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    William J Schwartz MD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-334-2527
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

        Overview 
        Narrative

        Biography

        William J. Schwartz received his M.D. (1974) and neurology residency training (1978-1981) at the University of California, San Francisco, completed a research fellowship at the National Institute of Mental Health (1975-1978), and was on the faculties of Harvard Medical School and the Massachusetts General Hospital (1981-1986) before moving to the University of Massachusetts. Visiting Professorships have included the Boerhaave Professor at Leiden University Medical Centre (2005) and the Baerends Visiting Chair at Rijksuniversiteit Groningen (2008), both in the Netherlands; and the Hood Fellow at the University of Auckland (2012), in New Zealand.

        Dr. William Schwartz, M.D.

        On the Neurobiology of Circadian Timekeeping

        Daily rhythms of physiology and behavior are governed by an endogenous timekeeping mechanism (a circadian "clock"), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day-night cycle. Our knowledge of circadian timekeeping of animals at the molecular and cellular levels is remarkable, and laboratories here in the Department of Neurobiology are playing major roles in these advances (Emery, Reppert, Weaver). This laboratory is focused at the tissue, organismal, and even supra-organismal levels of analysis, and how all levels of biological organization contribute to the emergent properties and increased complexity of the circadian system as a whole.

        Much of our work has focused on the suprachiasmatic nucleus (SCN) of the hypothalamus, the "master" circadian pacemaker of mammals, a tissue composed of multiple autonomous single-cell circadian oscillators (Figs 1 - 3). Our interests have included functional localization and energy metabolism, light-induced and endogenous gene expression, and the underyling dual oscillatory structure of the circadian pacemaker. We have been using molecular tools to show that some well-known circadian behaviors (e.g., "splitting," "forced desynchronization," and perhaps photoperiodism) emerge at the tissue level, in the dynamic interactions between SCN neurons rather than in the expression of "clock genes" within neurons.

        For the most part, experiments on circadian rhythmicity (including our own) have been carried out using singly-housed animals in plastic cages with temperature, humidity, and access to food rigidly controlled. Of course, many species ordinarily would not live out their lives in such seclusion. They form real ecological communities, and some live in colonies with highly developed social structures and a clear division of labor, requiring modifications to daily rhythms. For other animals living in the wild, social factors might act to synchronize their behaviors to achieve common goals or, alternatively, actively avoid each other to lessen competition for limited resources. We have been asking if the circadian system is involved in the inter-individual temporal adaptations of cohabiting animals and what mechanisms might be responsible (e.g., whether social interactions alter the rhythmicity of animals with genetically-defective clocks, and the identification of the neurobiological substrates (molecules, cells, and pathways) that underlie circadian adaptation to complex habitats).

        Figure 1. Coronal Nissl-stained section through the rat forebrain, including the bilaterally paired SCN (arrow).

        Figure 1. Coronal Nissl-stained section through the rat forebrain, including the bilaterally paired SCN (arrow).

        . Immunohistochemical arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) protein expression in a coronal section of the rat SCN, processed for double-label immunofluorescence and viewed using excitation wavelengths of 488 nm (green, for AVP) and 568 nm (red, for VIP).

        Figure 2. Immunohistochemical arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) protein expression in a coronal section of the rat SCN, processed for double-label immunofluorescence and viewed using excitation wavelengths of 488 nm (green, for AVP) and 568 nm (red, for VIP).

        Figure 3. The SCN exhibits endogenous day-night rhythms in energy metabolism, gene expression, and electrophysiological activity.

        Figure 3. The SCN exhibits endogenous day-night rhythms in energy metabolism, gene expression, and electrophysiological activity.



        Rotation Projects

        Rotations

        Rotation projects are available for students using a range of experimental approaches, including small animal stereotaxic neurosurgical procedures, longitudinal behavioral analyses, histochemical and autoradiographic imaging of neural patterns of protein and gene expression, and confocal microscopy. Contact the lab regarding specific interests and projects.



