Synapses throughout the human brain are closely associated with glia. Yet, the role of glia in the development and maintenance of synapses has not been thoroughly investigated. Preliminary data from Dr. Barres' laboratory indicate that synapses formed in the absence of glia in vitro have low efficacy. Glial cells can strongly enhance the efficacy of these synapses. We propose to further characterize how glial cells enhance synaptic efficacy. In particular, we will test the hypothesis that glia enhance synaptic efficacy by increasing the probability of presynaptic transmitter release. We will investigate how glial cells regulate synaptic efficacy. a) Do glial cells regulate transmitter synthesis? b) Do glial cells regulate transmitter release? c) Is electrical activity required for the glial enhancement of synaptic efficacy? d) Do glial cells enhance presynaptic calcium currents? e) Do glial cells upregulate expression of one or more presynaptic proteins.
