title: Deafness-related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity.
abstract: The inferior colliculus (IC) is a major center of integration in the ascending as well as descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play a key role. When normal input to the auditory system is decreased, the balance between excitation and inhibition in the IC is disturbed. We examined global changes in gene expression in the rat IC 3 and 21 days following bilateral deafening, using Affymetrix GeneChip arrays and focused our analysis on changes in expression of neurotransmission-related genes. Over 1400 probe sets in the Affymetrix Rat Genome U34A Array were identified as genes that were differentially expressed. These genes encoded proteins previously reported to change as a consequence of deafness, such as calbindin, as well as proteins not previously reported to be modulated by deafness, such as clathrin. A subset of 19 differentially expressed genes was further examined using quantitative RT-PCR at 3, 21 and 90 days following deafness. These included several GABA, glycine, glutamate receptor and neuropeptide-related genes. Expression of genes for GABA-A receptor subunits beta2, beta3, and gamma2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor alpha1 initially declined and then later increased, while alpha2 increased sharply at 21 days. Glycine receptor alpha3 increased between 3 and 21 days, but decreased at 90 days. Of the neuropeptide-related genes tested with qRT-PCR, tyrosine hydroxylase decreased approximately 50% at all times tested. Serotonin receptor 2C increased at 3, 21, and 90 days. The 5B serotonin receptor decreased at 3 and 21 days and returned to normal by 90 days. Of the genes tested with qRT-PCR, only glycine receptor alpha2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptor beta3, GABA receptor gamma2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology/Head Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA. avrilhol@umich.edu
authors.forename: Avril Genene
authors.initials: AG
authors.lastname: Holt
authors.forename: Mikiya
authors.initials: M
authors.lastname: Asako
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lomax
authors.forename: James W
authors.initials: JW
authors.lastname: MacDonald
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Lomax
authors.forename: Richard A
authors.initials: RA
authors.lastname: Altschuler
mesh_terms: D000818:Animals; D003638:Deafness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007245:Inferior Colliculi / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009473:Neuronal Plasticity; D009479:Neuropeptides / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate / Q000378:metabolism; D018009:Receptors, Glycine; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014018:Tissue Distribution
chemical_list: D009479:Neuropeptides; D020033:Protein Isoforms; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D018698:Glutamic Acid