        Bibliographic 
        selected publications
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        1. Schwartz WJ. Thirty Years. J Biol Rhythms. 2016 Feb; 31(1):3.
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        2. Paul MJ, Indic P, Schwartz WJ. Social synchronization of circadian rhythmicity in female mice depends on the number of cohabiting animals. Biol Lett. 2015 Jun; 11(6):20150204.
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        3. Schwartz WJ. Body clocks. J Biol Rhythms. 2015 Feb; 30(1):3-4.
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        4. Leise TL, Indic P, Paul MJ, Schwartz WJ. Wavelet meets actogram. J Biol Rhythms. 2013 Feb; 28(1):62-8.
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        5. Gu C, Liu Z, Schwartz WJ, Indic P. Photic desynchronization of two subgroups of circadian oscillators in a network model of the suprachiasmatic nucleus with dispersed coupling strengths. PLoS One. 2012; 7(5):e36900.
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        6. Schwartz WJ, Tavakoli-Nezhad M, Lambert CM, Weaver DR, de la Iglesia HO. Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays. Proc Natl Acad Sci U S A. 2011 Oct 11; 108(41):17219-24.
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        7. Paul MJ, Schwartz WJ. Circadian rhythms: how does a reindeer tell time? Curr Biol. 2010 Mar 23; 20(6):R280-2.
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        8. Haddady S, Low HP, Billings-Gagliardi S, Riskind PN, Schwartz WJ. Pregnancy modulates precursor cell proliferation in a murine model of focal demyelination. Neuroscience. 2010 May 19; 167(3):656-64.
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        9. Schwartz WJ. Circadian rhythms: a tale of two nuclei. Curr Biol. 2009 Jun 9; 19(11):R460-2.
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        10. Paul MJ, Galang J, Schwartz WJ, Prendergast BJ. Intermediate-duration day lengths unmask reproductive responses to nonphotic environmental cues. Am J Physiol Regul Integr Comp Physiol. 2009 May; 296(5):R1613-9.
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        11. Low HP, Gréco B, Tanahashi Y, Gallant J, Jones SN, Billings-Gagliardi S, Recht LD, Schwartz WJ. Embryonic stem cell rescue of tremor and ataxia in myelin-deficient shiverer mice. J Neurol Sci. 2009 Jan 15; 276(1-2):133-7.
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        12. Mitome M, Low HP, Lora Rodriguez KM, Kitamoto M, Kitamura T, Schwartz WJ. Neuronal differentiation of EGF-propagated neurosphere cells after engraftment to the nucleus of the solitary tract. Neurosci Lett. 2008 Oct 31; 444(3):250-3.
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        13. Indic P, Schwartz WJ, Paydarfar D. Design principles for phase-splitting behaviour of coupled cellular oscillators: clues from hamsters with 'split' circadian rhythms. J R Soc Interface. 2008 Aug 6; 5(25):873-83.
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        14. Paul MJ, Zucker I, Schwartz WJ. Tracking the seasons: the internal calendars of vertebrates. Philos Trans R Soc Lond B Biol Sci. 2008 Jan 27; 363(1490):341-61.
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        15. Indic P, Schwartz WJ, Herzog ED, Foley NC, Antle MC. Modeling the behavior of coupled cellular circadian oscillators in the suprachiasmatic nucleus. J Biol Rhythms. 2007 Jun; 22(3):211-9.
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        16. Paul MJ, Schwartz WJ. On the chronobiology of cohabitation. Cold Spring Harb Symp Quant Biol. 2007; 72:615-21.
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        17. de la Iglesia HO, Schwartz WJ. Minireview: timely ovulation: circadian regulation of the female hypothalamo-pituitary-gonadal axis. Endocrinology. 2006 Mar; 147(3):1148-53.
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        18. Tavakoli-Nezhad M, Schwartz WJ. c-Fos expression in the brains of behaviorally "split" hamsters in constant light: calling attention to a dorsolateral region of the suprachiasmatic nucleus and the medial division of the lateral habenula. J Biol Rhythms. 2005 Oct; 20(5):419-29.
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        19. Silver R, Schwartz WJ. The suprachiasmatic nucleus is a functionally heterogeneous timekeeping organ. Methods Enzymol. 2005; 393:451-65.
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        20. Schwartz WJ. Sunrise and sunset in fly brains. Nature. 2004 Oct 14; 431(7010):751-2.
