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bioRxiv · 10.1101/2024.07.29.603150

Ototoxicity-related Changes in GABA Immunolabeling Within the Rat Inferior Colliculus

Holt, A. G.·Griffith, R. D.·Lee, S. D.·Asako, M.·Buras, E.·Yalcinoglu, S.·Altschuler, R. A.
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Abstract

Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat.The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation. There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al, 1995; Mossop et al, 2000; Salvi et al, 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78% in axodendritic and 82% in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness-diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.

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Holt, A. G., Griffith, R. D., Lee, S. D., Asako, M., Buras, E., Yalcinoglu, S., Altschuler, R. A.. 2024-07-30. Ototoxicity-related Changes in GABA Immunolabeling Within the Rat Inferior Colliculus. https://doi.org/10.1101/2024.07.29.603150

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