Faculty Profile

Patrick M. Fuller, PhD

PMF profile photo 2016
Associate Professor of Neurology, Harvard Medical School
Associate Professor of Neurology, Department of Neurology, Beth Israel Deaconess Medical Center

Administrative Title(s)

Deputy Head
Research Division, Department of Neurology 

Other Affiliation(s)

Faculty Training Coordinator
Harvard Medical School, Division of Sleep Medicine

Professor (SIGMA), University of Tsukuba, Japan

See publications


Inter-office Mail Address

BIDMC, E/CLS 664

Email pfuller@bidmc.harvard.edu

Society Memberships

Society for Neuroscience
Sleep Research Society
American Physiological Society
Sigma Xi
International Society for Gravitational Physiology

Research Unit(s)

Division of Sleep Medicine
Systems Neurobiology Group (Fuller)

Research Interests

From an investigational standpoint, my laboratory focuses broadly on identifying and characterizing neuronal circuitry underlying behavioral state control, including key circuit nodes, their transmitters and their targets.  The over-arching goal of my lab is to elucidate the cellular and synaptic “neurocircuit basis” supporting sleep and cortical/behavioral arousal.  This work spans a significant continuum and includes lines of investigation involving sleep and circadian regulation to mechanisms of anesthesia to circuitry - in particular that of the basal forebrain - supporting neurobehavioral and electrocortical arousal (i.e., wakeful consciousness).

To clarify the central circuits supporting these processes, we employ a wide range of methodologies including: morphological methods, genetic engineering techniques in mice and rats, in vitro and in vivo electrophysiology, optogenetics, chemogenetics, in vivo cellular imaging, viral reagents and conditional mapping systems.  More specifically, we develop and use transgenic, knockout, knockin, and cre-dependent AAV viral approaches (for delivery of optogenetic, DREADD, neurotoxin and tracing reagents) to manipulate and map neuronal circuits.  The ultimate goal of our work is to link the in vivo activity of defined sets of neurons with neurobehavioral, electroencephalographic and physiological outcomes in behaving animals.

Trainees

Graduate students and fellows
Nina Vujovic, PhD candidate, 2007-2014
Elizabeth May, BS, 2009-2010
Kelly Doolin, BS, 2011
Christelle Anaclet, PhD, 2011-present
Anne Venner, PhD, 2011-present
Kobi Griffith, summer 2014
Rebecca Broadhurst, BS, 2017-
Kevin Grace, PhD, 2017-

Undergraduate research students
David Sherman
Mary Silvalayathong
Elizabeth May
John Lin
Tanya Bajwa
Elaine Chang
Ashley Swan
Sara Hyde
Kelly Doolin
Kobi Griffith
Shoshanna Freeman
Cameron Friedman
Amalie Kristiansen
Jorunn Hjaltadottir

Mentor(s)


Research Funding

NIH/NINDS R01, PI 2017-2022
Lateral hypothalamic arousal pathways

NIH/NINDS R01, PI 2011-2020
Basal forebrain and cortical arousal

NIH/NINDS R01, PI 2015-2020
Brainstem regulation of sleep

NIH/NINDS R01, Co-I 2015-2020
Basal forebrain-hypothalamic regulation of sleep-wake cycles
(PI: Arrigoni)

NIH/NINDS R01, Co-I 2014-2019
Supramammilary control of wake
(PI: Saper)

NHLBI, PPG on Sleep and Sleep Apnea, Leader Core B, 2015-2020
Mechanisms of cardiovascular and EEG arousal in OSA
(PI: Saper)

NARSAD, Mentor (PI, Venner), 2014-2016

NIH/NIMH K99/R00, Mentor (PI, Anaclet), 2014-2019


Teaching

"Circadian Biology: From Cellular Oscillators to Sleep Regulation", Biol. 186, Harvard College, lecturer on, "The Suprachiasmatic Nucleus: A Mammalian Circadian Clock."

Selected Publications

Anaclet C, De Luca R, Venner A, Malyshevskaya O, Lazarus M, Arrigoni E, Fuller PM.
Genetic activation, inactivation and deletion reveal a limited and nuanced
role for somatostatin-containing basal forebrain neurons in behavioral state
control. J Neurosci. 2018 May 7. pii: 2955-17 [PMID: 29735555]

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 [PMID: 29632359]

Hooper A, Fuller PM, Maguire J. Hippocampal corticotropin-releasing hormone neurons support recognition memory and modulate hippocampal excitability. PLoS One. 2018 Jan 18;13(1):e0191363 [PMID: 29346425]

