Naturally-occurring neuron death in the ciliary ganglion of the chick embryo following removal of preganglionic input: evidence for the role of afferents in ganglion cell survival

Abstract

With only a few exceptions, most investigations of the mechanisms involved in naturally-occurring neuron death have focused on interactions between neurons and their targets, with much less attention having been paid to the possible role of the afferent inputs in this phenomenon. This is true of the avian ciliary ganglion (CG), which is composed of a population of peripheral autonomic neurons that project to smooth and striated musculature in the eye and which receive afferents from a single source, the accessory oculomotor nucleus (AON), which is the avian homolog of the Edinger-Westphal nucleus. Although several lines of evidence strongly support the important role of targets in regulating the death and survival of CG neurons, the role of afferents has not yet been systematically examined. Following the destruction of the AON on embryonic day (E) 4, which is several days before the onset of normal cell death in the CG, we have found that by the end of the normal cell death period (E14-E15), 85–90% of the CG neurons degenerate and die, compared to 50% in controls. This is comparable to the amount of induced cell loss that occurs following removal of the optic vesicle containing the CG targets. The neurons surviving after deafferentation appear to be sustained by some influence from their targets since combined deafferentation and eye removal results in the loss of virtually all neurons in the CG. Following deafferentation of the CG on E4, the ganglion develops normally up to about E10, after which a precipitous loss of cells occurs. Based on several kinds of evidence (e.g., axon counts, silver stain, retrograde labeling of the CG), we conclude that the deafferented neurons project to and innervate their muscular targets in the eye. Therefore, the increased cell death following deafferentation cannot be due to the failure of deafferented neurons to contact their targets. The deafferented neurons undergo a normal sequence of initial ultrastructural differentiation. When they do begin to degenerate, the type of fine structural changes they exhibit appears indistinguishable from the degenerative changes observed in control embryos. Neurons in deafferented ganglia were occasionally observed to receive synaptic contacts, which we attribute to aberrant intraganglionic connections induced by deafferentation. These contacts probably play little, if any, role in the maintenance of neurons since, as noted above, following combined deafferentation and target deletion virtually all neurons degenerate and die.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulatory mechanisms that govern nicotinic synapse formation in neurons

“…The in vivo role of innervation in controlling nAChR expression was defined by in ovo microsurgical removal of the sole source of presynaptic inputs to chick CG neurons, the accessory oculomotor nucleus, prior to synaptogenesis (Furber et al, 1987;Engisch and Fischbach, 1992;Arenella et al, 1993;Levey et al, 1995;Brumwell et al, 2002). This surgery prevents innervation without direct damage to CG neurons or transection of their processes.…”

“…In the absence of inputs, these neurons are ultrastructurally and electrophysiologically normal (Engisch and Fischbach, 1992;Dourado et al, 1994;Levey et al, 1995). Importantly, input-deprived CG neurons still form synapses on target tissues (Furber et al, 1987), enabling characterization of the specific effects of presynaptic innervation on nAChR expression.…”

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).…”

Astrocyte and Muscle-Derived Secreted Factors Differentially Regulate Motoneuron Survival

“…Furthermore, even in the presence of MEx, which contains numerous trophic factors, not all MNs are rescued from naturally occurring or induced PCD, a result that suggests two possibilities that are not mutually exclusive (Oppenheim et al, 1988). One possibility, that the target is not the sole source of MN trophic support, has been discussed extensively (Okado and Oppenheim, 1984;Eagleson et al, 1985;Furber et al, 1987; fate of any given MN (Oppenheim, 1991;Pettmann and Henderson, 1998;Raoul et al, 2000;Ricart et al, 2006). Thus, augmenting the target size (or provision of MNs with increasing amounts of MEx) may result in the increased availability of both trophic and toxic factors, thereby making the rescue of all MNs impossible.…”

“…The number of MNs that die as a result of axotomy, limb amputation, and nerve crush is diminished as the organism ages, although it is unclear whether MNs become trophic-independent or, if with age, they come to depend on alternative sources of trophic support (Snider and Thanedar, 1989;Crews and Wigston, 1990). Numerous other putative trophic sources exist, including glia (e.g., Schwann cells and astrocytes), afferents, and components of the extracellular matrix (Okado and Oppenheim, 1984;Eagleson et al, 1985;Furber et al, 1987;Yin et al, 1994;Riethmacher et al, 1997;Arce et al, 1998;Wong et al, 1999). Astrocytes represent a significant, yet underappreciated, cellular population in the nervous system that contributes to numerous developmental processes.…”