Faculty Profile

Priyattam J. Shiromani, PhD


Associate Professor of Neurology, Harvard Medical School
Associate Neuroscientist, Department of Neurology, Brigham and Women's Hospital

See publications


Phone 857-203-6162

Society Memberships

Society for Neuroscience
Sleep Research Society
International Behavioral Neuroscience Society

Research Unit(s)

Molecular Sleep Laboratory
Department of Biomedical Research

Research Interests

Research in the laboratory investigates the mechanisms responsible for the decline in sleep with aging. Using state-of-the art gene chip technology we have probed changes in 8,800 genes in a region of the brain responsible for arousal. We find that with aging there is a breakdown in the expression of genes critical for neuronal activity. Current effort is to implement an intervention, such as exercise, to block the cell death cascade. We find that exercise can increase arousal, normalize sleep and increase the activity of key EEG frequencies associated with cognitive function. Most interestingly, these changes persist for several weeks after exercise has ended. This simple intervention provides hope that exercise, even when it is started for the first time late in life, can improve quality of life. We recommend that exercise be started during the teenage years, and continue throughout life as a means of combating obesity and improving sleep and cognition.

Trainees

Alva, Suraj, M.D (1999-2001); Radhika Basheer, PhD (1995-1998); Carlos Blanco-Centurion, PhD (2000 to present); Gerashchenko, Dmitry, Ph.D. (1999-2005); Greco, MaryAnn. Ph.D (1994-2001); Hallet, Laura (Undergraduate, Summer 2002, 2003); Liu, Meng, Ph.D (2006-Present); Jun Lu, PhD (1996-3/2004); Magner Meredith (1993-1996); Max, Ahn M.D (1999-2000); Morgan, Karen, M.D (1999-2001); Carlos Murillo-Rodriguez, PhD (May, 2001-June, 2004). Received Young Investigator Award (Honorable Mention), Sleep Research Society.
Salin-Pascal, Rafael M.D, Ph.D (1998-1999); Sang, Q, Ph.D (1999); Sherin John (1994-1997); Sullivan, Mary Rose, Ph.D (1999-2001); Upadhyay, Urvashi (Undergraduate, Summer of 1998 and 1999); Wagner, Dean (Undergraduate, 1996-1999); Whitehead, Sara, M.D (2001); Xu, Man M.D. (2002-2004)

Research Funding

Sponsor:Veterans Affairs Medical Research Service,
Title: Sleep Neurobiology and Circuitry,
PI: Shiromani, PJ, Ph.D

Sponsor: NIH/NINDS
Title: Brain Mechanisms of Narcolepsy
PI: Shiromani, PJ. Ph.D

Sponsor: NIH/NINDS
Title: Basal Forebrain Hypocretin Regulation of Wake
PI: Shiromani, PJ, Ph.D

Sponsor: NIH/NIMH
Title: Hypothalamic Regulation of Sleep
PI: Shiromani, PJ, Ph.D

Selected Publications

Salin-Pascual RJ, Valencia-Flores M, Campos RM, Castano A, Shiromani PJ. Caffeine challenge in insomniac patients after total sleep deprivation.
Sleep Med. 2006 Mar;7(2):141-5. Epub 2006 Feb 3. [PMID: 16459138]

Blanco-Centurion CA, Shiromani PJ. Beneficial effects of regular exercise on sleep in old F344 rats.
Neurobiol Aging. 2005 Nov 21; [Epub ahead of print] [PMID: 16309796] 

Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ. Insomnia following hypocretin2-saporin lesions of the substantia nigra.
Neuroscience. 2006;137(1):29-36. Epub 2005 Nov 11. [PMID: 16289583] 

Arias-Carrion O, Murillo-Rodriguez E, Xu M, Blanco-Centurion C, Drucker-Colin R, Shiromani PJ. Transplantation of hypocretin neurons into the pontine reticular formation: preliminary results.
Sleep. 2004 Dec 15;27(8):1465-70. [PMID: 15683135] 

