Research Interests

Neurochemical regulation of sleep and wakefulness, mechanisms of general anesthesia, mechanisms underlying the relationship between sleep disruption and psychiatric disorders

Research statement

My research program aims to identify the neurochemical mechanisms and brain regions that regulate behavioral states such as sleep, wakefulness, and anesthesia.  The goals of my laboratory are to identify overlapping neuronal circuits regulating the interactions between sleep, anesthesia, mood, cognition, and pain.  The work focuses on acetylcholine, GABA, and hypocretin/orexin as neurotransmitters, and the pontine reticular formation, basal forebrain, and prefrontal cortex as brain regions important for behavioral state control.

• 2003      Invited Lecturer, APSS 17th Annual Meeting, 50th Anniversary of the Discovery of REM Sleep
• 2004 – 2014   MERIT Award, National Institute of Mental Health
• 2005      Department of Anesthesiology Basic Science Research Award
• 2007      Department of Anesthesiology Basic Science Research Award
• 2012      Invited Lecturer, APSS 26th Annual Meeting
• 2013      Michigan Institute for Clinical & Health Research (MICHR) Distinguished Clinical and Translational Research Mentor Award
• 2014      Beaman Professor, University of Tennessee, Knoxville

Current

• National Institute of Mental Health Grant #5 R37 MH45361, “Cholinergic Mechanisms of REM Sleep Generation,” Project Years 22-26, 1 March 2009 to 31 January 2014; no-cost extension to 31 January 2015; Direct Costs, $1,165,384; Total Costs, $1,800,519; Principal Investigator (50% effort)
• 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) [Principal Investigator: R. Lydic]

Completed

• National Institute of Mental Health Grant #5 R37 MH45361, “Cholinergic Mechanisms of REM Sleep Generation,” Project Years 17-21, 1 May 2004 to 28 February 2009; Direct Costs, $1,125,000; Principal Investigator (50% effort)
• National Institute of Mental Health Grant #2 R01 MH45361, “Cholinergic Mechanisms of REM Sleep Generation,” Project Years 06-16, 1 September 1994 to 30 April 2004; Direct Costs, $2,212,374; Principal Investigator (50% effort)
• National Institute of Mental Health (FIRST Award) Grant #1 R29 MH45361, “Cholinergic Mechanisms of REM Sleep Generation,” Project Years 01-5, 1 September 1989 to 31 August 1994; Direct Costs, $350,000, Principal Investigator (50% effort)
• National Heart, Lung, and Blood Institute Grant #R01 HL57120, “Opioid-Induced REM Sleep Inhibition,” Project Years 01-10, 1 August 1997 to 30 June 2006: Direct Costs, $1,754,493; Co-Investigator (25% effort) [Principal Investigator: R. Lydic]
• National Heart, Lung, and Blood Institute Grant #1 R01 HL065272, “Cholinergic Phenotype in Murine Models of Sleep,” Project Years 01-09, 30 September 1999 to 31 August 2007; Direct Costs, $1,385,000; Co-Investigator (25% effort) [Principal Investigator: R. Lydic]

