Grant: Operating Grant

James Nagy, physiology, is working to understand how electrical synapses in the brain contribute to normal central nervous system (CNS) function and to the development of CNS disease. Neuroscientists have identified numerous chemical messengers that nerve cells in the brain employ to communicate with each other. But recent research by Nagy and others indicates that electrical synapses are present in the central nervous system and Nagy¹s group is pioneering the idea that these types of synapses may be as important a means of communication as chemical transmission. Nagy¹s team is focusing on this mode of intercellular information transfer that occurs by direct contact between the cells at what are called gap junctions. Gap junctions form electrical synapses and mediate electrical transmissions between neurons. Nagy is working to understand the types and locations of neurons that form gap junctions, to identify the members of the gap junction forming connexin proteins that are produced in neurons, to identity proteins that as associated with electrical synapses, and to determine how these proteins regulate and contribute to the functions of electrical synapses. To achieve this, Nagy's group will use state-of-the-art imaging equipment allowing rapid and efficient visualization and mapping of gap junctions throughout the brain. In addition, he will use biochemical approaches, cell culture model systems and various drugs to manipulate gap junction associated proteins, and thereby discern how these proteins govern the operations of electrical synapses. This work is expected to open up entirely new possibilities for considering ways in which inappropriate or abnormal cell-cell communication in brain may contribute to various CNS diseases such as Parkinson¹s disease, schizophrenia, depression and epilepsy.