Diminished cortical inhibition in an aging mouse model of chronic tinnitus

• Published in: The Journal of neuroscience 2012-11, Vol.32 (46), p.16141-16148
• Main Authors: Llano, Daniel A, Turner, Jeremy, Caspary, Donald M
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Aging - physiology; Animals; Auditory Cortex - physiology; Auditory Threshold - physiology; Cerebral Cortex - physiopathology; Chronic Disease; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem - physiology; Flavoproteins - physiology; GABA Antagonists - pharmacology; gamma-Aminobutyric Acid - physiology; Hearing Loss, Noise-Induced - physiopathology; Male; Mice; Mice, Inbred CBA; N-Methylaspartate - physiology; Neural Inhibition - physiology; Pyridazines - pharmacology; Receptors, GABA-A - drug effects; Reflex, Startle - physiology; Tinnitus - physiopathology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.2499-12.2012

Flavoprotein autofluorescence imaging was used to examine auditory cortical synaptic responses in aged animals with behavioral evidence of tinnitus and hearing loss. Mice were exposed to noise trauma at 1-3 months of age and were assessed for behavioral evidence of tinnitus and hearing loss immediately after the noise trauma and again at ~24-30 months of age. Within 2 months of the final behavioral assessment, auditory cortical synaptic transmission was examined in brain slices using electrical stimulation of putative thalamocortical afferents, and flavoprotein autofluorescence imaging was used to measure cortical activation. Noise-exposed animals showed a 68% increase in amplitude of cortical activation compared with controls (p = 0.008), and these animals showed a diminished sensitivity to GABA(A)ergic blockade (p = 0.008, using bath-applied 200 nm SR 95531 [6-Imino-3-(4-methoxyphenyl)-1(6H)-p yridazinebutanoic acid hydrobromide]). The strength of cortical activation was significantly correlated to the degree of tinnitus behavior, assessed via a loss of gap detection in a startle paradigm. The decrease in GABA(A) sensitivity was greater in the regions of the cortex farther away from the stimulation site, potentially reflecting a greater sensitivity of corticocortical versus thalamocortical projections to the effects of noise trauma. Finally, there was no relationship between auditory cortical activation and activation of the somatosensory cortex in the same slices, suggesting that the increases in auditory cortical activation were not attributable to a generalized hyperexcitable state in noise-exposed animals. These data suggest that noise trauma can cause long-lasting changes in the auditory cortical physiology and may provide specific targets to ameliorate the effects of chronic tinnitus.