Pedersen NP, Ferrari L, Venner A, Wang JL, Abbott SBG, Arrigoni E, Saper CB, Fuller PM.  Supramammillary glutamate neurons are a key node of the arousal system. Nature Communication. 2017 Nov 10;8(1):1405 [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

Guo CN, Yang WJ, Zhan SQ, Yang XF, Chen MC, Fuller PM, Lu J. Targeted
disruption of supraspinal motor circuitry reveals a distributed network
underlying Restless Legs Syndrome (RLS)-like movements in the rat. Sci Rep. 2017
Aug 29;7(1):9905. [PMID: 28852150]

Woodworth HL, Batchelor HM, Beekly BG, Bugescu R, Brown JA, Kurt G, Fuller PM,
Leinninger GM. Neurotensin Receptor-1 Identifies a Subset of Ventral Tegmental
Dopamine Neurons that Coordinates Energy Balance. Cell Rep. 2017 Aug
22;20(8):1881-1892. [PMID: 28834751]

Schallner N, Lieberum JL, Gallo D, LeBlanc RH 3rd, Fuller PM, Hanafy KA,
Otterbein LE. Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity
of Subarachnoid Hemorrhage in Mice. Stroke. 2017 Sep;48(9):2565-2573. [PMID: 28747460]

Anaclet C, Griffith K, Fuller PM. Activation of the GABAergic Parafacial Zone
Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants
Armodafinil and Caffeine. Neuropsychopharmacology. 2017 Jul 19. [PMID: 28722021]

Rukhadze I, Carballo NJ, Bandaru SS, Malhotra A, Fuller PM, Fenik VB.
Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these
muscles. Respir Physiol Neurobiol. 2017 Oct;244:41-50. [PMID: 28711601]

Chen MC, Vetrivelan R, Guo CN, Chang C, Fuller PM, Lu J. Ventral medullary
control of rapid eye movement sleep and atonia. Exp Neurol. 2017 Apr;290:53-62. [PMID: 28077261]

Kroeger D, Ferrari LL, Petit G, Mahoney CE, Fuller PM, Arrigoni E, Scammell
TE. Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine
Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice. J
Neurosci. 2017 Feb 1;37(5):1352-1366 [PMID: 28039375]

Qiu MH, Chen MC, Fuller PM, Lu J. Stimulation of the Pontine Parabrachial
Nucleus Promotes Wakefulness via Extra-thalamic Forebrain Circuit Nodes. Curr
Biol. 2016 Sep 12;26(17):2301-12. [PMID: 27546576]

Venner A, Anaclet C, Broadhurst RY, Saper CB, Fuller PM. A Novel Population of
Wake-Promoting GABAergic Neurons in the Ventral Lateral Hypothalamus. Curr Biol.
2016 Aug 22;26(16):2137-43. [PMID: 27426511]

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.[PMID: 26524973]

Gompf HS, Budygin EA, Fuller PM, Bass CE. Targeted genetic manipulations of
neuronal subtypes using promoter-specific combinatorial AAVs in wild-type
animals.
Front Behav Neurosci. 2015 Jul 2;9:152. [PMID: 26190981]

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. [PMID: 26157418]

Unger EK, Burke KJ Jr, Yang CF, Bender KJ, Fuller PM, Shah NM. Medial
amygdalar aromatase neurons regulate aggression in both sexes.
Cell Rep. 2015 Feb 3;10(4):453-62. [PMID: 25620703]

Chen MC, Ferrari L, Sacchet MD, Foland-Ross LC, Qiu MH, Gotlib IH, Fuller PM,
Arrigoni E, Lu J. Identification of a direct GABAergic pallidocortical pathway in
rodents.
Eur J Neurosci. 2015 Mar;41(6):748-59. [PMID: 25581560]

Gompf HS, Fuller PM, Hattar S, Saper CB, Lu J. Impaired circadian
photosensitivity in mice lacking glutamate transmission from retinal melanopsin
cells.
J Biol Rhythms. 2015 Feb;30(1):35-41. [PMID: 25512304]

Yazaki-Sugiyama Y, Yanagihara S, Fuller PM, Lazarus M. Acute inhibition of a
cortical motor area impairs vocal control in singing zebra finches.
Eur J Neurosci. 2015 Jan;41(1):97-108. [PMID: 25354166]

Shah BP, Vong L, Olson DP, Koda S, Krashes MJ, Ye C, Yang Z, Fuller PM, Elmquist JK, Lowell BB. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus.
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13193-8. [PMID: 25157144]

Anaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, Fuller PM. The GABAergic parafacial zone is a medullary slow wave sleep-promoting center.
Nat Neurosci. 2014 Sep;17(9):1217-24. [PMID: 25129078]

