Ph.D., Rutgers University, 1972
General Area of Research
Our behavior is systematically affected by neural, hormonal and immune system signals of which we are not aware.
Clocks inside of us
Almost anything you can mention fluctuates on a regular daily cycle. Human physiological patterns would appear to be dictated by the rising and setting of the sun. Unless we take on graveyard shift work, our habits surrounding eating, sleeping, activity, work, body temperature, hormonal fluctuations, wakefulness, and even learning ability seem to coincide with the 24-hour daily cycle of light and darkness. However, if you go into a cave with no external cues, these things would still cycle”, indicating that the control for these behaviors is endogenously determined.
Understanding the circadian clock will enable the design treatments and behavioral routines that work with internal clocks, not against them”. On a practical level, these natural temporal patterns keep us regulated so that we don’t get hungry or need to go to the bathroom in the middle of the night, or so we don’t fall asleep in the middle of the workday. Shift workers, for example, who account for 25% of the American workforce – regularly work against these endogenous clocks. “These people are always playing catch-up”, said Silver, “which can be dangerous given that shift workers provide some of society’s most critical services, such as health care, law enforcement, or rescue transportation.” Clearly one would not want to fly with a pilot who was severely jet-lagged.
It is not just performance, but also learning that can be affected by circadian rhythms. According to Silver, learned tasks are best performed if animals are tested at the same time of day that they originally learned the behavior. “This is why I try to give my tests at regular class time”, she added. Furthermore, Silver added that disrupting this regular cycle can even cause retrograde amnesia. The persistence of our endogenous circadian clocks has powerful implications for individuals as well as society. And so to understand how best to harness the power of these clocks, it is important that we understand how they work.
Sentinels of the brain-body interface: Mast cells
The Silver lab studies the role of mast cells in the brain. Mast cells are best known for their role in allergic reactions and anaphylaxis. However, recent work shows that they also exist in the CNS and are pluripotent as to the possible secretory products they can release. Brain mast cells are always active, in that they secrete their potent mediators into the brain environment. The lab’s work shows that mast cells occur in specific brain regions (unlike other hematopoietic cells that traffic through the entire brain) that they are affected by the behavioral and immune status of the organism (rats and mice). For example, there is a marked increase in brain mast cells following a period of sexual behavior, or of stress.
Recently, it has become possible to specifically examine the role of mast cells apart from the contributions of other immune cells, by using a mast cell deficient mouse. With this model, any loss of function in the knockout animal can be examined in the mast cell reconstituted animal, and specific functions can be assigned to the mast cell, without the danger of confounding developmental effects. Definite proof of function is achieved by reconstituting the deficient animal with the missing cells. The availability of this model system has enabled us to examine in a highly specific way the ways in which brain mast cells change under various behavioral states, and how they regulate and are regulated by behavior.
Lesauter, J. Silver, R. Cloues, R. Witkovsky, P. (2011) Light exposure induces short- and long-term changes in the excitability of retinorecipient neurons in suprachiasmatic nucleus. J Neurophysiol. 106(2):576-588. PMC3154817
Silver, R. Balsam, P. Butler, M. Lesauter, J. (2011) Food anticipation depends on oscillators and memories in both body and brain. Physiol Behav. 104(4):562-571. PMC3378387.
Foley N, Tong TY, Foley D, LeSauter J, Welsh DK, Silver R. (2011) Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus. Eur J Neurosci. 33(10):1851–1865. PMC3423955.
Butler, M.P. LeSauter, J. Sichel, A.N. Silver, R. (2011) Targeted mutation of the calbindin D28k gene selectively alters nonvisual photosensitivity. Eur J Neurosci. 33(12):2299–2307. PMC2735465.
Mong, J. Baker, F. Mahoney, M. Ketema, P. Schwartz, M. Semba, K. Silver, R. (2011) Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Steroids. Journal of Neuroscience. 31(45):16107-16116. PMC3249406.
Hart, C.L. Marvin, C.B. Silver, R. Smith, E.E. (2011) Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review Neuropsychopharmacology. 37(3):586-608. PMC3260986
Butler, MP. Karatsoreos, IN. LeSauter, J. Silver, R. (2012) Dose-dependent effects of androgens on the circadian timing system and its response to light. Endocrinol. 153(5):2344-52. PMC3339642.
Butler, MP. Rainbow, MN. Rodriguez, E. Lyon, SM. Silver, R. (2012) Twelve hour days in the brain and behavior of split hamsters. Eur J. NeuroSc. 36(4):2556-66. PMC in process.
Nautiyal, K.M. Dailey, C.A. Jahn, J. Rodriguez, E. Son, N.H. Sweedler, J.V. Silver, R. (2012) Serotonin of mast cell origin contributes to hippocampal function. Eur J. NeuroSc. 36(3):2347-59. PMC in process.
Silver, R. and Witkovsky, P. (2012) Phase waves in the suprachiasmatic nucleus. Eur. J. NeuroSc. 35(9):1416.
LeSauter, J. Lambert, C. M. Robotham, M. R. Model, Z. Silver, R. and Weaver, D. R. (2012). Antibodies for assessing circadian clock proteins in the rodent suprachiasmatic nucleus. PLoS ONE. 7(4):e35938. PMC3338757.
Silver, R. and Rainbow, M. (2012) The suprachiasmatic nucleus and the circadian timekeeping system of the body. In HbNS, D.W. Pfaff, ed. Brain Res Revs. 33(1):34-77.
Knolhoff, A. M. Nautiyal, K. M. Nemes, P. Kalachikov, S. Morozova, I. Silver, R. Sweedler, J. V. (In Press) Metabolomic and transcriptomic measurements reveal alterations in the hippocampus of c-kit mutant mice. Analytic Chemistry.
Courses Frequently Taught
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