Changes in neuronal activity and gene expression in guinea-pig auditory brainstem after unilateral partial hearing loss.
Spontaneous neural hyperactivity in the central auditory pathway is often associated with deafness, the most common form of which is partial hearing loss. We quantified both peripheral hearing loss and spontaneous activity in single neurons of the contralateral inferior colliculus in a guinea-pig model 1 week after a unilateral partial deafness induced by cochlear mechanical lesion. We also measured mRNA levels of candidate genes in the same animals using quantitative real-time PCR. Spontaneous hyperactivity was most marked in the frequency region of the peripheral hearing loss. Expression of glutamate decarboxylase 1 (GAD1), GABA-A receptor subunit alpha-1 (GABRA1), and potassium channel subfamily K member 15 (KCNK15) was decreased ipsilaterally in the cochlear nucleus and bilaterally in the inferior colliculus. A member of RAB family of small GTPase (RAB3A) was decreased in both ipsilateral cochlear nucleus and contralateral inferior colliculus. RAB3 GTPase activating protein subunit 1 (RAB3GAP1) and glycine receptor subunit alpha-1 (GLRA1) were reduced ipsilaterally in the cochlear nucleus only. These results suggest that a decrease in inhibitory neurotransmission and an increase in membrane excitability may contribute to elevated neuronal spontaneous activity in the auditory brainstem following unilateral partial hearing loss.
Physiology, School of Biomedical, Biomolecular and Chemical Sciences, M311, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, WA, Australia.
S
S
Dong
W H A M
WH
Mulders
J
J
Rodger
D
D
Robertson
D000200:Action Potentials; D000818:Animals; D003051:Cochlea / Q000293:injuries; D017626:Cochlear Nucleus / Q000503:physiopathology*; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D046088:Hearing Loss, Unilateral / Q000503:physiopathology*; D007245:Inferior Colliculi / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D020826:rab3A GTP-Binding Protein; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C104722:glutamate receptor ionotropic, AMPA 2