Gerashchenko D, Chou TC, Blanco-Centurion CA, Saper CB, Shiromani PJ. Effects of lesions of the histaminergic tuberomammillary nucleus on spontaneous sleep in rats.
Sleep. 2004 Nov 1;27(7):1275-81. [PMID: 15586780] 

Desarnaud F, Murillo-Rodriguez E, Lin L, Xu M, Gerashchenko D, Shiromani SN, Nishino S, Mignot E, Shiromani PJ. The diurnal rhythm of hypocretin in young and old F344 rats.
Sleep. 2004 Aug 1;27(5):851-6. [PMID: 15453542] 

Gerashchenko D, Shiromani PJ. Effects of inflammation produced by chronic lipopolysaccharide administration on the survival of hypocretin neurons and sleep.
Brain Res. 2004 Sep 3;1019(1-2):162-9. [PMID: 15306250] 

Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ. Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone.
Eur J Neurosci. 2004 May;19(10):2741-52. [PMID: 15147308]

Gerashchenko D, Shiromani PJ. Different neuronal phenotypes in the lateral hypothalamus and their role in sleep and wakefulness.
Mol Neurobiol. 2004 Feb;29(1):41-59. Review. [PMID: 15034222] 

Shiromani PJ, Xu M, Winston EM, Shiromani SN, Gerashchenko D, Weaver DR. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes.
Am J Physiol Regul Integr Comp Physiol. 2004 Jul;287(1):R47-57. Epub 2004 Mar 18. [PMID: 15031135] 

Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S, Mignot E, Shiromani PJ. Relationship between CSF hypocretin levels and hypocretin neuronal loss.
Exp Neurol. 2003 Dec;184(2):1010-6. [PMID: 14769395]

Murillo-Rodriguez E, Blanco-Centurion C, Sanchez C, Piomelli D, Shiromani PJ. Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.
Sleep. 2003 Dec 15;26(8):943-7. [PMID: 14746372]

Murillo-Rodriguez E, Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ. The diurnal rhythm of adenosine levels in the basal forebrain of young and old rats.
Neuroscience. 2004;123(2):361-70. [PMID: 14698744]

Goulet M, Shiromani PJ, Ware CM, Strong RA, Boismenu R, Rusche JR. A secretin i.v. infusion activates gene expression in the central amygdala of rats.
Neuroscience. 2003;118(4):881-8. [PMID: 12732234]

Gerashchenko D, Blanco-Centurion C, Greco MA, Shiromani PJ. Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats.
Neuroscience. 2003;116(1):223-35. [PMID: 12535955]

Salin-Pascual RJ, Upadhyay U, Shiromani PJ. Effects of hypocaloric diet on sleep in young and old rats.
Neurobiol Aging. 2002 Sep-Oct;23(5):771-6. [PMID: 12392780]

Lu J, Bjorkum AA, Xu M, Gaus SE, Shiromani PJ, Saper CB. Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep.
J Neurosci. 2002 Jun 1;22(11):4568-76. [PMID: 12040064]

Salin-Pascual R, Gerashchenko D, Greco M, Blanco-Centurion C, Shiromani PJ. Hypothalamic regulation of sleep.
Neuropsychopharmacology. 2001 Nov;25(5 Suppl):S21-7. Review. [PMID: 11682269] 

Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat.
J Neurosci. 2001 Sep 15;21(18):7273-83. [PMID: 11549737]

Gerashchenko D, Salin-Pascual R, Shiromani PJ. Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta.
Brain Res. 2001 Sep 14;913(1):106-15. [PMID: 11532254]

Lu J, Zhang YH, Chou TC, Gaus SE, Elmquist JK, Shiromani P, Saper CB. Contrasting effects of ibotenate lesions of the paraventricular nucleus and subparaventricular zone on sleep-wake cycle and temperature regulation.
J Neurosci. 2001 Jul 1;21(13):4864-74. [PMID: 11425913] 

