Photic Sensitivity of the Circadian Entrainment Pathway

Information

  • Research Project
  • 6599356
  • ApplicationId
    6599356
  • Core Project Number
    R15MH060122
  • Full Project Number
    2R15MH060122-02
  • Serial Number
    60122
  • FOA Number
    PA-99-62
  • Sub Project Id
  • Project Start Date
    8/1/1999 - 25 years ago
  • Project End Date
    3/31/2007 - 17 years ago
  • Program Officer Name
    NICHOLS, PAUL L
  • Budget Start Date
    4/1/2003 - 21 years ago
  • Budget End Date
    3/31/2007 - 17 years ago
  • Fiscal Year
    2003
  • Support Year
    2
  • Suffix
  • Award Notice Date
    -
Organizations

Photic Sensitivity of the Circadian Entrainment Pathway

DESCRIPTION (provided by applicant): Circadian pacemakers drive innumerable physiological and behavioral 24 h rhythms in almost all organisms - including humans. These pacemakers can be used to synchronize internal physiological processes and to anticipate or predict periodic environmental events. To be useful for organisms, however, endogenous circadian pacemakers must be synchronized or entrained to environmental time. The principal entraining agent for many pacemakers is the environmental light cycle and the process of photic entrainment has been well studied in mammals. Abnormalities in human circadian entrainment have been implicated in specific sleep disorders including advanced sleep phase syndrome, non-24h sleep-wake syndrome, as well as "jet lag" and disorders related to shift-work. Recently, significant components of the mammalian circadian pacemaker have been uncovered using the mouse as a model system. Several circadian genes have been identified and the interactions of these "clock" genes and their products appear to operate as a molecular feedback loop within neurons of the hypothalamic suprachiasmatic nucleus - the site of a mammalian circadian pacemaker. Among these genes mPer1 and mPer2 appear to play a crucial dual-role within the circadian mechanism -- acting as both integral clock genes as well as important components of the photic entrainment path-way -- the neural pathway that carries light information to reset and synchronize the molecular circadian mechanism. My long-term objectives include characterizing the functional operation of the photic pathway that mediates circadian entrainment in mPer2 mutant mice. Functional behavioral analyses provide an invaluable link between molecular analyses of the circadian clock and the operation of the pacemaker within intact animals. Experiments in this application focus upon 4 specific aims: 1) We will characterize the responsiveness of the photic entrainment pathway for the mPer2 and wild type mice at several phases of the circadian cycle. 2) We will directly compare two commonly used assays of circadian photic responsiveness (measured on circadian cycles 1 and 7 of constant darkness). Importantly this comparison will include both wild type as well as mPer2 mutant mice. 3) We will quantify the sensitivity of the photic entrainment pathway to the irradiance and duration of light pulses in mice carrying the mPer2(brdm1) mutation, comparing the characteristics of photic sensitivity measured for wild-type mice. 4) We will characterize entrainment of mPer2-mutant mice to complete LD cycles to determine how changes in photic sensitivity in mPer2(brdm1) mutant mice may influence the entrainment of the circadian pacemaker. Together these experiments will provide a comprehensive functional analysis of circadian photic responses in the mPer2 and wild type mice -- and furnish critical experimental tools for future dissections [of] the mammalian circadian mechanism and photic entrainment pathway at the cellular and molecular levels.

IC Name
NATIONAL INSTITUTE OF MENTAL HEALTH
  • Activity
    R15
  • Administering IC
    MH
  • Application Type
    2
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    130000
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    242
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIMH:130000\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF ST. THOMAS
  • Organization Department
    BIOLOGY
  • Organization DUNS
    606870090
  • Organization City
    ST PAUL
  • Organization State
    MN
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    55105
  • Organization District
    UNITED STATES