Integrated Calendar

Sleep and circadian rhythms are functionally important in all vertebrates and sleep disorders affect millions of people worldwide. While we understand that the timing and quality of sleep are regulated by circadian and homeostatic processes, the function of sleep is still enigmatic. Increasing evidence points to a role for sleep in maintaining “synaptic homeostasis”. This hypothesis suggests increases in global synaptic strength during wakefulness followed by a decrease during sleep, primarily in memory-related circuits. Hypocretins/orexins (HCRT) are neuropeptides that are important sleep-wake regulators and HCRT deficiency causes narcolepsy in humans and mammalian models. We have functionally characterized the HCRT system in zebrafish, a diurnal transparent vertebrate that is ideally suited to study neuronal anatomy along with sleep and circadian rhythms in vivo. We use time-lapse two-photon imaging in living zebrafish of pre- and post-synaptic markers to determine the dynamics of synaptic modifications during day and night and after manipulation of candidate genes. Video-tracking systems are used to monitor activity and sleep in order to link changes in gene expression and synaptic plasticity with behavioral output. We have found a functional HCRT neurons-pineal gland circuit that is able to modulate melatonin production and sleep consolidation. Importantly, we observed clock-controlled rhythmic variation in synapse number in HCRT axons projecting to the pineal gland. Furthermore, we cloned NPTX2b (neuronal activity-regulated pentraxin, NARP), a protein implicated in AMPA receptor clustering, and showed that it is a clock-controlled gene that regulates rhythmic synaptic plasticity in HCRT axons as well as the sleep promoting effect of melatonin. These data provide real-time, in vivo evidence of circadian regulation of structural synaptic plasticity. Building on this experimental approach, we developed several transgenic lines expressing a variety of excitatory and inhibitory synaptic markers and neuronal activity tools using the GAL4-UAS system. This opens the possibility of studying synaptic plasticity in other circuits, such as those involved in memory formation and learning, which are known to be sleep-dependent in mammals. Such an approach offers the opportunity to study synaptic plasticity in response to pharmacological and behavioral challenges or after genetic manipulation of key synaptic proteins, with complementary monitoring of the resulting behavior in a living vertebrate.

I will present a new model for the formation and evolution of galaxies. I will first introduce the ingredients included in standard Semi-Analytical Models (SAMs), and will summarize the successes and limitations of such models. A different complementary approach will be presented which is conceptually simpler and closer to the halo model. In our approach all the processes which govern galaxy formation are set by the host halo mass and redshift, but the galaxies are evolved within the complex structure of dark-matter merger-trees. Although the physical 'recipes' are simple and smooth, the properties of galaxies vary significantly due to the merger-histories of their host halos. I will compare our approach to a standard SAM, and will also explore a set of very
different models which all fit the observational data well. This will be used to identify the observational constraint which could distinguish between different models, and to explore the level of uniqueness inherent in galaxy formation models.