Eric L. Bittman
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 both cell autonomous circadian oscillators and the brain’s master paemaker. The mutation is an allele of the core clock gene Cryptochrome 1, but the phenotype of mutant hamsters differs in unexpected ways from that of Cry1-null mice.
Another critical function that is regulated by the circadian pacemaker is the discharge of luteinizing hormone from the anterior pituitary that triggers ovulation. We have found that 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.
B.A. University of Pennsylvania, 1973
Ph.D. University of California at Berkeley, 1978
Post-doctoral: University of Michigan, Ann Arbor, 1978-1982