» Articles » PMID: 33925933

Overexpression of Under the Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2021 Apr 30
PMID 33925933
Citations 1
Authors
Affiliations
Soon will be listed here.
Abstract

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse () expressing under the promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these mice. In this study, we investigated how overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of mice and demonstrate that major changes occur on the side of inhibition.

Citing Articles

Candidate Key Proteins in Tinnitus-A Bioinformatic Study of Synaptic Transmission in the Inferior Colliculus.

Gross J, Knipper M, Mazurek B Int J Mol Sci. 2025; 26(5).

PMID: 40076458 PMC: 11899339. DOI: 10.3390/ijms26051831.


Harmony in the Molecular Orchestra of Hearing: Developmental Mechanisms from the Ear to the Brain.

Pyott S, Pavlinkova G, Yamoah E, Fritzsch B Annu Rev Neurosci. 2024; 47(1):1-20.

PMID: 38360566 PMC: 11787624. DOI: 10.1146/annurev-neuro-081423-093942.


ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization.

Filova I, Pysanenko K, Tavakoli M, Vochyanova S, Dvorakova M, Bohuslavova R Proc Natl Acad Sci U S A. 2022; 119(37):e2207433119.

PMID: 36074819 PMC: 9478650. DOI: 10.1073/pnas.2207433119.

References
1.
Pal I, Paltati C, Kaur C, Saini S, Kumar P, Jacob T . Morphological and neurochemical changes in GABAergic neurons of the aging human inferior colliculus. Hear Res. 2019; 377:318-329. DOI: 10.1016/j.heares.2019.02.005. View

2.
Fuentes-Santamaria V, Alvarado J, Brunso-Bechtold J, Henkel C . Upregulation of calretinin immunostaining in the ferret inferior colliculus after cochlear ablation. J Comp Neurol. 2003; 460(4):585-96. DOI: 10.1002/cne.10676. View

3.
Cai C, Liang X, Shi Y, Chu P, Pfaff S, Chen J . Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell. 2003; 5(6):877-89. PMC: 5578462. DOI: 10.1016/s1534-5807(03)00363-0. View

4.
DAngelo W, Sterbing S, Ostapoff E, Kuwada S . Role of GABAergic inhibition in the coding of interaural time differences of low-frequency sounds in the inferior colliculus. J Neurophysiol. 2005; 93(6):3390-400. DOI: 10.1152/jn.00956.2004. View

5.
Zhou X, Jen P, Seburn K, Frankel W, Zheng Q . Auditory brainstem responses in 10 inbred strains of mice. Brain Res. 2006; 1091(1):16-26. PMC: 2859191. DOI: 10.1016/j.brainres.2006.01.107. View