The Modulation of Inhibitory Synapses During Development

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9308377 Sanes As the brain matures, the connection between nerve cells are gradually modified in response to the environment, similar to the mechanisms underlying learning and memory. Some of the connections between nerve cells become stronger, while others are eliminated altogether. The mechanisms by which these changes occur are beginning to be unraveled at one set of connections in the central nervous system, called excitatory connections. This set of connections is the sort found between a motor neuron and muscle cell, where one cell activates a second. However, nearly half of the neuronal connections in the brain are inhibitory, and we do not yet know whether these connection are modified during the development of the central nervous system. Since virtually every task that the brain performs utilizes both excitatory and inhibitory connections, it is essential to understand how the latter develop. The proposed study will investigate whether the strength of inhibitory connections is dependent upon experience during the course of brain maturation. In the central auditory system, it is possible to monitor the strength of identified inhibitory connections by examining the size of the electrical response when they are stimulated. This project will determine what happens to the electrical activity at these inhibitory connections when they are used or not used during the course of development. At a molecular level, it will be possible to determine whether the receptor molecules that mediate inhibitory activity are produced in appropriate number when these connections remain silent. A second experiment will determine whether the strength of inhibitory connections can be enhanced over the course of minutes by directly stimulating them at very high levels. Together, these experiments will demonstrate how the modification of inhibitory connections may lead to mature central nervous system function. *** CI Sound midimap.drv=MIDI Mapper timer.drv=Timer rv=Timer v=Timer timer.drv=Timer imer.dr9308377 Sanes As the brain matures, the connection between nerve cells are gradually modified in response to the environment ! ! ! F ( Times New Roman Symbol & Arial " h $ EÕ E 1 # @ sanes William Proctor, IBN William Proctor, IBN