Research Summary

Identification and functional analysis of the mammalian "biological clock"

All organisms have internal biological clocks that serve to recognize local time of day and to temporally organize behavioral and physiological functions. Circadian rhythms continue to oscillate within an approximate 24-hour period in the absence of external cues, although ordinarily these rhythms are synchronized to the day-night cycle. The functional components of the "biological clock" include an input pathway that synchronizes to the environment, a pacemaker that generates the oscillation, and output pathways that control overt rhythms. The circadian system has marked implications for shift work and jet lag. Research in the lab uses a variety of neuroanatomical and molecular techniques to study this system, including neural tissue transplants, immunohistochemistry, in situ hybridization, PCR, cell and tissue culture, and reporter gene technology

Behaviorally triggered appearance of mast cells in the brain

We have discovered that sexual behavior triggers the appearance of mast cells in the brain of doves, and that sex steroids activate brain mast cells, causing them to release their contents. This is a new mode of communication between the immune, neural and endocrine systems. These immunocytes, serving as mobile single cell glands, are likely to be a phylogenetically ancient system that rapidly delivers otherwise unavailable biologically active materials to specific brain regions upon demand. Currently, we are working on understanding the function of brain mast cells in avian and mammalian species.

Selected Publications

1. Joseph LeSauter, Nawshin Hoque, Michael Weintraub, Donald W. Pfaff, and Rae Silver (2009) Stomach ghrelin-secreting cells as food-entrainable circadian clocks. PNAS August 11, 2009 vol. 106 no. 32 13582-13587

2. Elise Drouyer, Joseph LeSauter, Amanda L. Hernandez, Rae Silver (2009)"Specializations of Gastrin Releasing Peptide Cells of the Mouse Suprachiasmatic Nucleus." (submitted, J Comparative Neurology, 2009)

3. Joseph LeSauter, Taslima Bhuiyan, Takao Shimazoe and Rae Silver (2009) "Circadian Trafficking of Calbindin-ir in Fibers of SCN Neurons." J. Biological Rhythms (in press).

4. Matthew P. Butler and Rae Silver (2009) "Basis of robustness and resilience in SCN circuits: Individual neurons form circuits that repeat a daily sequence of activity to produce a cell based brain clock." J Biol Rhythms 2009; 24; 340-352

5. Yan, L., Silver, R. (2009) "Day-length encoding through tonic photic effects in the retinorecipient SCN region" European Journal of Neuroscience 28 (10), pp. 2108-2115.

6. Rae Silver and Joseph LeSauter (2008) "Circadian and Homeostatic Factors in Arousal." NY Acad. Sci. 1129: 263-274.

7. Nautiyal KM, Ribeiro AC, Pfaff DW, Silver R. (2008) "Brain mast cells link the immune system to anxiety-like behavior." Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):18053-7.

8. Ribeiro, AC, Sawa E, Carren-LeSauter I, LeSauter J, Silver R and Pfaff, DW (2008). "Two forces for arousal: Pitting hunger versus circadian influences and identifying neurons responsible for changes in behavioral arousal." Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20078-83.

9. Lily Yan, Ilia Karatsoreos, Joseph LeSauter, David K. Welsh Steve Kay, Duncan Foley, Rae Silver (2008) "Exploring Spatio-temporal Organization of SCN Circuits." Cold Spring Harb Symp Quant Biol. 2007;72:527-41. PMID: 18419312

10. Karatsoreos I, and Silver R (2007) "The neuroendocrinology of the uprachiasmatic nucleus as a conductor of body time in mammals" Endocrinology 148: 5487-5495.

11. Yan L, Bobula JM, Svenningsson P, Greengard P, Silver R. (2006) DARPP-32 involvement in the photic pathway of the circadian system." J Neurosci. 26:9434-9438.

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