Title

EXPERIMENTAL ANALYSIS OF THE COMPETITION FOR SURVIVAL AMONG DEVELOPING CILIARY GANGLION NEURONS

Date of Completion

January 1986

Keywords

Biology, Neuroscience

Degree

Ph.D.

Abstract

Naturally occurring neuronal death is a widespread phenomenon in embryogenesis. This normally dramatic reduction in cell number can, to varying degrees, be prevented by excess target tissue, trophic factor, or blockade of the neuromuscular junction. To understand the dependence of developing ciliary ganglion neurons on their targets, it was important to determine the developmental sequence of various characteristics in these tissues.^ The development and pharmacology of neuromuscular and ganglionic transmission is described. Ciliary neurons in the ciliary ganglion innervate the iris and ciliary body muscles of the eye. Synaptic activation of these muscles begins at about St 35 and is mediated via muscarinic ACh receptors on myoepithelial cells. By about St 38, Striated muscle cells develop, and nicotinic ACh receptors predominately mediate iris and ciliary body muscle responses to nerve stimulation.^ The choroid coat of the eye is a smooth muscle "sheet" which is innervated by the choroid population of the ciliary ganglion. Neuromuscular transmission in the choroid was shown to be possible by about St 35 and is mediated entirely via muscarinic ACh receptors throughout development.^ Experimental manipulations of synaptic activity in the ciliary ganglion system were performed during the normal neuronal death period by administering daily injections of nicotinic or muscarinic ACh receptor blockers to the embryo. In summary, blockade of transmission through the ciliary ganglion increased cell death in both populations of neurons. Neuromuscular blockage at striated muscle synapses delayed neuronal death in the ciliary population, but not in the choroid cell population, where neuromuscular synapses are made with smooth muscle. It is possible that smooth muscle does not respond to synaptic blockade in a manner that supports more neuronal survival.^ Since the effects of ACh receptor blockade on neuronal survival in the ciliary ganglion cannot always be predicted by target muscle activity, the site of action of these effects on neuronal survival was re-evaluated. In general, motoneurons must balance afferent input with target connections during a critical period after both afferent and neuromuscular synapses are made.^ Since opiate peptides have been shown to exist endogenously in preganglionic terminals onto both ciliary and choroid neurons, the opiate agonist morphine was administered daily to the developing chick embryo during the normal neuronal death period. This treatment dramatically increased neuronal survival in both populations of ciliary ganglion neurons, and this effect was completely blocked by naloxone. Morphine appears to regulate neuronal survival via an activity independent mechanism. ^