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

Throughout life, sensory systems adapt to the sensory environment to provide optimal responses to relevant tasks. In the case of a developing system, sensory inputs induce changes that are permanent and detectable up to adulthood. Previously, we have shown that rearing rat pups in a complex acoustic environment (spectrally and temporally modulated sound) from postnatal day 14 (P14) to P28 permanently improves the response characteristics of neurons in the inferior colliculus and auditory cortex, influencing tonotopical arrangement, response thresholds and strength, and frequency selectivity, along with stochasticity and the reproducibility of neuronal spiking patterns. In this study, we used a set of behavioral tests based on a recording of the acoustic startle response (ASR) and its prepulse inhibition (PPI), with the aim to extend the evidence of the persistent beneficial effects of the developmental acoustical enrichment. The enriched animals were generally not more sensitive to startling sounds, and also, their PPI of ASR, induced by noise or pure tone pulses, was comparable to the controls. They did, however, exhibit a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of a background tone or by a silent gap in background noise. The differences in the PPI of ASR between the enriched and control animals were significant at lower (55 dB SPL), but not at higher (65-75 dB SPL), intensities of background sound. Thus, rearing pups in the acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under more difficult testing conditions, i.e., with a worsened stimulus clarity. We confirmed, using behavioral tests, that an acoustically enriched environment during the critical period of development influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood.

• MeSH
• Acoustic Stimulation methods   MeSH
• Critical Period, Psychological * MeSH
• Rats MeSH
• Animals, Newborn MeSH
• Rats, Long-Evans MeSH
• Pitch Discrimination physiology   MeSH
• Auditory Perception physiology   MeSH
• Evoked Potentials, Auditory, Brain Stem physiology   MeSH
• Reflex, Startle physiology   MeSH
• Age Factors MeSH
• Environment * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

It is well known that auditory experience during early development shapes response properties of auditory cortex (AC) neurons, influencing, for example, tonotopical arrangement, response thresholds and strength, or frequency selectivity. Here, we show that rearing rat pups in a complex acoustically enriched environment leads to an increased reliability of responses of AC neurons, affecting both the rate and the temporal codes. For a repetitive stimulus, the neurons exhibit a lower spike count variance, indicating a more stable rate coding. At the level of individual spikes, the discharge patterns of individual neurons show a higher degree of similarity across stimulus repetitions. Furthermore, the neurons follow more precisely the temporal course of the stimulus, as manifested by improved phase-locking to temporally modulated sounds. The changes are persistent and present up to adulthood. The results document that besides basic alterations of receptive fields presented in our previous study, the acoustic environment during the critical period of postnatal development also leads to a decreased stochasticity and a higher reproducibility of neuronal spiking patterns.

• MeSH
• Action Potentials * MeSH
• Acoustic Stimulation * MeSH
• Neurons physiology   MeSH
• Rats, Long-Evans MeSH
• Auditory Perception physiology   MeSH
• Auditory Cortex physiology   MeSH
• Environment MeSH
• Animals MeSH
• Sound MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH