9407579 Mynlieff ABSTRACT Regulation of neurotransmitter release into the synaptic cleft is a primary means of achieving synaptic plasticity in the central nervous system. Since influx of calcium through voltage-dependent channels is necessary for neurotransmitter release, modulation of the activity of these channels by neurotransmitters is likely to be a common mechanism of regulating synaptic plasticity. There is currently no consensus on the identity of the calcium channel controlling excitatory or inhibitory neurotransmitter release, thus raising the possibility that different synapses may use different channel types. Future studies in Dr. Mynlieff's laboratory will exploit the well-characterized circuitry of the hippocampus to investigate the identity of the calcium channels by neurotransmitters. The first specific aim is to develop the techniques necessary to dissociate inhibitory interneurons from the hippocampus suitable for patch clamp studies. The second specific aim is to pharmacologically characterize the calcium currents present in different types of inhibitory interneurons using whole cell voltage clamp recording techniques. A thorough knowledge of the calcium channel pharmacology in various presynaptic cells is necessary before any studies are performed on the identity of the calcium channel(s) controlling release of neurotransmitters using the hippocampal slice preparation A thorough characterization of the calcium currents is also necessary before performing any studies on neuromodulation of these channels which may lead to changes in synaptic function. Many different neurotransmitters are known to modulate synaptic function and also to modulate calcium currents but it is not clear that these two events are related. By combining experiments in isolated presynaptic cells where the calcium currents can be easily ident ified with experiments in the hippocampal slice preparation where specific synapses can be stimulated in isolation Dr. Mynlieff hopes to make the connection between modulation of calcium currents and modulation of neurotransmitter release stronger. Although the future plans in Dr. Mynlieff's laboratory includes investigating both excitatory and inhibitory synapses in the hippocampus, the experiments outlined in this proposal concentrate on the inhibitory neurons because much less is known about the inhibitory presynaptic cells than the excitatory presynaptic cells in the hippocampus. Understanding how neurotransmitters regulate specific synapses by modulation of distinct calcium channel types will provide insight into some of the mechanisms of synaptic plasticity.
