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Patrick Michael Fuller, Ph.D., M.S.
Vice Chair of Research
Director, Laboratory of Systems Neuroscience
Professor, Department of Neurological Surgery
Visiting Professor, University of Tsukuba, Japan
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Research/Academic Interests
Dr. Fuller's research focuses on brain substrates of behavioral state control, including the temporal organization of behavioral state imparted by the hypothalamic circadian clock. This work spans a discontinuous continuum from coma (irreversible absence of wakeful consciousness), to sleep (reversible absence of wakeful consciousness), to the fullest expression of wakeful consciousness (complete neurobehavioral and electroencephalographic (EEG) arousal). In undertaking this work, the Fuller lab has sought to identify and characterize the key circuits, nodes, cell populations and transmitters that are necessary for normal levels and manifestations of neurobehavioral and EEG phenomenon during wakefulness/cortical arousal, and sleep.
Damage to discrete subcortical cell populations can reduce conscious awareness or even produce coma after stroke or brain injury, and work in the Fuller lab seeks to promote recovery by manipulating these neurons, and/or their postsynaptic targets. In addition, a more detailed understanding of the brain substrates that initiate, organize and maintain sleep will not only provide a better understanding of how sleep contributes to normal brain function, but may also inform how disrupted sleep could be improved in a wide range of neurologic, neurodegenerative and neuropsychiatric conditions, e.g., Alzheimer's disease, TBI, PTSD. To address these challenges, the Fuller lab has employed and developed a wide range of methodologies, including morphological methods, genetic engineering techniques in mice and rats, brain slice electrophysiology, in vivo single cell and population Ca+2-based imaging and optetrode/LFP recordings, optogenetics, chemogenetics, single neuron and single nuclei transcriptomics, and cell-specific mapping techniques.
Thus far work in the Fuller lab has resulted in many papers describing heretofore unrecognized cell groups, transmitters and circuits that are necessary for normal levels of sleep and wakefulness. From a translational perspective findings from the Fuller lab have suggested new cellular targets for increasing forebrain activation in dementia and the minimally conscious state, as well as for treating sleep disorders, ranging from primary insomnia and hyperarousal of PTSD to idiopathic hypersomnia.
Division
Neurological Surgery
Undergraduate School
B.S., UC Davis, Davis CA 1997
Other School
M.S., Exercise Physiology, UC Davis, Davis CA 2002
Other School
Ph.D., Molecular and Cellular Physiology, UC Davis, Davis CA 2004
Fellowship
Neurology/Neuroscience, Harvard Medical School/Beth Israel Deaconess Medical Center, Boston MA 2005-2007
A. Clifford Barger Excellence in Mentoring Award, Harvard Medical School, 2019
Distinguished Service Award, Sleep Research Society, 2018
Standing Study Section Member, Neuroendocrinology, Neuroimmunology, Rhythms and Sleep, 2017
Full Preceptor, HMS, Division of Sleep Medicine, Research Training Program, 2016
Fellowship from Japan Society for the Promotion of Science (JSPS), 2015
De Luca R, Nardone S, Grace KP, Venner A, Cristofolini M, Bandaru SS, Sohn LT, Kong D, Mochizuki T, Viberti B, Zhu L, Zito A, Scammell TE, Saper CB, Lowell BB, Fuller PM, Arrigoni E. Orexin neurons inhibit sleep to promote arousal. Nat Commun. 2022 Jul 18;13(1):4163. doi:10.1038/s41467-022-31591-y. PMID:35851580.
Arrigoni E, Fuller PM. Addicted to dreaming. Science. 2022 Mar 4;375(6584):972-973. doi: 10.1126/science.abo1987. Epub 2022 Mar 3. PMID: 35239395.
Todd WD, Venner A, Anaclet C, Broadhurst RY, De Luca R, Bandaru SS, Issokson L, Hablitz LM, Cravetchi O, Arrigoni E, Campbell JN, Allen CN, Olson DP, Fuller PM. Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations. Nat Commun. 2020 Sep 2;11(1):4410. doi:10.1038/s41467-020-17197-2. PMID:32879310.
Venner A, De Luca R, Sohn LT, Bandaru SS, Verstegen AMJ, Arrigoni E, Fuller PM. An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep. Curr Biol. 2019 Dec 16;29(24):4155-4168.e5. doi:10.1016/j.cub.2019.10.026. Epub 2019 Nov 21. PMID:31761703.
Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, Finn MB, Manis M, Geerling JC, Fuller PM, Lucey BP, Holtzman DM. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019 Feb 22;363(6429):880-884. doi:10.1126/science.aav2546. Epub 2019 Jan 24. PMID:30679382.
Todd WD, Fenselau H, Wang JL, Zhang R, Machado NL, Venner A, Broadhurst RY, Kaur S, Lynagh T, Olson DP, Lowell BB, Fuller PM, Saper CB. A hypothalamic circuit for the circadian control of aggression. Nat Neurosci. 2018 May;21(5):717-724. doi:10.1038/s41593-018-0126-0. Epub 2018 Apr 9. PMID:29632359.
Pedersen NP, Ferrari L, Venner A, Wang JL, Abbott SBG, Vujovic N, Arrigoni E, Saper CB, Fuller PM. Supramammillary glutamate neurons are a key node of the arousal system. Nat Commun. 2017 Nov 10;8(1):1405. doi:10.1038/s41467-017-01004-6. PMID:29123082.
Kaur S, Wang JL, Ferrari L, Thankachan S, Kroeger D, Venner A, Lazarus M, Wellman A, Arrigoni E, Fuller PM, Saper CB. A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia. Neuron. 2017 Dec 6;96(5):1153-1167.e5. doi:10.1016/j.neuron.2017.10.009. Epub 2017 Nov 2. PMID:29103805.
Anaclet C, Pedersen NP, Ferrari LL, Venner A, Bass CE, Arrigoni E, Fuller PM. Basal forebrain control of wakefulness and cortical rhythms. Nat Commun. 2015 Nov 3;6:8744. doi:10.1038/ncomms9744. PMID:26524973.
Sherman D, Fuller PM, Marcus J, Yu J, Zhang P, Chamberlin NL, Saper CB, Lu J. Anatomical Location of the Mesencephalic Locomotor Region and Its Possible Role in Locomotion, Posture, Cataplexy, and Parkinsonism. Front Neurol. 2015 Jun 24;6:140. doi:10.3389/fneur.2015.00140. PMID:26157418.