Light-Induced Responses of Slow Oscillatory Neurons of the Rat Olivary Pretectal Nucleus

Background: The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes. Methodology: To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX). Conclusions: We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillationpreserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firin

Attenuated Food Anticipatory Activity and Abnormal Circadian Locomotor Rhythms in Rgs16 Knockdown Mice

Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN), the master circadian light-entrainable oscillator (LEO) of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA) targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO)-driven elevated food-anticipatory activity (FAA) observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s)

Development and regeneration of the vertebrate brain

The vertebrate brain is hierarchically assembled about orthogonal axes using organizing centers that control cascades of signaling events. The reiterative generation of these centers at defined times, and in precise spatial locations, leads to the conversion of a contiguous and homogenous epithelial sheet into the most complex biological tissue in the animal kingdom. The critical events orchestrating the construction of a "typical" vertebrate brain are described. Attention is focused on specification of major brain regions common across the vertebrate phylogeny, rather than on the differentiation of constituent cell types and specific cytoarchitectures. By uncloaking the complex spatial interactions that unfold temporally during the build of the vertebrate brain, it becomes clear why regeneration of this tissue following injury is such a challenging task. And yet, while mammalian brains fail to regenerate, the brains of non-mammalian vertebrates, such as teleosts, reptiles and amphibians, can successfully reconstitute brain tissue following traumatic injury. Understanding the molecular and cellular bases of this remarkable regenerative capacity is revealing the importance of developmental programs, as well as exposing unexpected roles for extraneous processes such as inflammation. Recent discoveries are now fuelling hope for future therapeutic approaches that will ameliorate the debilitating consequences of brain injury in humans