Eric L. Bittman
Professor Emeritus, Biology
B.A., University of Pennsylvania, 1973
Ph.D., University of California, Berkeley, 1978
Circadian rhythms are endogenous oscillations whose period in constant conditions is close to 24h. Environmental signals that ultimately arise from the spin of the earth set the internal clock through the process of entrainment. A master pacemaker in the suprachiasmatic nucleus of the hypothalamus (SCN) is required not only for rhythmicity of sleep and wakefulness, but also to insure optimal physiological function as incompatible events are scheduled to occur at different phases. The SCN receives a privileged retinal input and communicates with other brain areas and the rest of the body through a variety of projections. Cells throughout the brain and periphery express core circadian clock genes that engage in feedback loops to insure temporal coordination. One obvious indication of the importance of circadian organization is the deleterious effects of jet lag and schedule changes experienced by shift workers: many illnesses are aggravated, including mental illness, diabetes, and heart disease.
We have discovered a novel circadian mutation called duper, which causes the circadian clock to run fast and reduces jet lag 4-fold. In a model of cardiomyopathy, duper mutant hamsters experience a striking resistance to the deterioration of heart function that is normally triggered by repeated shifts of the light:dark cycle. It appears that the mutation affects the SCN pacemaker rather than cell autonomous circadian oscillators. We are working to elucidate the nature of the mutation and its effect upon the brain and other organs.
Another critical function that is regulated by the circadian pacemaker is the discharge of luteinizing hormone from the anterior pituitary that triggers ovulation. Disruption of the circadian clock in any of several cell types in identified hypothalamic circuits alters timing of the LH surge. We are working to determine the relative contributions of circadian function in vasopressin, VIP, kisspeptin and GnRH neurons in order to reveal the loci at which the clock controls ovulation. We use molecular genetics to achieve conditional deletion of critical circadian clock genes in specific neurons of female mice. Chemogenetics allows us to silence neurons at specific loci and at particular times of day in order to determine when and where circadian signals control neuroendocrine function.
Bahiru, MS, Bittman EL. 2023. Adult Neurogenesis is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters. eNeuro 10(3):ENEURO.0359-22.2023. doi: 10.1523/ENEURO.0359-22.2023.
Sisson C, Bahiru MS, Manoogian ENC, Bittman EL 2022. The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease. Proc Natl Acad Sci U S A. (2022) 119(32):e2121883119. doi: 10.1073/pnas.2121883119. PMCID: PMC9371649.
Lee YY, Cal-Kayitmazbatir S, Francey LJ, Bahiru MS, Hayer KE, Wu G, Zeller MJ, Roberts R, Speers J, Koshalek J, Berres ME, Bittman EL, Hogenesch JB 2022. duper is a null mutation of Cryptochrome 1 in Syrian hamsters. Proc Natl Acad Sci U S A. 119(18):e2123560119. doi: 10.1073/pnas.2123560119. PMCID: PMC9170138.
Bittman EL 2022. Anatomical Methods to Study the Suprachiasmatic Nucleus. Methods Mol Biol. 2482:191-210. doi: 10.1007/978-1-0716-2249-0_13. PMID: 35610428.
Bittman EL. 2021. Entrainment Is NOT Synchronization: An Important Distinction and Its Implications. J Biol Rhythms 36(2):196-199. doi: 10.1177/0748730420972817. PMCID: PMC9235037.
Bittman, EL 2019. Circadian function in multiple cell types is necessary for proper timing of the preovulatory LH surge. J. Biol Rhythms, in press.
Manoogian ENC, Kumar A, Obed D, Bergan J, Bittman EL. 2018. Suprachiasmatic function in a circadian period mutant: Duper alters light- induced activation of vasoactive intestinal peptide cells and PERIOD1 immunostaining. Eur J Neurosci. 48(11):3319-3334. doi: 10.1111/ejn.14214. PMID:30346078
Bittman EL 2016. Circadian Rhythms: Understanding the SCN Connectome. Curr Biol. 2016 26(18):R840-R843. doi: 10.1016/j.cub.2016.08.007. PMID:27676300
Bittman EL 2016. Timing in the Testis.J Biol Rhythms. 31(1):12-36. doi: 10.1177/0748730415618297. PMID: 26656623
Manoogian, ENC, Leise, TL, and Bittman, EL, 2015. Phase resetting in duper hamsters: Specificity to photic zeitgebers and circadian phase. J Biol Rhythms, 30(2):129-143. doi: 10.1177/0748730414568297. PMID: 25633984
Bittman, E.L., 2014. Effects of the Duper Mutation on Responses to Light: Parametric and Non-parametric Responses, Range of Entrainment, and Masking. J. Biol. Rhythms, 29: 97-109 (Doi: 10.1177/0748730413520399).
