This action is to recommend funding for three years to study neurotransmitters in the ear. Cells in the nervous system make functional connections called synapses; a biochemical compound used to transmit information across a synapse is called a neurotransmitter. The synthesis, release, uptake and turnover of neurotransmitters play key roles in information processing; the regulation of these steps by other compounds thus modulate the information transfer. Not much is known about the neurotransmitters or neuromodulators in the inner ear, and this organ provides a model system with several neuroactive substances to study their possible interactions. This project will quantify the neurochemical interactions within the cochlea of the inner ear. The cochlea contains the auditory receptor cells which synapse on fibers of the auditory nerve that carry signals to the brain; in addition, there are fibers called efferents that carry signals from certain central brain regions out to the cochlea. The efferent pathway apparently acts to modulate the sensory transmission coming in to the auditory pathway. The auditory transmitter release may be affected, or the molecular receptor sites on the auditory nerve terminals may be affected by neuromodulators released from the efferent terminals. Thus this first synapse in the auditory pathway can be considered a "multitransmitter" synapse. The bony shell containing the cochlea and nerve will be used in situ as a perfusion chamber to study the release, degredation and receptor interactions of two major classes of neuromodulator candidates: the opioid peptides and acetylcholine. Liquid chromatography, radioimmune assays and radioreceptor assays will unambiguously identify and quantify the neuroactive substances sampled from the cochlear tissues. To study mechanisms of possible co- transmission, perfusion of this space will be used to collect neuroactive substances in response to stimulation, and to infuse specific substances that have known agonist or antagonist actions at the synaptic receptor sites. The Program in Sensory Physiology & Perception recommends funding this project because it uses a cleaver, novel preparation to clarify the biochemical mechanisms involved in the auditory system, and the principles elucidated are likely to be applicable to other interactions of neurotransmitters elsewhere in the brain.
