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Faculty

Ralph Lydic

Ralph LydicRalph Lydic
Robert H. Cole Professor
Ph.D., Texas Tech University

Email: rlydic@utk.edu
Phone (865) 974-3740

Key words: Neurochemistry, states of consciousness, pain, regulation of respiration


Research Interests

My research program aims to help understand the cellular and neurochemical mechanisms regulating states of consciousness and state-dependent changes in physiology.

Research statement

The goals of Lydic's research are elucidating the mechanisms by which sleep, opioids, and volatile anesthetics modulate pain and depress breathing and arousal.  The evolutionary perspective and current data support the view that neurons generating sleep and wakefulness preferentially modulate the ability of opioids, hypnotics, and anesthetics to alter pain, behavioral affect, and states of waking consciousness.

  • Past President, North American Sleep Research Society
  • Julien F. Biebuyck Endowed Professor of Anesthesia, The Pennsylvania State University, College of Medicine
  • Bert La Du Endowed Professor of Anesthesiology, University of Michigan
  • Distinguished Alumni Award, Graduate School of Biomedical Sciences, Texas Tech University
  • Excellence in Research Award, American Society of Anesthesiologists
  • Chairman of the External Advisory Council for the National Space Biomedical Research Institute (NSBRI), Houston, TX
  • Chairman, Advisory Panel, Institute of Circulatory and Respiratory Health, Canadian Institute of Health
  • Robert H. Cole Endowed Professor of Neuroscience Associate Chair for Research, Anesthesiology, Professor of Anesthesiology and Psychology Joint Faculty, Oak Ridge National Laboratory, University of Tennessee, Knoxville, TN

Current

  • National Heart, Lung, and Blood Institute Grant #1 R01 HL065272, "Cholinergic Phenotype in Murine Models of Sleep," Project Years 09-12, 1 July 2011 to 30 June 2014; no-cost extension to 30 June 2015; Direct Costs, $900,000; Total Costs, $1,389,268; Co-Investigator (20% effort)

Completed

  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881). Competing Renewal Application 2012 scored at 13th percentile.  NHLBI funded to 11th the percentile.
  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881). Competing Renewal Application funded 01 December 2006 through 31 December, 2011.  Award total $1,880,086.
  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881; 01-03).  1 July 1989 through June, 1992.  Direct cost amount approved before N.I.H. financial adjustments:  $334,453.00 Keifer, J. C. (P.I.),
  • Lydic, R. (Research Mentor) Parker B. Frances Fellowship Program.  Foundation for Anesthesia Education and Research.  Young Investigator Award (J. C. Keifer) September 1991 to 31 August 1992:  $66,000.
  • Lydic, R. (P.I.)  Small Instrumentation Grant Program.  Heart, Lung, and Blood Institute of N.I.H. (1-S15-HL-47749).  $13,641 for CCD Imaging System.
  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881; 04-07). Competing Renewal Application, Funded, July 1992 through April, 1996.
  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881; 08-11). Competing Renewal Application,
    Funded 1 April 1996 through 30 April 2000.  Direct cost amount approved before Congressionally directed financial adjustments: $835,651.
  • Lydic, R. (P.I.)  Opioid-induced REM sleep inhibition.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-57120).  Funded 1 August 1997 through 2001.  Direct cost amount approved before Congressionally directed financial adjustments: $704,594. 
  • Lydic, R. (Collaborating Investigator); J.K. Shoemaker (P.I.) Dean's Feasibility Grant 1998-1999:  Interstitial Acetylcholine in Human Skeletal Muscle. Division of Cardiology, Department of Medicine, The Pennsylvania State University, College of Medicine. $25,000.
  • Lydic, R. (P.I.)  Cholinergic phenotype in murine models of sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-65272).  Funded 30 September 1999 through 31 August 2003.  Award total $983,480.
  • Lydic, R. (P.I.)  Cholinergic mechanisms of breathing during sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-40881). Competing Renewal Application funded 01 April 2000 through 31 March, 2006.  Award total $1,468,529.
  • Lydic, R. (P.I.)  Opioid-induced REM sleep inhibition.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-57120).  Competing Renewal Application funded 1 July 2001 through 30 June 2006.  Award total $1,788,265.
  • Lydic, R. (P.I.)  Cholinergic phenotype in murine models of sleep.  Heart, Lung, and Blood Institute of N.I.H. (R01 HL-65272).  Competing Renewal Application funded 1 September 2003 through 31 August 2007.  Award total $1,088,558.
  • Lydic, R. (P.I.) Microdialysis delivery of Eszopiclone, Diazepam, and Zolpidem to rat pontine reticular formation effects on acetylcholine release, EEG power, breathing and arousal.  November 2007 through November 2008.  Sepracor Pharmaceutical.
  • Lydic, R. (P.I.)  Sleep: Neurobiology, Medicine and Society.  University of Michigan Sleep Class.  Education Grant number 31019 from Sanofi-Aventis USA, 4 June 2009 to 9 Sept 2009

Zhang H, Wheat H, Wang P, Jiang S, Baghdoyan HA, Neubig R, Shi X-Y, Lydic R.  RGS proteins and Gαi2 modulate sleep, wakefulness, and disruption of sleep/wake states after isoflurane and sevoflurane anesthesia.  SLEEP 39: 393-404, 2016. PMID:26564126

Garrity AG, Botta S, Lazar SB, Swor E, Vanini G, Baghdoyan HA, Lydic R. Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat. Sleep 38: 73-84, 2015.