Manoogian, E.N.C., Leise, T.L., and Bittman, E.L., 2014. Phase resetting in duper hamsters: Specificity to photic zeitgebers and circadian phase. J Biol. Rhythms, in press.
Mahoney, C.E., McKinley Brewer, J., and Bittman, E.L. 2013. Central control of circadian phase in arousal-promoting neurons. PLoS ONE , 8(6): e67173. (Doi: 10.1371/journal.pone.0067173).
Bittman, E.L., Kilduff, T.S., Kriegsfeld, L.J., Szymusiak, R., Toth, L.A., and Turek, F.W. 2013. Animal care practices in experiments on biological rhythms and sleep. J. Amer. Assn. Lab Animal Sci., 52: 437-443.
Bittman, E.L., 2012. Does the precision of a biological clock depend upon its period? Effects of the duper and tau mutations in Syrian hamsters. PLoS One, 7(5): e36119. PMID: 22615753
Monecke, S., McKinley Brewer, J., Krug, S., Bittman, E.L. 2011. Duper: a mutation that shortens hamster circadian period.J. Biol. Rhythms, 26: 283-292. PMID21775287
Krug, S., Brewer, J.M., Bois, A.S., Bittman, E.L. 2011. Effects of the Duper mutation on circadian responses to light. J. Biol. Rhythms, 26:293-304. PMID 2177587
Mahoney, C.E., Brewer, D., Costello, M.K., Brewer, J.M., and Bittman, E.L. 2010. Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase. Amer. J. Physiol. Reg. Integ. Comp. Physiol. 299: R751-61. PMID: 20592176
Bittman, E.L. 2009. Vasopressin: more than just an output of the circadian pacemaker? Amer. J. Physiol. Reg. Integ. Comp. Physiol. 296: R821-3. PMID 19109364
Bittman, E.L. , Costello, M.K., and Brewer, J.M., 2007. Circadian organization of tau mutant hamsters: Aftereffects and splitting. J. Biol. Rhythms, 22: 425-431. PMID17876063
Guo, H., Brewer, J.M., Lehman, M.N., and Bittman, E.L. 2006. Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker. Journal of Neuroscience, 26: 6406-12.
Guo, H., Brewer, J.M., Champhekar, A., Harris, R.B.S., and Bittman, E.L. 2005. Differential Control of Peripheral Circadian Rhythms by Suprachiasmatic-dependent Neural Signals. Proc. Natl. Acad. Sci. 102: 3111-6.
Cheng, M.Y., Bittman, E.L., Hattar, S.S., Leslie, F., Yau, K-W, and Zhou, Q-Y. 2005. Light regulation of prokineticin 2 molecular rhythm in the suprachiasmatic circadian clock. BMC Neurocience, 17: 6-17.
Tetel M.J., Ungar, T.C., Hassan, B., and Bittman, E.L. 2004. Photoperiodic regulation of androgen receptor and steroid receptor coactivator-1 in Siberian hamster brain. Brain Research, Molecular Brain Research, 131: 79-87.
Tong, Y, Guo, H., Brewer, J.M., Lee, H, Lehman, M.N., and Bittman, E.L. 2004. Oscillating expression of haPer1 and haBmal1 in peripheral organs of Syrian hamsters. J. Biol. Rhythms. 19: 113-125. MEDLINE
Bittman, E.L., Doherty, L., Huang L., and Paroskie, A. 2003. Period gene expression in mouse endocrine tissues. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285: R561-569. MEDLINE
Bittman, E.,L., Ehrlich, D.A., Ogdahl, J.L., and Jetton, A.E. 2003. Photoperiod and testosterone regulate androgen receptor immunostaining in the Siberian hamster brain. Biol. Reprod. 69: 876-884. MEDLINE
Huang, L., and Bittman, E.L. 2002. Olfactory bulb cells generated in adult male golden hamsters are specifically activated by exposure to estrous females. Hormones and Behavior, 41: 343-50.
Fukuhara, C., Brewer, J.M., Dirden, J.C., Bittman, E.L., Tosini G., and Harrington, M.E. 2001. Neuropeptide Y rapidly reduces Period 1 and Period 2 mRNA levels in the hamster suprachiasmatic nucleus. Neuroscience Letters, 314: 119-122.
Song, C.K., Bartness, T.J., Petersen, S.L., and Bittman, E.L. 2000. Co-expression of melatonin (MEL1a) receptor and arginine vasopressin mRNAs in the Siberian hamster suprachiasmatic nucleus. J. Neuroendocrinol. 12: 627-634. MEDLINE