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        21. de la Iglesia HO, Meyer J, Schwartz WJ. Using Per gene expression to search for photoperiodic oscillators in the hamster suprachiasmatic nucleus. Brain Res Mol Brain Res. 2004 Aug 23; 127(1-2):121-7.
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        22. de la Iglesia HO, Cambras T, Schwartz WJ, Díez-Noguera A. Forced desynchronization of dual circadian oscillators within the rat suprachiasmatic nucleus. Curr Biol. 2004 May 4; 14(9):796-800.
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        23. de la Iglesia HO, Meyer J, Schwartz WJ. Lateralization of circadian pacemaker output: Activation of left- and right-sided luteinizing hormone-releasing hormone neurons involves a neural rather than a humoral pathway. J Neurosci. 2003 Aug 13; 23(19):7412-4.
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        24. Van Gelder RN, Herzog ED, Schwartz WJ, Taghert PH. Circadian rhythms: in the loop at last. Science. 2003 Jun 6; 300(5625):1534-5.
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        25. Meijer JH, Schwartz WJ. In search of the pathways for light-induced pacemaker resetting in the suprachiasmatic nucleus. J Biol Rhythms. 2003 Jun; 18(3):235-49.
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        26. De la Iglesia HO, Schwartz WJ. A subpopulation of efferent neurons in the mouse suprachiasmatic nucleus is also light responsive. Neuroreport. 2002 May 7; 13(6):857-60.
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        27. Zlomanczuk P, Mrugala M, de la Iglesia HO, Ourednik V, Quesenberry PJ, Snyder EY, Schwartz WJ. Transplanted clonal neural stem-like cells respond to remote photic stimulation following incorporation within the suprachiasmatic nucleus. Exp Neurol. 2002 Apr; 174(2):162-8.
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        28. Herzog ED, Schwartz WJ. A neural clockwork for encoding circadian time. J Appl Physiol (1985). 2002 Jan; 92(1):401-8.
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        29. Mitome M, Low HP, van den Pol A, Nunnari JJ, Wolf MK, Billings-Gagliardi S, Schwartz WJ. Towards the reconstruction of central nervous system white matter using neural precursor cells. Brain. 2001 Nov; 124(Pt 11):2147-61.
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        30. Schwartz WJ, de la Iglesia HO, Zlomanczuk P, Illnerová H. Encoding le quattro stagioni within the mammalian brain: photoperiodic orchestration through the suprachiasmatic nucleus. J Biol Rhythms. 2001 Aug; 16(4):302-11.
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        31. Paydarfar D, Schwartz WJ. An algorithm for discovery. Science. 2001 Apr 6; 292(5514):13.
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        32. Low HP, Savarese TM, Schwartz WJ. Neural precursor cells form rudimentary tissue-like structures in a rotating-wall vessel bioreactor. In Vitro Cell Dev Biol Anim. 2001 Mar; 37(3):141-7.
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        33. de la Iglesia HO, Meyer J, Carpino A, Schwartz WJ. Antiphase oscillation of the left and right suprachiasmatic nuclei. Science. 2000 Oct 27; 290(5492):799-801.
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        34. Mrugala M, Zlomanczuk P, Jagota A, Schwartz WJ. Rhythmic multiunit neural activity in slices of hamster suprachiasmatic nucleus reflect prior photoperiod. Am J Physiol Regul Integr Comp Physiol. 2000 Apr; 278(4):R987-94.
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        35. Jagota A, de la Iglesia HO, Schwartz WJ. Morning and evening circadian oscillations in the suprachiasmatic nucleus in vitro. Nat Neurosci. 2000 Apr; 3(4):372-6.
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        36. Bennett MR, Schwartz WJ. Altered circadian rhythmicity is an early sign of murine dietary thiamine deficiency. J Neurol Sci. 1999 Feb 1; 163(1):6-10.
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        37. Delville Y, De Vries GJ, Schwartz WJ, Ferris CF. Flank-marking behavior and the neural distribution of vasopressin innervation in golden hamsters with suprachiasmatic lesions. Behav Neurosci. 1998 Dec; 112(6):1486-501.
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        38. Castel M, Belenky M, Cohen S, Wagner S, Schwartz WJ. Light-induced c-Fos expression in the mouse suprachiasmatic nucleus: immunoelectron microscopy reveals co-localization in multiple cell types. Eur J Neurosci. 1997 Sep; 9(9):1950-60.
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        39. Schwartz WJ. Molecular time machines. The first gene involved in mammalian circadian timekeeping has been identified. Nat Med. 1997 Jul; 3(7):718-9.
