Acoustic trauma evokes hyperactivity and changes in gene expression in guinea-pig auditory brainstem.
Hearing loss from acoustic trauma is a risk factor for tinnitus. Animal models using acoustic trauma have demonstrated hyperactivity in central auditory pathways, which has been suggested as a substrate for tinnitus. We used a guinea-pig model of unilateral acoustic trauma. Within the same animals, measurements of peripheral hearing loss, spontaneous activity of single neurons in the inferior colliculus and gene expression in cochlear nucleus and inferior colliculus were combined, acutely and after recovery from acoustic trauma. Genes investigated related to inhibitory (GABA-A receptor subunit alpha 1; glycine receptor subunit alpha 1) and excitatory neurotransmission (glutamate decarboxylase 1; glutamate receptor AMPA subunit alpha 2; glutamate receptor NMDA subunit 1), regulation of transmitter release (member of RAB family of small GTPase; RAB3 GTPase activating protein subunit 1) and neuronal excitability (potassium channel subfamily K member 15). Acoustic trauma resulted in unilateral hearing loss and hyperactivity bilaterally in inferior colliculus. Changes in expression of different mRNAs were observed in ipsilateral cochlear nucleus and in ipsi- and contralateral inferior colliculus, immediately after acoustic trauma, and after 2 and 4 weeks' recovery. Gene expression was generally reduced immediately after trauma, followed by a return to near normal levels or over-expression as recovery time increased. Different mechanisms appear to underlie the spontaneous hyperactivity observed. There is evidence of down-regulation of genes associated with neuronal inhibition in the contralateral inferior colliculus, whereas in ipsilateral cochlear nucleus, competing actions of inhibitory and excitatory systems seem to play a major role in determining overall excitability.
Dong
Songyu
S
Physiology, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, WA, Australia.
Mulders
Wilhelmina H A M
WH
Rodger
Jennifer
J
Woo
Samantha
S
Robertson
Donald
D
D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials; D000818:Animals; D001933:Brain Stem / Q000503:physiopathology; D017626:Cochlear Nucleus / Q000503:physiopathology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D015870:Gene Expression; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000503:physiopathology*; D006320:Hearing Tests; D007245:Inferior Colliculi / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013997:Time Factors
D012333:RNA, Messenger