Biological Rhythms Workshop I: introduction to chronobiology.

In this chapter, we present a series of four articles derived from a Introductory Workshop on Biological Rhythms presented at the 72nd Annual Cold Spring Harbor Symposium on Quantitative Biology: Clocks and Rhythms. A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate environmental variation promotes optimal performance and survival. In the first article, Introduction to Chronobiology, we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s. Workshop Part IA provides an overview of the molecular basis for rhythms generation in several key model organisms, Workshop Part IB focuses on how biology built a brain clock capable of coordinating the daily timing of essential brain and physiological processes, and Workshop Part IC gives key insight into how researchers study sleep and rhythms in humans.

Biological Rhythms Workshop IB: neurophysiology of SCN pacemaker function.

Pacemakers are functional units capable of generating oscillations that synchronize downstream rhythms. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is a circadian pacemaker composed of individual neurons that intrinsically express a near 24-hour rhythm in gene expression. Rhythmic gene expression is tightly coupled to a rhythm in spontaneous firing rate via intrinsic daily regulation of potassium current. Recent progress in the field indicates that SCN pacemaking is a specialized property that emerges from intrinsic features of single cells, structural connectivity among cells, and activity dynamics within the SCN. The focus of this chapter is on how Nature built a functional pacemaker from many individual oscillators that is capable of coordinating the daily timing of essential brain and physiological processes.

GFP fluorescence reports Period 1 circadian gene regulation in the mammalian biological clock.

Endogenous cyclic activation of a specific set of genes, including Period 1 (Per1), drive circadian rhythms in the suprachiasmatic nucleus (SCN), a biological clock nucleus of the brain. We have produced transgenic mice in which a degradable form of recombinant jellyfish green fluorescent protein (GFP) is driven by the mouse Period 1 (mPer1) gene promoter. GFP protein is expressed in the circadian neural structures of the retina and SCN. Fluorescent signals are resolved at the level of individual neurons. mPer1-driven GFP fluorescence intensity reports light-induction and circadian rhythmicity in SCN neurons. This circadian reporter transgene captures the gene expression dynamics of living biological clock neurons and ensembles, providing a novel view of this brain function.

D2 dopamine receptor involvement in the rough-and-tumble play behavior of juvenile rats.

By using dorsal contacts and pinning to quantify play behavior in juvenile rats, it was found that the D2 agonist, quinpirole, reduced both measures of play at doses greater than 0.05 mg/kg. Eticlopride, a D2 antagonist, also reduced both measures of play and blocked the reduction caused by quinpirole. The effect of quinpirole on play was largely unaffected by concurrent administration of either a D1 agonist (SKF 38393) or a D1 antagonist (SCH 23390), suggesting that D1 and D2 receptors are functionally independent with respect to play behavior. Quinpirole also reduced overall activity, suggesting that the effects on play may not be selective to neural circuitry responsible for play behavior. Although low doses of quinpirole (0.001--0.03 mg/kg) had a tendency to increase pinning, this effect was not very robust. These data suggest that D2 dopamine receptors may not have a major role in the control of play behavior in juvenile rats.

Effects of alpha-2 adrenoceptor antagonists on rough-and-tumble play in juvenile rats: evidence for a site of action independent of non-adrenoceptor imidazoline binding sites.

The pharmacological specificity of alpha-2 adrenoceptor involvement in the modulation of rough-and-tumble play behavior was assessed in juvenile rats. The alpha-2 adrenoceptor antagonists idazoxan and RX821002 both increased the frequency of pinning in individually housed rats that were given a brief opportunity to play. Dorsal contacts, a measure of play solicitation, were not consistently affected by these compounds. Since RX821002 shows little affinity for non-adrenoceptor imidazoline binding sites, it is likely that the facilitation of play following administration of these two compounds is due to blockade of alpha-2 receptors. The effect of RX821002 and idazoxan is unlikely to be an artifact associated with using rats that are reared in isolation, as RX821002 also increased pinning, as well as dorsal contacts, in group-housed rats that were isolated for a short period (4h) before the play session. The alpha-1 adrenoceptor antagonist prazosin, which also binds to alpha-2B receptors, reduced the frequency of both pinning and dorsal contacts. There was a strong trend for St 587, a centrally active alpha-1 agonist, to attenuate the effect of prazosin on play. While this leaves open the possibility that prazosin may be reducing play through alpha-1 blockade, antagonist activity at alpha-2B receptors cannot be ruled out. From these data, we conclude that the facilitation of play following idazoxan and RX821002 is likely due to blockade of alpha-2A adrenoceptors. These findings add further support for a specific role of alpha-adrenoceptors in the modulation of playfulness in the juvenile rat.