ROLE OF PEPTIDES IN OCULOMOTOR NEUROTRANSMISSION

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The parasympathetic component of the oculomotor pathway is responsible for a number of critical non-retinal ocular processes, including control of the light aperture, accommodation and regulation of blood flow t the retina. The cell bodies of autonomic ganglion cells in this pathway are located in the ciliary ganglion. All presynaptic terminals in the ciliary ganglion originate in the midbrain in the Edinger-Westphal nucleus. Acetylcholine, contained within these terminals, is the only proven neurotransmitter in the ganglion, acting at nicotinic receptors on postsynaptic ganglion cells. Substance P-like and leucine-enkephalin-like immunoreactivities have been localized within dense core vesicles in a majority of the cholinergic terminals in the avian ciliary ganglion, suggesting that these neuroactive peptides are released along with acetylcholine following nerve stimulation. The role of these peptides in neurotransmission in the oculomotor system is not known and will be examined in this proposal. Intact ciliary ganglia obtained from chick embryos and hatched chickens will be studied in an in vitro electrophysiological chamber. Intracellular and extracellular recording methods will be used to characterize non-nicotinic transmission in the ganglion. The effects of substance P and leucine-enkephalin will be examined by application of these and related peptides. Specific opioid antagonists will be used to reveal any endogenous opioid actions. The avian ciliary ganglion contains two distinct types of postsynaptic cells, the ciliary and choroid neurons. In addition, presynaptic terminals which form calyciform endings on the ciliary neurons can be impaled in this ganglion. The ability to record from presynaptic and postsynaptic neurons in the ganglion is of critical importance to the project, since we have shown that the neuroactive peptides present have effects on both sides of the ganglionic synapse. Using intracellular recording in a brain slice preparation, the effects of tachykinins and opioid peptides will be examined in the Edinger-Westphal nucleus, which is known to receive a substance P-positive innervation from the contralateral suprachiasmatic nucleus. Of particular interest will be a comparison of the peptide responses of cell bodies in the nucleus to those of their terminals within the ciliary ganglion. This proposal should provide important information on the role of endogenous neuroactive peptides in synaptic transmission in the oculomotor pathway. A number of clinical diseases of the eye involve defects in this system. These include some defects in accommodation, internal ophthalmoplegia and tonic pupil. In addition, the condition of the pupil is an important diagnostic sign in numerous ocular syndromes and in traumatic injuries to the head.