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        40. Schwartz WJ. Understanding circadian clocks: from c-fos to fly balls. Ann Neurol. 1997 Mar; 41(3):289-97.
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        41. Bennett MR, Aronin N, Schwartz WJ. In vitro stimulation of c-Fos protein expression in the suprachiasmatic nucleus of hypothalamic slices. Brain Res Mol Brain Res. 1996 Nov; 42(1):140-4.
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        42. Miller JD, Morin LP, Schwartz WJ, Moore RY. New insights into the mammalian circadian clock. Sleep. 1996 Oct; 19(8):641-67.
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        43. Peters RV, Aronin N, Schwartz WJ. c-Fos expression in the rat intergeniculate leaflet: photic regulation, co-localization with Fos-B, and cellular identification. Brain Res. 1996 Jul 29; 728(2):231-41.
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        44. Schwartz WJ, Peters RV, Aronin N, Bennett MR. Unexpected c-fos gene expression in the suprachiasmatic nucleus of mice entrained to a skeleton photoperiod. J Biol Rhythms. 1996 Mar; 11(1):35-44.
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        45. Sumová A, Trávnícková Z, Peters R, Schwartz WJ, Illnerová H. The rat suprachiasmatic nucleus is a clock for all seasons. Proc Natl Acad Sci U S A. 1995 Aug 15; 92(17):7754-8.
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        46. Shiromani PJ, Schwartz WJ. Towards a molecular biology of the circadian clock and sleep of mammals. Adv Neuroimmunol. 1995; 5(2):217-30.
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        47. Bennett MR, Schwartz WJ. Are glia among the cells that express immunoreactive c-Fos in the suprachiasmatic nucleus? Neuroreport. 1994 Sep 8; 5(14):1737-40.
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        48. Schwartz WJ, Takeuchi J, Shannon W, Davis EM, Aronin N. Temporal regulation of light-induced Fos and Fos-like protein expression in the ventrolateral subdivision of the rat suprachiasmatic nucleus. Neuroscience. 1994 Feb; 58(3):573-83.
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        49. Takeuchi J, Shannon W, Aronin N, Schwartz WJ. Compositional changes of AP-1 DNA-binding proteins are regulated by light in a mammalian circadian clock. Neuron. 1993 Nov; 11(5):825-36.
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        50. Schwartz WJ. A clinician's primer on the circadian clock: its localization, function, and resetting. Adv Intern Med. 1993; 38:81-106.
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        51. Keilson GR, Schwartz WJ, Recht LD. The preponderance of posterior circulatory events is independent of the route of cardiac catheterization. Stroke. 1992 Sep; 23(9):1358-9.
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        52. Schwartz WJ, Zimmerman P. Lesions of the suprachiasmatic nucleus disrupt circadian locomotor rhythms in the mouse. Physiol Behav. 1991 Jun; 49(6):1283-7.
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        53. Schwartz WJ. Further evaluation of the tetrodotoxin-resistant circadian pacemaker in the suprachiasmatic nuclei. J Biol Rhythms. 1991; 6(2):149-58.
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        54. Schwartz WJ, Zimmerman P. Circadian timekeeping in BALB/c and C57BL/6 inbred mouse strains. J Neurosci. 1990 Nov; 10(11):3685-94.
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        55. Schwartz WJ. Different in vivo metabolic activities of suprachiasmatic nuclei of Turkish and golden hamsters. Am J Physiol. 1990 Nov; 259(5 Pt 2):R1083-5.
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        56. Aronin N, Sagar SM, Sharp FR, Schwartz WJ. Light regulates expression of a Fos-related protein in rat suprachiasmatic nuclei. Proc Natl Acad Sci U S A. 1990 Aug; 87(15):5959-62.
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        57. Felice KJ, Keilson GR, Schwartz WJ. 'Rubral' gait ataxia. Neurology. 1990 Jun; 40(6):1004-5.
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        58. Scammell TE, Schwartz WJ, Smith CB. No evidence for a circadian rhythm of protein synthesis in the rat suprachiasmatic nuclei. Brain Res. 1989 Aug 7; 494(1):155-8.
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        59. Schwartz WJ, Lydic R, Moore-Ede MC. In vivo metabolic activity of the suprachiasmatic nuclei: non-uniform intranuclear distribution of 14C-labeled deoxyglucose uptake. Brain Res. 1987 Oct 27; 424(2):249-57.
