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.

• Keywords
• auditory system, inferior colliculus, inhibition, sound processing, transcription factor ISL1,
• MeSH
• Inferior Colliculi metabolism   physiology   MeSH
• Gene Expression genetics   MeSH
• Humans MeSH
• Brain physiology   MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Neurons physiology   MeSH
• Promoter Regions, Genetic genetics   MeSH
• LIM-Homeodomain Proteins genetics   metabolism   MeSH
• Hearing MeSH
• Auditory Perception genetics   physiology   MeSH
• Evoked Potentials, Auditory, Brain Stem physiology   MeSH
• Auditory Threshold physiology   MeSH
• PAX2 Transcription Factor genetics   MeSH
• Transcription Factors genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• insulin gene enhancer binding protein Isl-1 MeSH Browser
• PAX2 protein, human MeSH Browser
• Pax2 protein, mouse MeSH Browser
• LIM-Homeodomain Proteins MeSH
• PAX2 Transcription Factor MeSH
• Transcription Factors MeSH