Wagner D, Salin-Pascual R, Greco MA, Shiromani PJ. Distribution of hypocretin-containing neurons in the lateral hypothalamus and C-fos-immunoreactive neurons in the VLPO.
Sleep Res Online. 2000;3(1):35-42. [PMID: 11382898]

Basheer R, Shiromani PJ. Effects of prolonged wakefulness on c-fos and AP1 activity in young and old rats.
Brain Res Mol Brain Res. 2001 Apr 18;89(1-2):153-7. [PMID: 11311986]

Greco MA, Shiromani PJ. Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats.
Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):176-82. [PMID: 11295245] 

Shiromani PJ, Basheer R, Thakkar J, Wagner D, Greco MA, Charness ME. Sleep and wakefulness in c-fos and fos B gene knockout mice.
Brain Res Mol Brain Res. 2000 Aug 14;80(1):75-87. [PMID: 11039731] 

Lu J, Greco MA, Shiromani P, Saper CB. Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep.
J Neurosci. 2000 May 15;20(10):3830-42. [PMID: 10804223] 

Greco MA, Lu J, Wagner D, Shiromani PJ. c-Fos expression in the cholinergic basal forebrain after enforced wakefulness and recovery sleep.
Neuroreport. 2000 Feb 28;11(3):437-40. [PMID: 10718290] 

Shiromani PJ, Lu J, Wagner D, Thakkar J, Greco MA, Basheer R, Thakkar M. Compensatory sleep response to 12 h wakefulness in young and old rats.
Am J Physiol Regul Integr Comp Physiol. 2000 Jan;278(1):R125-33. [PMID: 10644630] 

Greco MA, McCarley RW, Shiromani PJ. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.
Neuroscience. 1999;93(4):1369-74. [PMID: 10501461] 

Lu J, Shiromani P, Saper CB. Retinal input to the sleep-active ventrolateral preoptic nucleus in the rat.
Neuroscience. 1999;93(1):209-14. [PMID: 10430484]

Basheer R, Magner M, McCarley RW, Shiromani PJ. REM sleep deprivation increases the levels of tyrosine hydroxylase and norepinephrine transporter mRNA in the locus coeruleus.
Brain Res Mol Brain Res. 1998 Jun 15;57(2):235-40. [PMID: 9675421]

Greco MA, Magner M, Overstreet D, Shiromani PJ. Expression of cholinergic markers in the pons of Flinders rats.
Brain Res Mol Brain Res. 1998 Apr;55(2):232-6. [PMID: 9582425] 

Basheer R, Sherin JE, Saper CB, Morgan JI, McCarley RW, Shiromani PJ. Effects of sleep on wake-induced c-fos expression.
J Neurosci. 1997 Dec 15;17(24):9746-50. [PMID: 9391027]

Shiromani PJ, Winston S, McCarley RW. Pontine cholinergic neurons show Fos-like immunoreactivity associated with cholinergically induced REM sleep.
Brain Res Mol Brain Res. 1996 May;38(1):77-84. [PMID: 8737670] 

Sherin JE, Shiromani PJ, McCarley RW, Saper CB. Activation of ventrolateral preoptic neurons during sleep.
Science. 1996 Jan 12;271(5246):216-9. [PMID: 8539624]

Shiromani PJ, Malik M, Winston S, McCarley RW. Time course of Fos-like immunoreactivity associated with cholinergically induced REM sleep.
J Neurosci. 1995 May;15(5 Pt 1):3500-8. [PMID: 7751925]

Shiromani PJ, Magner M, Winston S, Charness ME. Time course of phosphorylated CREB and Fos-like immunoreactivity in the hypothalamic supraoptic nucleus after salt loading.
Brain Res Mol Brain Res. 1995 Mar;29(1):163-71. [PMID: 7769993]

Shiromani PJ, Schwartz WJ. Towards a molecular biology of the circadian clock and sleep of mammals.
Adv Neuroimmunol. 1995;5(2):217-30. Review. [PMID: 7496615]

