Differential neuronal survival in the avian ciliary ganglion after chronic acetylcholine receptor blockade

Abstract

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.

Synaptically Driven Calcium Transients via Nicotinic Receptors on Somatic Spines

“…The present results indicate that high-frequency signaling can produce sustained cell-wide calcium elevations, raising the possibility of excitotoxicity. Chronic exposure in ovo to nicotinic antagonists in general and ␣-Bgt in particular have pronounced and complex effects on neuronal survival and development in the ciliary ganglion (Meriney et al, 1987). It has not yet been possible, however, to dissect unambiguously the contributions of ganglionic receptors and peripheral muscle receptors to these events.…”

Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion NeuronsIn Vitro

“…Depolarization is an important trophic stimulus accounting, at least in part, for neurotrophic support by presynaptic cells; blockade of membrane electrical activity in vivo (Wright, 1981;Furber et al, 1987;Meriney et al, 1987;Maderdrut et al, 1988;Rubel et al, 1990;Catsicas et al, 1992;Galli-Resta et al, 1993) and in vitro (Lipton, 1986;Ruitjer et al, 1991) reduces neuronal survival. Depolarization permits neuronal survival in vitro in the absence of added neurotrophic factors (Scott and Fisher, 1970;Bennett and White, 1979;Chalazonitis and Fischbach, 1980;Wakade et al, 1983;Gallo et al, 1987).…”

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca2+]iwithin a Set Range

“…Blockade of afferent input increases death in vivo in central (Catsicas et al, 1992;Galli-Resta et al, 1993) and peripheral neurons (Wright, 1981;Furber et al, 1987;Meriney et al, 1987;Maderdrut et al, 1988). In the avian auditory system, removal of the cochlea causes rapid atrophic changes, culminating in a 25-30% loss of neurons in the target, nucleus magnocellularis (Born and Rubel, 1985;Steward and Rubel, 1985;Sie and Rubel, 1992); blockade of electrical activity results in rapid atrophic changes and loss of magnocellularis neurons comparable with those after complete cochlear ablation (Born and Rubel, 1988;Pasic and Rubel, 1989;Rubel et al, 1990;Sie and Rubel, 1992).…”