Recent Peer Reviewed

• Blakeley-Ruiz JA, McClintock CS, Shrestha HK, Poudel S, Yang ZK, Giannone RJ, Choo JJ, Podar M, Baghdoyan HA, Lydic R, Hettich RL. Morphine administration differentially alters gut microbiome composition and metabolic function in lean vs. obese mice. ISME Comm 2, 6, 2022. https://doi.org/10.1038/s43705-022-00131-6
• Glovak ZT, Baghdoyan HA, Lydic R. Fentanyl and neostigmine delivered to mouse prefrontal cortex differentially alter breathing. Respiratory Physiology & Neurobiology 303 (103924):1-10, 2022. https://doi.org/10.1016/j.resp.2022.103924
• Glovak ZT, Angel C, O’Brien CB, Baghdoyan HA, and Lydic R. Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status. Respir Physiol Neurobiol, 297:103834, 2022. DOI:10.1016/j.resp.2021.103834
• O’Brien CB, Locklear CE, Glovak ZT, Zebadúa Unzaga D, Baghdoyan HA, Lydic R. Opioids cause dissociated states of consciousness in C57BL/6J mice. Journal of Neurophysiology 126: 1265-1275, 2021 https://doi.org/10.1152/jn.00266.2021
• Lydic R and Baghdoyan HA. Prefrontal cortex metabolome is modified by opioids, anesthesia, and sleep. Physiology 36: 203-219, 2021. https://doi.org/10.1152/physiol.00043.2020
• Ramirez J-M, Burgraff N, Wei A, Baertsch, N, Varga A, Saunders S, Baghdoyan HA, Lydic R, Morris, R, Bolser D, Levitt E. Neuronal mechanisms underlying opioid Induced respiratory depression. Journal of Neurophysiology, 2021. https://doi.org/10.1152/jn.00017.2021
• Baer AG, Bourdon AK, Price JM, Campagna SR, Jacobson DA, Baghdoyan HA, Lydic R. Isoflurane anesthesia disrupts the cortical metabolome. Journal of Neurophysiology 124: 2012-2021, 2020. https://doi.org/10.1152/jn.00375.2020
• Zhang X, Baer AG, Price J, Jones PC, Garcia BJ, Romero J, Cliff A, Mi W, Brown JB, Jacobson DA, Lydic R, Baghdoyan HA. Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia. Journal of Neurophysiology 123: 2285-2296, 2020.https://doi.org/10.1152/jn.00092.2020
• O’Brien, C.B., Baghdoyan H.A., Lydic R. Computer-based multitaper spectrogram program for electroencephalographic data. Journal of Visualized Experiments. (153), e60333, DOI: doi:10.3791/60333 (2019). URL: https://www.jove.com/video/60333
• Lu Y, Li Y-W, Wang L, Lydic R, Baghdoyan HA, Shi X-Y, Zhang H. Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials. Sleep Medicine Reviews 48:101207, 2019. https://doi.org/10.1016/j.smrv.2019.08.001
• Blakeley-Ruiz JA, McClintock CS, Lydic R, Baghdoyan HA, Choo JJ, and Hettich RL. Combining integrated systems-biology approaches with intervention-based experimental design provides a higher-resolution path forward for microbiome research. Commentary on Hooks et al., Microbiota-gut-brain research: a critical analysis. Behavioral and Brain Sciences 42, E66. 2019. doi:10.1017/S0140525X18002911
• McLain JM, Alami WH, Glovak ZT, Cooley CR, Burke SJ, Collier JJ, Baghdoyan HA, Karlstad MD, Lydic, R.  Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes.  SLEEP 41:(11) 1-9, 2018. doi:10.1093/sleep/zsy156. PMID:30107617
• Bourdon AK, Spano G, Marshall W, Bellesi M, Tononi G, Serra PA, Baghdoyan HA, Lydic R, Campagna SR, Cirelli C. Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. Scientific Reports 8(1): Article number 11225, 2018. doi:10.1038/s41598-018-29511-6
• Angel C, Glovak ZT, Alami W, Mihalko S, Price J, Jiang Y, Baghdoyan HA, Lydic R. Buprenorphine depresses respiratory variability in obese mice with altered leptin signaling. Anesthesiology 128(5):984-991, 2018. doi: 10.1097/ALN.0000000000002073
• Glovak Z, Mihalko S, Baghdoyan HA, Lydic R. Leptin status alters buprenorphine-induced antinociception in obese mice with dysfunctional leptin receptors. Neuroscience Letters 660:29-33, 2017. PMCID: PMC5651198 [Available on 2018-11-01] http://dx.doi.org/10.1016/j.neulet.2017.09.012
• Zhang H, Wheat H, Wang P, Jiang S, Baghdoyan HA, Neubig R, Shi X-Y, Lydic R.  RGS proteins and Gai2 modulate sleep, wakefulness, and disruption of sleep/wake states after isoflurane and sevoflurane anesthesia. Sleep 39(2):393-404, 2016. PMCID: PMC4712393.  doi:10.5665/sleep.5450
• 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(1):73-84, 2015. PMCID: PMC4262959
• Filbey W, Sanford D, Baghdoyan HA, Koch LG, Britton SL, Lydic R. Eszopiclone and dexmedetomidine depress ventilation in obese rats with features of metabolic syndrome. Sleep 37(5):871-880, 2014. PMCID: PMC3985114
• Hambrecht-Wiedbusch VS, Mitchell MF, Firn KA, Baghdoyan HA, and Lydic R. Benzodiazepine site agonists differentially alter acetylcholine release in rat amygdala. Anesthesia & Analgesia 118(6):1290-1300, 2014. PMCID: PMC4054928
• Vanini G, Nemanis K, Baghdoyan HA, and 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(1):2264-2273, 2014. PMCID: PMC4107042
• Watson SL, Watson CW, 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. PMCID: PMC414337.
• Gettys GG, 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(2):327-336, 2013. PMCID: PMC3553235
• Vanini G and Baghdoyan HA. Extrasynaptic GABAA receptors in rat pontine reticular formation increase wakefulness. Sleep 36(3):337-343, 2013. PMCID: PMC3571742
• Vanini G, Lydic R, Baghdoyan HA. GABA-to-ACh ratio in basal forebrain and cerebral cortex varies significantly during sleep. Sleep 35(10):1325-1334, 2012. PMCID: PMC3443758
• Wathen AB, West ES, Lydic R, and Baghdoyan HA. Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse prefrontal cortex. Sleep 35(3):315-323, 2012. PMCID: PMC3274332