Vetrivelan R, Saper CB, Fuller PM. Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions.
Nat Sci Sleep. 2014 May 2;6:57-63. [PMID: 24833927]

Pei H, Sutton AK, Burnett KH, Fuller PM, Olson DP. AVP neurons in the paraventricular nucleus of the hypothalamus regulate feeding.
Mol Metab. 2014 Jan 8;3(2):209-15. [PMID: 24634830]

Oishi Y, Williams RH, Agostinelli L, Arrigoni E, Fuller PM, Mochizuki T, Saper CB, Scammell TE. Role of the medial prefrontal cortex in cataplexy.
J Neurosci. 2013 Jun 5;33(23):9743-51. [PMID:23739971]

Kaur S, Pedersen NP, Yokota S, Hur EE, Fuller PM, Lazarus M, Chamberlin NL, Saper CB. Glutamatergic signaling from the parabrachial nucleus plays a critical role in hypercapnic arousal.
J Neurosci. 2013 May 1;33(18):7627-40. [PMID: 23637157]

Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J. Identification and characterization of a sleep-active cell group in the rostral medullary brainstem.
J Neurosci. 2012 Dec 12;32(50):17970-6. [PMID: 23238713]

Vetrivelan R, Fuller PM, Yokota S, Lu J, Saper CB. Metabolic effects of chronic sleep restriction in rats.
Sleep. 2012 Nov 1;35(11):1511-20. [PMID: 23115400]

Kong D, Tong Q, Ye C, Koda S, Fuller PM, Krashes MJ, Vong L, Ray RS, Olson DP, Lowell BB. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell. 2012 Oct 26;151(3):645-57. [PMID: 23101631]

Thankachan S, Fuller PM, Lu J. Movement- and behavioral state-dependent activity of pontine reticulospinal neurons.
Neuroscience. 2012 Sep 27;221:125-39. [PMID: 22796072]

Krenzer M, Anaclet C, Vetrivelan R, Wang N, Vong L, Lowell BB, Fuller PM, Lu J. Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia.
PLoS One. 2011;6(10):e24998. Epub 2011 Oct 17. [PMID: 22043278]

Lazarus M, Saper CB, Fuller PM.  Genetic dissection of neural circuitry regulating behavioral state using conditional transgenics.  
Sleep and Biological Rhythms. 2011 9(1):78-83. [PMID: 21280045]

Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J. Reassessment of the structural basis of the ascending arousal system.
J Comp Neurol. 2011 Apr 1;519(5):933-56. [PMID: 21280045]

Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching.
Neuron. 2010 Dec 22;68(6):1023-42. [PMID: 21172606]

Gompf HS, Mathai C, Fuller PM, Wood DA, Pedersen NP, Saper CB, Lu J. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment.
J Neurosci. 2010 Oct 27;30(43):14543-51. [PMID: 20980612]

Qiu MH, Vetrivelan R, Fuller PM, Lu J. Basal ganglia control of sleep-wake behavior and cortical activation. 
Eur J Neurosci. 2010 Jan 25. [PMID: 20105243]

Anaclet C, Pedersen NP, Fuller PM, Lu J. Brainstem Circuitry Regulating Phasic Activation of Trigeminal Motoneurons during REM Sleep.
PLoS One. 2010 Jan 20;5(1):e8788 [PMID: 20098748]

Ingham ES, Günhan E, Fuller PM, Fuller CA. Immunotoxin-induced ablation of melanopsin retinal ganglion cells in a non-murine mammalian model.
J Comp Neurol. 2009 Sep 10;516(2):125-40. [PMID: 19575450]

Fuller PM, Lu J, Saper CB. Standards of evidence in chronobiology: A response.
J Circadian Rhythms. 2009 Jul 22;7:9. [PMID: 19624818]

Vetrivelan R, Fuller PM, Tong Q, Lu J. Medullary circuitry regulating rapid eye movement sleep and motor atonia.
J Neurosci. 2009 Jul 22;29(29):9361-9. [PMID: 19625526]

Greco MA, Fuller PM, Jhou TC, Martin-Schild S, Zadina JE, Hu Z, Shiromani P, Lu J. Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus.
Brain Res. 2008 Dec 15;1245:96-107. Epub 2008 Sep 24. PubMed PMID: 18840417; [Central PMCID: PMC2753822]

Pedersen NP, Fuller PM, Lu J, Saper CB. In the flicker of an eye.
J Physiol. 2008 Jul 15;586(14):3305-6. [PMID: 18625803]

