The influence of chronic lithium administration on deafferentation-induced cellular changes in the chick cochlear nucleus

Abstract

The avian brainstem serves as a useful model system to address the question of how afferent activity influences viability of target neurons. Approximately 20-30% of neurons in the avian cochlear nucleus, nucleus magnocellularis (NM) die following deafferentation (i.e., deafness produced by cochlea removal). Previous studies have identified cellular events that occur within hours following cochlea removal, which are thought to lead to the ultimate death of NM neurons. We have recently shown that chronic lithium treatment increases neuronal survival following deafferentation. To assess where in the cell death cascade lithium is having its effect, we evaluated some of the early deafferentation-induced cellular changes in NM neurons. Lithium did not affect deafferentationinduced changes that occur across the entire population of NM neurons. There were still deafferentation-induced increases in intracellular calcium concentrations and early changes in the ribosomes, as indicated by Y10b immunolabeling. Lithium did, however, affect changes that are believed to be indicative of the subpopulation of NM neurons that will eventually die. Ribosomes recovered in all of the deafferented NM neurons (as assessed by Y10b labeling) by 10 hours following cochlea removal in subjects pretreated with lithium, while a subpopulation of the NM neurons in saline-treated subjects showed dramatic reduction in Y10b labeling at that time. Lithium treatment also prevented the robust upregulation of Bcl-2 mRNA that is observed in a subpopulation of deafferented NM neurons 6 hours following cochlea removal. KeywordsAuditory system; Cell death; Bcl-2; Fura-2; Neuroprotection; Nucleus magnocellularis It is generally accepted that sensory experience plays an important role in the development of the brain. This idea is supported by studies showing changes in innervation patterns, or even cell death, following the loss of sensory experience in young animals (e.g. Catsicas et al., 1992;Pope and Wilson, 2007;Meisami and Safari, 1981). The effects of sensory deprivation have been extensively studied in the brainstem auditory system of the chick (Rubel et al., 1990). Loss of sensory input, produced by cochlea removal, results in the death of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. approximately 20-30% of the neurons in the ipsilateral cochlear nucleus, nucleus magnocellularis (NM) (Born and Rubel, 1985). NIH Public AccessThe brainstem auditory system of the chick has proven to be a fruitful model system for examining the effects of sensory deprivation, in part, because of its relatively simple or...

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