Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

Autor: Diana Tothova, Zbynek Bures, Jiri Popelar, Tetyana Chumak, Iva Filova, Josef Syka, Gabriela Pavlinkova
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Inferior colliculus
sound processing
Gene Expression
Stimulation
auditory system
Calbindin
Glycine transporter
Mice
0302 clinical medicine
Hearing
Premovement neuronal activity
Biology (General)
Promoter Regions
Genetic
Spectroscopy
Neurons
Brain
General Medicine
inhibition
Computer Science Applications
Cell biology
Chemistry
030220 oncology & carcinogenesis
Auditory Perception
Female
Calretinin
QH301-705.5
LIM-Homeodomain Proteins
Mice
Transgenic
Biology
Article
Catalysis
inferior colliculus
Inorganic Chemistry
03 medical and health sciences
Evoked Potentials
Auditory
Brain Stem
otorhinolaryngologic diseases
Animals
Humans
Physical and Theoretical Chemistry
transcription factor ISL1
QD1-999
Molecular Biology
Olivocochlear system
PAX2 Transcription Factor
Organic Chemistry
Auditory Threshold
Inferior Colliculi
030104 developmental biology
nervous system
biology.protein
Parvalbumin
Transcription Factors
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 4507, p 4507 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 9
ISSN: 1422-0067
DOI: 10.3390/ijms22094507
Popis: 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 (Tg) expressing Isl1 under the Pax2 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 Tg mice. In this study, we investigated how Isl1 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 Tg 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 Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.
Databáze: OpenAIRE
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