Shiromani PJ, Overstreet D. Free-running period of circadian rhythms is shorter in rats with a genetically upregulated central cholinergic system.
Biol Psychiatry. 1994 Nov 1;36(9):622-6. [PMID: 7833429]

Zoltoski RK, Velazquez-Moctezuma J, Shiromani PJ, Gillin JC. The relative effects of selective M1 muscarinic antagonists on rapid eye movement sleep.
Brain Res. 1993 Apr 16;608(2):186-90. [PMID: 8495352]

Gillin JC, Salin-Pascual R, Velazquez-Moctezuma J, Shiromani P, Zoltoski R. Cholinergic receptor subtypes and REM sleep in animals and normal controls.
Prog Brain Res. 1993;98:379-87. Review. [PMID: 8248526]

Giovannelli L, Shiromani PJ, Jirikowski GF, Bloom FE. Expression of c-fos protein by immunohistochemically identified oxytocin neurons in the rat hypothalamus upon osmotic stimulation.
Brain Res. 1992 Aug 14;588(1):41-8. [PMID: 1393570]

Shiromani PJ, Kilduff TS, Bloom FE, McCarley RW. Cholinergically induced REM sleep triggers Fos-like immunoreactivity in dorsolateral pontine regions associated with REM sleep.
Brain Res. 1992 May 15;580(1-2):351-7. [PMID: 1504815]

Shiromani PJ. Cholinergic mechanisms in sleep and circadian rhythms.
Clin Neuropharmacol. 1992;15 Suppl 1 Pt A:292A-293A. No abstract available. [PMID: 1498846]

Gillin JC, Sutton L, Ruiz C, Golshan S, Hirsch S, Warmann C, Shiromani P. Dose dependent inhibition of REM sleep in normal volunteers by biperiden, a muscarinic antagonist.
Biol Psychiatry. 1991 Jul 15;30(2):151-6. [PMID: 1912107] 

Siegel JM, Nienhuis R, Fahringer HM, Paul R, Shiromani P, Dement WC, Mignot E, Chiu C. Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla.
Science. 1991 May 31;252(5010):1315-8. [PMID: 1925546]

Shiromani PJ, Klemfuss H, Lucero S, Overstreet DH. Diurnal rhythm of core body temperature is phase advanced in a rodent model of depression.
Biol Psychiatry. 1991 May 1;29(9):923-30. [PMID: 2049491] 

Shiromani PJ, Velazquez-Moctezuma J, Overstreet D, Shalauta M, Lucero S, Floyd C. Effects of sleep deprivation on sleepiness and increased REM sleep in rats selectively bred for cholinergic hyperactivity.
Sleep. 1991 Apr;14(2):116-20. [PMID: 1650958] 

Velazquez-Moctezuma J, Shalauta M, Gillin JC, Shiromani PJ. Cholinergic antagonists and REM sleep generation.
Brain Res. 1991 Mar 8;543(1):175-9. [PMID: 2054672]

Shiromani PJ, Floyd C, Velazquez-Moctezuma J. Pontine cholinergic neurons simultaneously innervate two thalamic targets.
Brain Res. 1990 Nov 5;532(1-2):317-22. [PMID: 2282524] 

Giovannelli L, Shiromani PJ, Jirikowski GF, Bloom FE. Oxytocin neurons in the rat hypothalamus exhibit c-fos immunoreactivity upon osmotic stress.
Brain Res. 1990 Oct 29;531(1-2):299-303. [PMID: 2126973] 

Velazquez-Moctezuma J, Shalauta MD, Gillin JC, Shiromani PJ. Microinjections of nicotine in the medial pontine reticular formation elicits REM sleep.
Neurosci Lett. 1990 Jul 31;115(2-3):265-8. [PMID: 2234504] 

Shiromani PJ, Lai YY, Siegel JM. Descending projections from the dorsolateral pontine tegmentum to the paramedian reticular nucleus of the caudal medulla in the cat.
Brain Res. 1990 May 28;517(1-2):224-8. Erratum in: Brain Res 1990 Sep 24;528(1):179. [PMID: 1695862]

