Grant: Project Grant

The brain has two main cell types - neurons and glia - and interactions between them are crucial for many processes involved in brain development and information processing. For example, their two-way communication regulates the number and types of cells that are produced, and influences how neurons communicate chemically with one another at their sites of contact called synapses. There is still much to learn about the interactions between neurons and different types of glia. We are particularly interested in how glia use Excitatory Amino Acid Transporters EAATs) to take up important chemical transmitters like glutamate from synapses, and to act as channels for the passage of chloride ions in and out of cells. Defects of EAATs are a common feature of a variety of disorders such as ataxia, stroke, epilepsy and neurodegenerative diseases. Historically there has been a dearth of tools to study and manipulate glial subtypes in the laboratory. We have spent several years generating and collecting such tools, and we have launched new approaches to study neuron-glial interactions. In particular we are using a genetically tractable model organism, the fruit fly, because it has a simple yet sophisticated brain and central nervous system (CNS) in which neurons and glia perform many of the same functions they do in humans. It is also easy to study how the CNS controls behaviors like movement and sleep. The fruit fly has two EAATs that predominate in two distinct subtypes of glia. In this proposal we are specifically addressing the following questions: What is the role of the EAAT1 chloride channel? How do mutations of the EAAT1 cause episodic ataxia? How is EAAT2 different from EAAT1, and what is the role of EAAT2 in controlling sleep?