Auditory processing and morphological anomalies in medial geniculate nucleus of Cntnap2 mutant mice.

Oct 27, 2015Behavioral neuroscience

Hearing processing and structural changes in the sound relay area of Cntnap2 mutant mice

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Abstract

Cntnap2 knockout mice displayed deficits in silent gap detection and enhanced pitch discrimination.

Atypical language development is a core symptom of autism spectrum disorder (ASD).
Mutation of the Cntnap2 gene is associated with auditory-processing abnormalities in mice.
Cntnap2 knockout mice demonstrated reduced performance in silent gap detection tasks.
These mutant mice outperformed controls in pitch-related discrimination tasks.
Stereological analysis indicated fewer neurons and smaller neuronal sizes in the medial geniculate nucleus of Cntnap2 knockout mice.
Findings suggest that CNTNAP2 plays a crucial role in the development and function of neural systems related to auditory processing.

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Genetic epidemiological studies support a role for CNTNAP2 in developmental language disorders such as autism spectrum disorder, specific language impairment, and dyslexia. Atypical language development and function represent a core symptom of autism spectrum disorder (ASD), with evidence suggesting that aberrant auditory processing-including impaired spectrotemporal processing and enhanced pitch perception-may both contribute to an anomalous language phenotype. Investigation of gene-brain-behavior relationships in social and repetitive ASD symptomatology have benefited from experimentation on the Cntnap2 knockout (KO) mouse. However, auditory-processing behavior and effects on neural structures within the central auditory pathway have not been assessed in this model. Thus, this study examined whether auditory-processing abnormalities were associated with mutation of the Cntnap2 gene in mice. Cntnap2 KO mice were assessed on auditory-processing tasks including silent gap detection, embedded tone detection, and pitch discrimination. Cntnap2 knockout mice showed deficits in silent gap detection but a surprising superiority in pitch-related discrimination as compared with controls. Stereological analysis revealed a reduction in the number and density of neurons, as well as a shift in neuronal size distribution toward smaller neurons, in the medial geniculate nucleus of mutant mice. These findings are consistent with a central role for CNTNAP2 in the ontogeny and function of neural systems subserving auditory processing and suggest that developmental disruption of these neural systems could contribute to the atypical language phenotype seen in autism spectrum disorder.

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Auditory processing and morphological anomalies in medial geniculate nucleus of Cntnap2 mutant mice.

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