Velazquez-Moctezuma J, Shalauta MD, Gillin JC, Shiromani PJ. Differential effects of cholinergic antagonists on REM sleep components.
Psychopharmacol Bull. 1990;26(3):349-53. [PMID: 2274635] 

Velazquez-Moctezuma J, Shiromani PJ, Gillin JC. Acetylcholine and acetylcholine receptor subtypes in REM sleep generation.
Prog Brain Res. 1990;84:407-13. Review. No abstract available. [PMID: 2267312]

Velazquez-Moctezuma J, Gillin JC, Shiromani PJ. Effect of specific M1, M2 muscarinic receptor agonists on REM sleep generation.
Brain Res. 1989 Nov 27;503(1):128-31. [PMID: 2482113]

Shiromani PJ, Armstrong DM, Gillin JC. Cholinergic neurons from the dorsolateral pons project to the medial pons: a WGA-HRP and choline acetyltransferase immunohistochemical study.
Neurosci Lett. 1988 Dec 19;95(1-3):19-23. [PMID: 2465510] 

Shiromani PJ, Overstreet D, Levy D, Goodrich CA, Campbell SS, Gillin JC. Increased REM sleep in rats selectively bred for cholinergic hyperactivity.
Neuropsychopharmacology. 1988 May;1(2):127-33. [PMID: 3251494] 

Shiromani PJ, Armstrong DM, Berkowitz A, Jeste DV, Gillin JC. Distribution of choline acetyltransferase immunoreactive somata in the feline brainstem: implications for REM sleep generation.
Sleep. 1988 Feb;11(1):1-16. [PMID: 2896380]

Shiromani PJ, Armstrong DM, Bruce G, Hersh LB, Groves PM, Gillin JC. Relation of pontine choline acetyltransferase immunoreactive neurons with cells which increase discharge during REM sleep.
Brain Res Bull. 1987 Mar;18(3):447-55. [PMID: 3580914] 

Shiromani PJ, Gillin JC, Henriksen SJ. Acetylcholine and the regulation of REM sleep: basic mechanisms and clinical implications for affective illness and narcolepsy.
Annu Rev Pharmacol Toxicol. 1987;27:137-56. No abstract available. [PMID: 3579239]

Sutin EL, Shiromani PJ, Kelsoe JR Jr, Storch FI, Gillin JC. Rapid-eye movement sleep and muscarinic receptor binding in rats are augmented during withdrawal from chronic scopolamine treatment.
Life Sci. 1986 Dec 22;39(25):2419-27. [PMID: 3796202]

Shiromani PJ, Fishbein W. Continuous pontine cholinergic microinfusion via mini-pump induces sustained alterations in rapid eye movement (REM) sleep.
Pharmacol Biochem Behav. 1986 Dec;25(6):1253-61. [PMID: 3809228]

Shiromani PJ, McGinty DJ. Pontine neuronal response to local cholinergic infusion: relation to REM sleep.
Brain Res. 1986 Oct 29;386(1-2):20-31. [PMID: 3779410]

Overstreet DH, Janowsky DS, Gillin JC, Shiromani PJ, Sutin EL. Stress-induced immobility in rats with cholinergic supersensitivity.
Biol Psychiatry. 1986 Jun;21(7):657-64. [PMID: 3708037]

Shiromani PJ, Siegel JM, Tomaszewski KS, McGinty DJ. Alterations in blood pressure and REM sleep after pontine carbachol microinfusion.
Exp Neurol. 1986 Feb;91(2):285-92. [PMID: 3943576]

Gutwein BM, Shiromani PJ, Fishbein W. Paradoxical sleep and memory: long-term disruptive effects of Anisomycin.
Pharmacol Biochem Behav. 1980 Mar;12(3):377-84. No abstract available. [PMID: 7393935]

Shiromani P, Gutwein BM, Fishbein W. Development of learning and memory in mice after brief paradoxical sleep deprivation.
Physiol Behav. 1979 May;22(5):971-8. No abstract available. [PMID: 228327]

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