klgamble@uab.edu
Education:
BA, Psychology, King College, Bristol, TN, 1996; Ph.D. Behavioral Neuroscience, Georgia State University, 2004; Postdoctoral Fellow, Vanderbilt University 2004-2009.
Academic Appointments with UAB:
- Assistant Professor of Psychiatry and Behavioral Neurobiology
- Faculty Member, Comprehensive Neuroscience Center
Research Interests:
Mechanisms and Entrainment of Circadian Clocks
The mammalian brain's primary biological clock (the suprachiasmatic nucleus or SCN) drives daily physiological and behavioral rhythms that persist in the absence of environmental time cues with a near-24 hour period. When the endogenous clock is misaligned with the external environment such as during jet lag and shift work, serious repercussions can result, not only for the circadian system but also for the entire body. For example, shift work is associated with an increased risk of gastrointestinal disorders, cardiovascular disease, depression, and cancer. Clinically, sleep and circadian rhythm disturbances have been linked to mood and developmental disorders. In fact, an interaction of several single nucleotide polymorphisms in circadian clock genes has recently been associated with bipolar disorder (Shi, J., et al, 2008). Given the range of circadian physiological processes, it is not surprising that ~24-hour rhythms in the expression of the core clock genes or electrical activity have been discovered throughout the brain and body. Therefore, determining underlying mechanisms for the types of stimuli that can "reset" and re-align the clock with the environment is important for developing novel therapeutic approaches.
The broad research interest of our laboratory is the process by which the SCN synchronizes with the external environment (entrainment). While both photic (light) and nonphotic cues (exercise, arousal, etc) can shift the phase of the clock, little is known about how these stimuli interact. Our laboratory is currently using circadian behavioral analysis, tissue-level imaging and pharmacology, as well as targeted fluorescence electrophysiology in two different transgenic reporter mouse models to investigate the neural circuitry of the SCN during the phase resetting process. In addition, we are investigating genotype/phenotype associations in shift-workers to determine significant gene-environment interactions. Altogether, the focus of this laboratory is to determine how genetic and environmental disruption of the circadian system can lead to mental illness and physiological dysfunction.
Recent Publications:
- Xu, X., Graeff, R., Xie, O., Gamble, K.L., Mori, T., and Johnson, C.H. (2009). Comment on: "The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop." Science, in press.
- Gamble, K.L. and Ciarleglio, C.M. (2009). Ryanodine receptors are regulated by the circadian clock and implicated in gating photic entrainment. J Neurosci, in press.
- Ciarleglio, C.M, Gamble, K.L., Axley, J.C., Strauss, B.R., Cohen, J., Colwell, C.S., and McMahon, D.G. (2009). Population Encoding by Circadian Clock Neurons Organizes Circadian Behavior. J Neurosci, 29(6), 1670-6.
- Ehlen, J. C., Novak, C. M., Karom, M. C., Gamble, K. L. & Albers, H. E. (2008). Interactions of GABAA Receptor Activation and Light on Period mRNA Expression in the Suprachiasmatic Nucleus. J Biol Rhythms 23, 16-25.
- Gamble, K.L., Allen, G., Zhou, T.R., and McMahon, D.G. (2007). Gastrin releasing peptide induces Per1 throughout the SCN and phase delays Per2-luc rhythms in a CREB-dependent manner. J Neurosci, 27(44), 12078-87.
- Ehlen, J.C., Novak, C.M., Gamble, K.L., Paul, K.N., and Albers, H.E. (2006). GABA-A receptor activation suppresses Period 1 mRNA and Period 2 mRNA in pattern similar to other nonphotic stimuli during the mid-subjective day. Eur J Neurosci, 23(12), 3328-36.
- Gamble, K.L., Paul, K.N., Karom, M.C., Tosini, G., and Albers, H.E. (2006). Paradoxical effects of NPY in the suprachiasmatic nucleus. Eur J Neurosci 23(9), 2488-94.
- Gamble, K.L., Ehlen, J.C., and Albers, H.E. (2005). Circadian control during the day and night: Role of neuropeptide Y Y5 receptors in the suprachiasmatic nucleus. Brain Res.Bull., 65(6), 513-519.
- Paul, K.N., Gamble, K.L., Fukuhara, C., Novak, C.M., Tosini, G., and Albers, H.E. (2004). Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels. Eur.J.Neurosci., 19, 2808-2814.
- Gamble, K.L., Novak, C.M., and Albers, H.E. (2004). Neuropeptide y and n-methyl-d-aspartic acid interact within the suprachiasmatic nuclei to alter circadian phase. Neuroscience, 126, 559-565.
- Gamble, K.L., Novak, C.M., Paul, K.N., and Albers, H.E. (2003) Tetrodotoxin blocks the circadian effects of NMDA during the day but not at night. Neuroreport 14(4), 641-644.