The long term goal is to characterize some of the cellular mechanisms which endow the nervous system with the power to adapt to the changing needs of the organism. It is our premise that such neuronal plasticity results from changes in synaptic efficacy - the power with which one neuron signals to another. Of particular interest are changes in synaptic efficacy which have long time courses and which are use-dependent. While these mechanisms are likely to be employed by the brain for higher functions such as learning and memory, they may also play important adaptive roles in the peripheral nervous system. We propose to study the synapses of sympathetic ganglia - tissues which regulate cardiovascular function. These synapses exhibit many of the properties of synapses in the brain but can be studied in isolation and under much more rigorous experimental conditions. A brief period of presynaptic tetany results in a long term potentiation (LTP) of both nicotinic and muscarinic synaptic transmission in the superior cervical ganglion. Adrenergic agents, which play important roles in cardiovascular adaptations to stress, also induce LTP of cholinergic autonomic synapses. A multidiscipline approach is planned. Intracellular and extracellular electrophysiological methods will be employed to determine whether pre- or postsynaptic processes are being potentiated and what biophysical mechanisms are involved. Pharmacological techniques will be employed to identify the receptors which induce LTP. The cyclic nucleotides will be studied as second messenger systems by pharmacological and biochemical means for possible correlation to LTP.
