9604499 Miledi Understanding how the brain works is, undoubtedly, one of the major scientific challenges of this century. This task is daunting not only by the sheer number of nerve cells that compose the nervous system, but also by the complexity of their interactions. Such interactions are fundamental to all functions of the brain. Therefore, it is imperative to understand fully how nerve cells communicate with one another in order to comprehend how the brain functions. Nerve cells (also called neurons) communicate by sending chemical signals termed neurotransmitters. The "sending" cell releases neurotransmitter molecules, which act upon neighboring "receiving" cells. There, neurotransmitters bind to specialized proteins called receptors. Neurotransmitters and receptors act much like a key and a lock: if there is a match, the receptors are activated, and the neuron is excited or inhibited. Neurons possess various types of receptors, each specific for a given neurotransmitter. The major type of inhibitory receptor in the brain is called GABAa, because these receptors recognize the neurotransmitter GABA. GABAa receptors are the target for a great variety of pharmaceutical drugs, including benzodiazepines and barbiturates. Recently, a new type of GABA receptor was discovered in the eye (which is an extension of the brain). This new type of receptors, called GABAc, features properties that make it very distinct from the two other types of GABA receptors that were known. Although GABAc receptors recognize GABA, they are not affected by benzodiazepines or barbiturates, unlike GABAc receptors. The aim of this project is to understand how the GABAc receptor works, by studying how its molecular structure influences its properties. This project will eventually lead to a better understanding of the role of this receptor in the eye and in the brain. In addition, this knowledge could prove very useful to rationally design new medicinal drugs that target specifically given types of GABA receptors.
