The study of circadian rhythms in mammals allows us to address a broad spectrum of important questions in neuroscience involving cellular communication and the role of neuropeptides. We will focus on two important questions; 1) how VIP regulates intercellular communication and membrane excitability, and 2) how an attenuation or lack of the VIP signal affects circadian rhythms in physiology. The first question will be addressed by examining the effects of the VIP on gamma-aminobutyric acid (GABA)-evoked and intrinsic voltage-sensitive K+ currents in SCN neurons. The second question will be addressed by investigating animals that are deficient in VIP and determining how this disruption affects neuronal physiology. Mounting evidence from a variety of systems indicates that neuropeptides are present at many synaptic connections throughout the central nervous system (CNS), though their function is not completely understood. Understanding the mechanisms underlying VIP's effect on cellular excitability and communication in the SCN will provide us with a physiological explanation for many of the properties of not only circadian systems, but neuronal networks throughout the CNS. The whole-cell voltage-clamp recording techniques will be used to measure spontaneous synaptic currents and intrinsic membrane currents in SCN neurons visualized by infrared differential interference contrast (IR-DIC) videomicroscopy in a brain slice preparation of the C57bl mouse. Single-cell reverse transcription-PCR (RT-PCR) and immunocytochemistry will be used to identify the neuronal subtype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30MH068087-01
Application #
6646255
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Desmond, Nancy L
Project Start
2003-03-07
Project End
2005-03-06
Budget Start
2003-03-07
Budget End
2004-03-06
Support Year
1
Fiscal Year
2003
Total Cost
$27,274
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Itri, Jason N; Vosko, Andrew M; Schroeder, Analyne et al. (2010) Circadian regulation of a-type potassium currents in the suprachiasmatic nucleus. J Neurophysiol 103:632-40
Itri, Jason N; Michel, Stephan; Vansteensel, Mariska J et al. (2005) Fast delayed rectifier potassium current is required for circadian neural activity. Nat Neurosci 8:650-6
Itri, Jason; Colwell, Christopher S (2003) Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus. J Neurophysiol 90:1589-97