Functions and Mechanisms of Sleep in Flies and Mammals

摘要

Work on sleep at Brandeis focuses on Drosophila melanogaster as well as the more traditional rodent models. The Drosophila works aims to exploit the genetic advantages of this organism yet still learn about aspects of sleep relevant to humans. The major finding has been that the human therapeutic Carbamazapine is a potent sleep-deprivation agent in flies. Current data indicate that its effects are mediated through the Rdl GABAA receptor, which has implications for the role of this drug in humans. One of the rodent laboratories is focused on the regulation of sleep and waking in the basal forebrain. The goal is to identify gene expression changes in its cholinergic neuronal subset, and specific neuron purification has been accomplished. Another rodent laboratory is studying the effects of sleep deprivation on the intrinsic electrophysiology and gene expression properties of neocortical neurons. Interesting changes in firing properties of layer 5 pyramidal neurons have been observed, and gene expression assays from these cells are underway. The final two projects involve the role of sleep in homeostatic plasticity and fear conditioning. These are being done both in vivo, in freely behaving animals, and 'ex vivo,' in cortical slices after sleep deprivation or training.