Gary E. Pickard, PhD Professor Phone: 970-491-2150 Member Education |
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Research Interests -- Biological Rhythms
Circadian oscillations are a pervasive property of biological organization from plants to insects to humans. In vertebrates, three structures are capable of autonomous circadian oscillations: the pineal gland, the retina, and the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. My laboratory uses a variety of techniques, ranging from detection of rhythmic hormone secretion from isolated pineal cells in culture to analysis of behavioral circadian rhythms under a variety of experimental conditions, to determine the mechanisms by which circadian oscillators generate circadian rhythms, synchronize to the external day/night cycle, and convey temporal information to the organism.
The functional utility of the mammalian SCN circadian oscillator is derived from its ability to be synchronized or entrained to the 24 hr environmental day/night cycle. Entrainment provides for stable and appropriate phasing of the SCN circadian oscillator with the environment, thereby, in effect, enabling recognition of local time. Thus, the SCN circadian oscillator is said to function as a biological clock. In the absence of rhythmic photic cues (i.e. constant dark), the clock free-runs with a period slightly greater or less than 24 hr, drifting in and out of synchrony with the environment.
Understanding the processes by which retinal afferents reset the SCN clock will provide pharmacologic tools that may be used to treat sleep disorders, sleep disruption (as in jet lag or shift work) and some serious affective disorders. One aspect of our research is focusing on newly discovered photoreceptive neurons in the retina that express the novel vertebrate opsin, melanopsin. We are examining the physiology of these light sensitive ganglion cells by recording from them in vitro. We identify melanopsin-expressing ganglion cells using a novel transsynaptic viral tracing procedure using a recombinant pseudorabies virus expressing the reporter green fluorescent protein. Electron microscopic analyses are also underway using melanopsin antibodies to define the retinal circuitry that provides input to these cells.
Another aspect of our work has focused on the ascending serotonergic afferents to the SCN. Using behavioral pharmacological procedures, receptor binding techniques, electron microscopy and in situ hybridization, we are examining the role of 5HT receptors on modifying the effects of light on circadian behavior and gene expression. These studies also utilize knockout mice lacking specific 5HT receptors. Activation of 5HT receptors inhibits retinal input to the SCN.
Representative Publications
Pickard GE, Weber ET, Scott PA, Riberdy AF, Rea MA. 1996. 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. J Neurosci 16:8208-8220.
Pickard GE, Rea MA. 1997. Serotonergic innervation of the hypothalamic suprachiasmatic nucleus and photic regulation of circadian rhythms. Biol Cell 89:513-523.
Pickard GE, Smith BN, Belenky M, Rea MA, Dudek FE, Sollars PJ. 1999. 5HT1B receptor-mediated presynaptic inhibition of reginal input to the suprachiasmatic nucleus. J Neurosci 19:4034-4045.
Smith BN, Banfield BW, Smeraski CJ, Wilcox CL, Dudek FE, Enquist LW, Pickard GE. 2000. Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified CNS circuits. Proc Natl Acad Sci USA 97:9264-9269.
Smith BN, Sollars PJ, Dudek FE, Pickard GE. 2001. Serotonergic modulation of retinal input to the mouse suprachiasmiatic nucleus mediated by 5HT1B and 5HT7 receptors. J Biol Rhythms 16:25-38.
Belenky M, Pickard GE. 2001. Subcellular distribution of 5HT1B and 5HT7 receptors in the mouse suprachiasmatic nucleus. J Comp Neurol 432:371-388.
Pickard GE, Smeraski CA, Tomlinson CC, Banfield BW, Kaufman J, Wilcox CL, Enquist LW, Sollars PJ. 2002. Intravitreal injection of the attenuated pseudorabies virus PRV-Bartha results in infection of the hamster suprachiasmatic nucleus only by retrograde transsynaptic transport via autonomic circuits. J Neurosci 22:2701-2710.
Sollars PJ, Smeraski CA, Kaufman JD, Ogilvie MD, Provencio I, Pickard GE. 2003. Melanopsin and non-melanopsin expressing retinal ganglion cells innervate the hypothalamic suprachiasmatic nucleus. Vis Neurosci 20:601-610.