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        60. Schwartz WJ, Gross RA, Morton MT. The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker. Proc Natl Acad Sci U S A. 1987 Mar; 84(6):1694-8.
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        61. Reppert SM, Henshaw D, Schwartz WJ, Weaver DR. The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain. Brain Res. 1987 Feb 17; 403(2):398-402.
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        62. Schwartz WJ. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia. Am J Physiol. 1987 Feb; 252(2 Pt 2):R419-22.
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        63. Reppert SM, Schwartz WJ. Maternal endocrine extirpations do not abolish maternal coordination of the fetal circadian clock. Endocrinology. 1986 Oct; 119(4):1763-7.
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        64. Reppert SM, Schwartz WJ. Maternal suprachiasmatic nuclei are necessary for maternal coordination of the developing circadian system. J Neurosci. 1986 Sep; 6(9):2724-9.
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        65. Schwartz WJ, Busis NA, Hedley-Whyte ET. A discrete lesion of ventral hypothalamus and optic chiasm that disturbed the daily temperature rhythm. J Neurol. 1986 Feb; 233(1):1-4.
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        66. Schwartz WJ, Crosby G. Local cerebral glucose utilization in the homozygous Brattleboro rat. Neurosci Lett. 1985 Jul 31; 58(2):171-6.
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        67. Schwartz WJ, Stakes JW, Hobson JA. Transient cataplexy after removal of a craniopharyngioma. Neurology. 1984 Oct; 34(10):1372-5.
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        68. Aronin N, Difiglia M, Graveland GA, Schwartz WJ, Wu JY. Localization of immunoreactive enkephalins in GABA synthesizing neurons of the rat neostriatum. Brain Res. 1984 May 23; 300(2):376-80.
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        69. Reppert SM, Schwartz WJ. Functional activity of the suprachiasmatic nuclei in the fetal primate. Neurosci Lett. 1984 May 4; 46(2):145-9.
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        70. Reppert SM, Schwartz WJ. Maternal coordination of the fetal biological clock in utero. Science. 1983 May 27; 220(4600):969-71.
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        71. Schwartz WJ, Coleman RJ, Reppert SM. A daily vasopressin rhythm in rat cerebrospinal fluid. Brain Res. 1983 Mar 14; 263(1):105-12.
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        72. Reppert SM, Schwartz WJ, Artman HG, Fisher DA. Comparison of the temporal profiles of vasopressin and oxytocin in the cerebrospinal fluid of the cat, monkey and rat. Brain Res. 1983 Feb 21; 261(2):341-5.
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        73. Schwartz WJ, Hutchison HT, Berg BO. Computerized tomography in subacute necrotizing encephalomyelopathy (Leigh disease). Ann Neurol. 1981 Sep; 10(3):268-71.
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        74. Schwartz WJ, Davidsen LC, Smith CB. In vivo metabolic activity of a putative circadian oscillator, the rat suprachiasmatic nucleus. J Comp Neurol. 1980 Jan 1; 189(1):157-67.
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        75. Schwartz WJ, Smith CB, Davidsen L, Savaki H, Sokoloff L, Mata M, Fink DJ, Gainer H. Metabolic mapping of functional activity in the hypothalamo-neurohypophysial system of the rat. Science. 1979 Aug 17; 205(4407):723-5.
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        76. Schwartz WJ. A role for the dopaminergic nigrostriatal bundle in the pathogenesis of altered brain glucose consumption after lateral hypothalamic lesions. Evidence using the 14C-labeled deoxyglucose technique. Brain Res. 1978 Dec 8; 158(1):129-47.
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        77. Schwartz WJ. 6-Hydroxydopamine lesions of rat locus coeruleus alter brain glucose consumption, as measured by the 2-deoxy-D-[(14)C]glucose tracer technique. Neurosci Lett. 1978 Feb; 7(2-3):141-50.
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        78. Sharp FR, Schwartz WJ. Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep. Experientia. 1977 Dec 15; 33(12):1618-20.
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        79. Schwartz WJ, Gainer H. Suprachiasmatic nucleus: use of 14C-labeled deoxyglucose uptake as a functional marker. Science. 1977 Sep 9; 197(4308):1089-91.
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