Receptors in Mouse Pontine Reticular Formation Depress Breathing, Increase Anesthesia Recovery Time, and Decrease Acetylcholine Release

2013 ◽  
Vol 118 (2) ◽  
pp. 327-336 ◽  
Author(s):  
George C. Gettys ◽  
Fang Liu ◽  
Ed Kimlin ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Reticular Formation ◽  
Acetylcholine Release ◽  
Adenosine A1 Receptor ◽  
Breathing Rate ◽  
Pontine Reticular Formation ◽  
Central Administration ◽  
Behavioral Arousal ◽  
Adenosine A1 Receptors ◽  
Adenosine A1 ◽  
A1 Receptor

Abstract Background: Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Methods: Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N6-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8-cyclopentylxanthine. Results: First, SPA significantly decreased respiratory rate (−18%), tidal volume (−12%), and minute ventilation (−16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Conclusions: Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

Abstract 1364: Not All Refractory Period Abbreviation Promotes Atrial Fibrillation Equally: A Comparison Between Vagal and Atrial Tachycardia Remodeled Substrates

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Grigorios Katsouras ◽  
Masao Sakabe ◽  
Kristina Lemola ◽  
Philippe Comtois ◽  
Michael Ting ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Refractory Period ◽  
Atrial Tachycardia ◽  
Molecular Mechanisms ◽  
Acetylcholine Release ◽  
Autonomic Ganglia ◽  
Bipolar Electrodes ◽  
Important Contributor ◽  
Stimulation Parameters ◽  
Dominant Frequencies

Background: Vagal (VG) and atrial tachycardia remodeled (ATR) AF substrates share many features: reduced effective refractory period (ERP), increased ERP heterogeneity and some common molecular mechanisms (I KACh enhancement by acetylcholine release in VG, constitutive I KACh enhancement in ATR). This study compared VG and ATR substrates at comparable ERP abbreviation. Methods: In each of 5 VG dogs, bilateral cervical VG stimulation parameters were adjusted (mean±SD: 3.6±1.7 V and 12.2±1.5 Hz; 0.2 ms) to produce the same mean ERP (at 4 RA and 4 LA sites) as a sex and weight matched ATR dog (RA paced 400 bpm × 7 days). Mean duration of burst pacing induced AF (DAF) and local dominant frequencies (DFs, analyzed by FFT at 240 bipolar electrodes, Fig A ) were determined. Results: Mean ERP was 79±13 ms in VG and 78±13 ms in ATR dogs. DAF was greater in VG than ATR dogs (1056±323 vs 289±510 s *P<0.01; both significantly > control, 43±61 s). Despite matched ERPs, there were significant differences in DF distribution (Fig B ): DF was faster (mean DF: 11.8±1.1 Hz VG vs 9.7±1.3 Hz ATR*) and DF variability greater (indicated by SD: 1.8±0.6 Hz VG vs 0.8±0.5 Hz ATR*) in VG dogs. AF drivers reflected by maximum DF zones were adjacent to autonomic ganglia (over RA in 4/5) for VG dogs; in ATR dogs driver zones were less clear and showed variable location. Conclusions: For a comparable atrial ERP, VG AF is faster and more persistent than AF with an ATR substrate. These results are consist with modeling work suggesting that VG-induced hyperpolarization is an important contributor to AF-maintaining rotor stabilization and acceleration, and indicate important differences between these superficially similar AF substrates.

scholarly journals Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction

2021 ◽  
Vol 22 (9) ◽  
pp. 4611
Author(s):  
Ellya Bukharaeva ◽  
Venera Khuzakhmetova ◽  
Svetlana Dmitrieva ◽  
Andrei Tsentsevitsky
Keyword(s):  
Neuromuscular Junction ◽  
Neurodegenerative Diseases ◽  
Acetylcholine Receptors ◽  
Molecular Mechanisms ◽  
Acetylcholine Release ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Adrenergic Agents ◽  
Cholinergic Synaptic Transmission

Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.

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