Recent Invited Chapters and Reviews

• Lydic R, Baghdoyan HA, May AL. Neurochemistry of anesthetic states. In: Chemical and Biochemical Approaches to the Study of Anesthetic Function, Volume Editors: IJ. Dmochowski and RC Eckenhoff, Methods in Enzymology 603:237-255, 2018. Series Editors: AM Pyle and DW. Christianso, Elsevier, New York. https://doi.org/10.1016/bs.mie.2018.01.024 2018.
• Lydic R, Keifer JC, Baghdoyan HA, Craft R, and Angel C. Opiate action on sleep and breathing. In: Principles and Practice of Sleep Medicine, 6th Edition, edited by MH Kryger, T Roth, and WC Dement. Elsevier, New York, pp 250-259, 2017.
• Sternberg M, Baghdoyan HA, and Lydic R. A circular conundrum: Sleep disruption worsens pain and pain medications disrupt sleep.  In:  Managing Pain: Essentials of Diagnosis and Treatment, edited by CM Brummett and S Cohen.  Oxford University Press, New York, pp 164-182, 2013.
• Baghdoyan HA and Lydic R.  The neurochemistry of sleep and wakefulness.  In:  Basic Neurochemistry, edited by ST Brady, RW Albers, DL Price, and GJ Siegel.  Elsevier, pp 982-999, 2012.
• Watson CJ, Baghdoyan HA, and Lydic R. REM sleep regulation by cholinergic neurons: Highlights from 1999 to 2009.  In:  Rapid Eye Movement Sleep – Regulation and Function, edited by BN Mallick, SR Pandi-Perumal, RW McCarley, and AR Morrison, Cambridge University Press, pp 194-205, 2011.
• Vanini G, Lydic R, and Baghdoyan HA. GABAergic modulation of REM sleep.  In:  Rapid Eye Movement Sleep – Regulation and Function, edited by BN Mallick, SR Pandi-Perumal, RW McCarley, and AR Morrison, Cambridge University Press, pp 206-213, 2011.
• Vanini G, Torterolo P, Baghdoyan HA, and Lydic R.  The shared circuits of sleep and anesthesia.  In:  The Neuroscientific Foundations of Anesthesiology, edited by GA Mashour and R Lydic, Oxford, pp 33-44, 2011.
• Brevig HN and Baghdoyan HA.  Neurotransmitters and neuromodulators regulating sleep and wakefulness.  In:  Encyclopedia of Behavioral Neuroscience, volume 3, edited by GF Koob, M Le Moal, and RF Thompson, Academic Press, Oxford, pp 456-463, 2010.