Fuller PM, Lu J, Saper CB. Differential rescue of light- and food-entrainable circadian rhythms.
Science. 2008 May 23;320(5879):1074-7. [PMID: 18497298]

Fuller PM, Fuller CA. Genetic evidence for a neurovestibular influence on the mammalian circadian pacemaker.
J Biol Rhythms. 2006 Jun;21(3):177-84. PubMed [PMID: 16731657]

Fuller PM, Baldwin KM, Fuller CA. Parallel and divergent adaptations of rat soleus and plantaris to chronic exercise and hypergravity.
Am J Physiol Regul Integr Comp Physiol. 2006 Feb;290(2):R442-8. Epub 2005 Sep 22. [PMID: 16179485]

Fuller PM, Jones TA, Jones SM, Fuller CA. Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei.
Neuroscience. 2004;129(2):461-71. [PMID: 15501603]

Fuller PM, Jones TA, Jones SM, Fuller CA. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15723-8. Epub 2002 Nov 14. [PMID: 12434016]

Fuller PM, Warden CH, Barry SJ, Fuller CA. Effects of 2-G exposure on temperature regulation, circadian rhythms, and adiposity in UCP2/3 transgenic mice.
J Appl Physiol. 2000 Oct;89(4):1491-8. [PMID: 11007587]

Reviews

Peever J, Fuller PM. The Biology of REM Sleep. Curr Biol. 2017 Nov 20;27(22):R1237-R1248.

Saper CB, Fuller PM. Wake-sleep circuitry: an overview. Curr Opin Neurobiol.
2017 Jun;44:186-192. [PMID: 28577468]

Anaclet C, Fuller PM. Brainstem regulation of slow-wave-sleep. Curr Opin
Neurobiol. 2017 Jun;44:139-143. [PMID: 28500870]

Arrigoni E, Chen MC, Fuller PM. The anatomical, cellular and synaptic basis of
motor atonia during rapid eye movement sleep. J Physiol. 2016 Oct
1;594(19):5391-414. [PMID:
27060683]

Peever J, Fuller PM. Neuroscience: A Distributed Neural Network Controls REM
Sleep. Curr Biol. 2016 Jan 11;26(1):R34-5.
[PMID: 26766231]

Fuller PM, Yamanaka A, Lazarus (2015) How genetically-engineered systems are helping to define, and in some cases redefine, the neurobiological basis of sleep and wake.  Temperature.  2(3):406-417

Lazarus M, Saper CB, Fuller PM  (2011) Genetic dissection of neural circuitry regulating behavioral state using conditional transgenics. 
Sleep and Biological Rhythms. 9(1):78-83
 
Fuller PM, Yamanaka A, Lazarus (2015) How genetically-engineered systems are helping to define, and in some cases redefine, the neurobiological basis of sleep and wake.  Temperature.  2(3):406-417

Fuller PM, Saper CB, Lu J. The pontine REM switch: past and present.
J Physiol. 2007 Nov 1;584(Pt 3):735-41. Epub 2007 Sep 20. Review. [PMID: 17884926]

Saper CB, Fuller PM. Inducible clocks: living in an unpredictable world.
Cold Spring Harb Symp Quant Biol. 2007;72:543-50. Review. [PMID: 18419313]

Fuller PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback.
J Biol Rhythms. 2006 Dec;21(6):482-93. Review. [PMID: 17107938]

Books and Chapters

Fuller PM, Buxton OM, Zee P (2013) Neurobiology of Sleep: Mechanisms. 
Atlas of Clinical Sleep Medicine.  Meir Kryger, Editor-in-Chief

Arrigoni EA and Fuller PM. Overview of Sleep: Physiology and Neuroanatomy. 
In: Therapy in Sleep Medicine.  Eds. Barkoukis, Matheson, Ferber and Doghramji. 2012.

Fuller PM, Zee PC, Buxton OM. Chapter 3.1 Sleep Mechanisms. In Kryger MH (ed).
In: Atlas of Clinical Sleep Medicine. Elsevier. Philadelphia 2010; 20-25.

Fuller PM and Lu J, Editors.  Neurobiology of Sleep. 
In: SRS Basics of Sleep Guide, 2nd Edition, 2009.

Fuller PM and Lu J. Sleep and sleep states: hypothalamic regulation.
In: The Encyclopedia of Neuroscience. Editor-in-Chief:  Larry R. Squire, 2009.

Fuller PM and Lu J (2009). Dopamine control of arousal. 
In: The Encyclopedia of Neuroscience. Editor-in-Chief:  Larry R. Squire, 2009.

C Amlaner and PM Fuller, Editors. SRS Basics of Sleep Guide, 2nd Edition, 2009. 

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