Filbey W, Sanford D, Koch LG, Britton SL, Baghdoyan HA, Lydic, R. Dexmedetomidine and eszopiclone depress ventilation in obese rats that have features of metabolic syndrome. Sleep 37: 871-880, 2014.

Hambrecht-Wiedbusch V, Mitchell MF, Firn KA, Baghdoyan HA, Lydic R. Benzodiazepine receptor agonists differentially alter acetylcholine levels in rat amygdala. Anesthesia and Analgesia 118:1293-300, 2014.  PMC4054928

Vanini G, Nemanis K, Baghdoyan HA, Lydic R.  GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation. European Journal of Neuroscience 40: 2264-2273, 2014. PMID:24674578

Watson SL, Watson CJ, Baghdoyan HA, Lydic, R.  Adenosine A1 receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin. Neuroscience 275: 531-539, 2014.

Gettys GC, Liu F, Kimlin E, Baghdoyan HA, and Lydic R. Adenosine A1 receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release. Anesthesiology 118: 327-336, 2013.  PMCID: PMC3553235

Janda A, Lydic R, Welch KB, Brummett CM.  Thermal hyperalgesia after sciatic nerve block in rat is transient and clinically insignificant.  Regional Anesthesia and Pain Medicine. 38: 151-154, 2013.  PMID:23386052.

Wathen AB, West ES, Lydic R, Baghdoyan HA.  Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse prefrontal cortex. Sleep 35: 315-323, 2012. PMCID: PMC3274332

Pal D, Walton M, Lipinski B, Lydic R, Koch LG, Britton SL, Mashour GA.  Determination of minimum alveolar concentration for isoflurane and sevoflurane in a rodent model of human metabolic syndrome.  Anesthesia and Analgesia 114: 297-302, 2012. PMCID: PMC3272881

Vanini G, Lydic R, Baghdoyan HA.  GABA-to-ACh ratio in basal forebrain and cerebral cortex varies significantly during sleep.  Sleep 35: 1325-1334, 2012. PMCID: PMC3443758

Vanini G, Wathen BL, Lydic, R, Baghdoyan HA.  Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during REM sleep. Journal of Neuroscience 31: 2649-2656, 2011. *(Selected for "This week in the Journal) PMCID: PMC3073841

Brummett CM, Hong E, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the analgesia duration by blocking hyperpolarization-activated cation current.  Anesthesiology 115: 836-43, 2011.  PMCID: PMC3179561

Gauthier EA, Guzick SE, Brummett CM, Baghdoyan HA, Lydic R.  Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat. Anesthesiology 115: 743-53 2011.  PMCID: PMC5197808

Watson CJ, Lydic, R, Baghdoyan HA. Glutamate and GABA in rat pontine reticular formation modulate sleep duration.  Journal of Neurochemistry 118: 571-80, 2011. PMCID: PMC3144159

Watson SL, Watson CJ, Baghdoyan HA, Lydic R. Thermal nociception is decreased by hypocretin-1 and an adenosine A1 receptor agonist microinjected into the pontine reticular formation of Sprague Dawley rat.  Journal of Pain 11: 535-544, 2010. PMCID: PMC2879477

Hambrecht-Wiedbusch VS, Gauthier EA, Baghdoyan HA, Lydic R.  Benzodiazepine receptor agonists cause drug-specific and state-specific alterations in EEG power and acetylcholine release in rat pontine reticular formation.  Sleep 33:909-18, 2010. PMCID: PMC2894433. *Selected for Editorial Focus.

Brevig HN, Watson CJ, Lydic R, Baghdoyan HA. Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness.  Sleep 33: 1285-1293, 2010. PMCID: PMC2941414

Brown E, Lydic R, Schiff ND.  General anesthesia, sleep, and coma.  New England Journal of Medicine 363: 2638-2650, 2010.  PMID: 21190458

Muncey AR, Saulles AR, Koch LR, Britton SL, Baghdoyan HA, Lydic R.  Disrupted sleep and delayed recovery from chronic peripheral neuropathy are distinct phenotypes in rat model of metabolic syndrome.  Anesthesiology 113: 1176-1185, 2010. PMCID: PMC2962768

Flint R, Chang T, Lydic R, Baghdoyan HA. GABAA receptors in the pontine reticular formation of C57BL/6J mouse modulate neurochemical, electrographic, and behavioral phenotypes of wakefulness. Journal of Neuroscience 30: 12301-12309, 2010. PMCID: PMC2952114

 

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