Journal of Neuroscience, Vol 7, 3840-3849, Copyright © 1987 by Society for Neuroscience
Differential neuronal survival in the avian ciliary ganglion after chronic acetylcholine receptor blockade
SD Meriney, G Pilar, M Ogawa and R Nunez
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06268.
We have described in the preceding 2 papers the development of the
pharmacological and contractile properties of all targets of the ciliary
ganglion: the iris and ciliary body (Pilar et al., 1987), and the choroidal
coat (Meriney and Pilar, 1987). In this paper, we examine the chronic
effects of ACh receptor (AChR) blockade on ciliary ganglion neuron
survival. Nicotinic or muscarinic AChR blockers were administered daily to
developing chicken embryos during the normal neuronal death period in the
ciliary ganglion. The effects of the blockers on ganglionic and
neuromuscular transmission were assessed, and neuronal survival was assayed
by counting both the total number of ganglion neurons and the selectively
HRP-labeled ciliary neurons after the normal neuronal death period.
Blockade of ganglionic transmission decreases survival in both populations
of neurons. Blockade of neuromuscular muscular transmission increases
survival in the ciliary population, which innervates the striated iris and
ciliary body muscle. In contrast, blockade of synaptic activity has various
influences on the survival of the choroid population, which innervates the
smooth muscle of the choroid coat. Smooth muscle muscarinic receptor
blockade with atropine does not influence survival. At higher doses (which
block ganglionic transmission), atropine decreases choroid survival.
Survival of the choroid population is increased by nicotinic blockade with
75 micrograms alpha bungarotoxin (alpha BTX), but decreased by 12.5
micrograms alpha BTX. Two main conclusions arise from these studies.
Activation of postsynaptic AChRs in both the ganglion and the periphery are
important in the regulation of neuronal survival. These effects usually
occur in opposite directions: Blockade of ganglionic transmission decreases
neuronal survival, while paralysis of neuromuscular transmission increases
neuronal survival. This embodies the "balance" hypothesis (Cunningham,
1982) for neuronal survival, which states that motoneurons must balance
afferent and target interactions during a critical period after synapses
are formed in both regions. The present observations support this
hypothesis. However, although both ciliary and choroid neurons have been
shown to depend on the presence of the periphery for survival, target
muscle paralysis via AChR blockade rescues the ciliary neurons but does not
influence survival in the choroid population. Target-dependent regulation
of choroid neuron survival during the normal neuronal death period is
clearly different from the regulation of ciliary neuron survival.