It is generally accepted that early experience is important for optimal development of the nervous system. Support for this notion stems largely from studies showing that sensory deprivation results in neuronal atrophy. During development, afferent input regulates the metabolic activity of postsynaptic neurons and is crucial for cell survival. The general aims of this proposal are to identify the signaling cascades by which afferent activity regulates the integrity of postsynaptic neurons. The model system used for these studies is the brain stem auditory system of the chick. Neurons in the cochlear nucleus, nucleus magnocellularis (NM), receive their sole excitatory input from the ipsilateral auditory nerve. Eliminating auditory nerve activity (e.g., by cochlea removal) results in death and atrophy of NM neurons. Activity-dependent changes in neuronal metabolism are observed within an hour after cochlea removal, and by 6 hrs, a subpopulation of neurons (approx. 30 percent) can be identified as those destined to die. The proposed experiments use both in vivo and in vitro methods to investigate the signaling cascades involved in determining the ultimate fate (life or death) of deafferented neurons. Three lines of research will be pursued. First, afferent regulation of genes, which are known to regulate cell death in other systems, will be explored in detail. Specifically, bcl-2 expression is up-regulated in a subpopulation of neurons by 6 hrs after deafferentation. Studies will determine the conditions necessary for the up-regulation of this gene, and the potential role of bcl-2 in regulating deafferentation-induced cell death. Second, the neurotransmitter receptors controlling an early activity- dependent effect in this system, the regulation of ribosomal integrity, will be more accurately defined. These studies will primarily focus on the role of metabotropic glutamate receptors. A final set of studies will explore normative features of a second neurotransmitter system, GABA, which is present in the brain stem auditory pathways. Avian brain stem auditory neurons have an unusual response to GABA, and the proposed studies will determine the mechanisms underlying this response. Additional experiments will describe a relatively uncharacterized population of GABAergic cells in this system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000858-13
Application #
6516097
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Freeman, Nancy
Project Start
1992-09-01
Project End
2006-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
13
Fiscal Year
2002
Total Cost
$265,720
Indirect Cost
Name
Florida State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
020520466
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
Stincic, T L; Hyson, R L (2011) The localization and physiological effects of cannabinoid receptor 1 in the brain stem auditory system of the chick. Neuroscience 194:150-9
Carzoli, Kathryn L; Hyson, Richard L (2011) In vivo analysis of the role of metabotropic glutamate receptors in the afferent regulation of chick cochlear nucleus neurons. Hear Res 272:49-57
Bush, A L; Hyson, R L (2006) Lithium increases bcl-2 expression in chick cochlear nucleus and protects against deafferentation-induced cell death. Neuroscience 138:1341-9
Nicholas, A H; Hyson, R L (2006) Afferent regulation of oxidative stress in the chick cochlear nucleus. Neuroscience 140:1359-68
Hyson, Richard L (2005) The analysis of interaural time differences in the chick brain stem. Physiol Behav 86:297-305
Nicholas, Alexander H; Hyson, Richard L (2004) Group I and II metabotropic glutamate receptors are necessary for the activity-dependent regulation of ribosomes in chick auditory neurons. Brain Res 1014:110-9
Wilkinson, B L; Jeromin, A; Roder, J et al. (2003) Activity-dependent regulation of the subcellular localization of neuronal calcium sensor-1 in the avian cochlear nucleus. Neuroscience 117:957-64
Wilkinson, B L; Elam, J S; Fadool, D A et al. (2003) Afferent regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus. Neuroscience 120:1071-9
Wilkinson, Brandy L; Sadler, Karen A; Hyson, Richard L (2002) Rapid deafferentation-induced upregulation of bcl-2 mRNA in the chick cochlear nucleus. Brain Res Mol Brain Res 99:67-74
Soares, Daphne; Chitwood, Raymond A; Hyson, Richard L et al. (2002) Intrinsic neuronal properties of the chick nucleus angularis. J Neurophysiol 88:152-62

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