It is reasonably well established that amino acids, such as glutamate and aspartate, can act as transmitters in a variety of neural systems, ranging from the vertebrate CNS to the invertebrate neuromuscular junction. However, examining the pharmacology of amino acid transmission in these neural systems is restricted by a) their complexity, and/or b) the inaccessibility of the presynaptic nerve terminal to direct experimentation. The squid stellate ganglion giant synapse is a unique preparation for the examination of an amino acid transmitting synpase. The pre- as well as the postsynaptic nerve terminals are of sufficient size for microelectrode penetration which has allowed a detailed examination of the physiology of transmitter release. The principal reason for the lack of pharmacological studies on this preparation is the formidable diffusion barrier between the synapse and the bathing medium. I have devised a technique of perfusing the ganglion that overcomes this diffusion barrier which should be useful in both the examination of the pharmacology of the synapse, and also the collection of the transmitter in the perfusate. The immediate aims of the present proposal are to: 1) Identify amino acids and other substances that show excitatory or inhibitory actions at the giant synapse; 2) Determine by intracellular recording, whether these agents act pre- or postsynaptically - in particular glutamate and kainate that have been suggested in other neural systems to have a presynaptic site of action and; 3) Identify substances released from the ganglion upon electrical excitation of the nerve leading into it. The long term goals are to identify the transmitter active at this synapse, and to examine the properties of amino acid transmission in a synapse comprising a single identifiable pre-synaptic axon synapsing onto an identified postsynaptic axon.