Deafness‐related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity

• Published in: Journal of neurochemistry Vol. 93; no. 5; pp. 1069 - 1086
• Main Authors: Holt, Avril Genene, Asako, Mikiya, Lomax, Catherine A., MacDonald, James W., Tong, Ling, Lomax, Margaret I., Altschuler, Richard A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2005; Blackwell; Blackwell Publishing Ltd
• Subjects: Animals; auditory brainstem; Biological and medical sciences; Deafness; Deafness - genetics; Deafness - metabolism; Deafness - physiopathology; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Profiling; Glutamic Acid - metabolism; immunocytochemistry; Immunohistochemistry; Inferior Colliculi - metabolism; Inferior Colliculi - physiopathology; Male; Medical sciences; microarray; Molecular and cellular biology; Molecular genetics; Neuronal Plasticity; Neuropeptides - metabolism; neurotransmitter; Neurotransmitters; Non tumoral diseases; Oligonucleotide Array Sequence Analysis; Otorhinolaryngology. Stomatology; Protein Isoforms - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Receptors, GABA - metabolism; Receptors, GABA-A; Receptors, Glutamate - metabolism; Receptors, Glycine; Reverse Transcriptase Polymerase Chain Reaction - methods; RT–PCR; Tissue Distribution; Clathrin; auditory brainstem; Rat; Rodentia; Auditory disorder; immunocytochemistry; Glutamate receptor; Gene expression; Protein; Hearing loss; Gabaergic receptor; Vertebrata; microarray; Mammalia; Gene; Glycine receptor; RT-PCR; Plasticity; Neurotransmitter; ENT disease; Auditory pathway; Excitation; Neurotransmission
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03090.x

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 β2, β3, and γ2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor α1 initially declined and then later increased, while α2 increased sharply at 21 days. Glycine receptor α3 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 α2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptor β3, GABA receptor γ2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry.