Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for

Benjamin Kopecky; Rhonda Decook; Bernd Fritzsch

doi:10.1037/a0026896

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Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for

Journal article

Peer reviewed

Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for

Benjamin Kopecky, Rhonda Decook and Bernd Fritzsch

Behavioral neuroscience, Vol.126(2), pp.301-313

04/2012

DOI: 10.1037/a0026896

PMCID: PMC3314111

PMID: 22309445

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Abstract

Due to the multisensory input into the balance system, the loss of one input, such as an ear, can generally be compensated for. However, when a mismatch or incomplete loss of inputs occurs, the ability to compensate for the stimulus misrepresentation may be compromised. The inner ear and cerebellum are important input and processing centers for balance but no genetic models have been generated to assess balance or compensation in the abnormal development of both these organs/brain areas. Important to their formation is regulation of proliferation mediated by the proto-oncogene N-Myc. Conditional knockouts (CKOs) of N-Myc using Tg(Pax2-Cre) have a misshapen and smaller ear with a fused utricle, saccule, and cochlea and absent horizontal canal, aberrant cochlear and vestibular innervations, and a size reduction in the cerebellum. CKOs are viable with obvious behavioral deficits, including circling behavior and unstable gait. To test the degree of ataxia and possible compensation of vestibular defects in these mutant mice, we use the Noldus Catwalk System to assess the gait of Tg(Pax2-Cre) N-Myc CKOs over five months. N-Myc CKOs perform worse than control littermates, in particular, in step regularity. We show that disrupting one member of the Myc family during embryonic development coincides with a differential loss of function in the cochlea compared to the vestibular apparatus. In addition, we show that the distortion in the ear morphology combined with a reduction of the cerebellum, rather than a complete loss of the vestibular-cerebellar pathway, leads to partial behavioral compensation that remains unchanged over time.

Cochlea - embryology

Gait

Cochlea - physiopathology

Gait Ataxia - physiopathology

Vestibule, Labyrinth - physiopathology

Gait Ataxia - embryology

Cerebellum - physiopathology

Genes, myc

Cerebellum - abnormalities

Mice, Knockout

Cerebellum - embryology

Animals

Vestibule, Labyrinth - embryology

Mice

Vestibular Diseases - physiopathology

Cochlea - abnormalities

Vestibular Diseases - genetics

Vestibular Diseases - embryology

Details

Title: Subtitle: Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for
Creators: Benjamin Kopecky - Department of Biology and Carver College of Medicine, Medical Scientist Training Program, University of Iowa, USA. benjamin-kopecky@uiowa.edu
Rhonda Decook
Bernd Fritzsch
Resource Type: Journal article
Publication Details: Behavioral neuroscience, Vol.126(2), pp.301-313
DOI: 10.1037/a0026896
PMID: 22309445
PMCID: PMC3314111
NLM abbreviation: Behav Neurosci
ISSN: 0735-7044
eISSN: 1939-0084
Publisher: United States
Grant note: R01 DC005590 / NIDCD NIH HHS R01 DC005590-01 / NIDCD NIH HHS P30 DC010362 / NIDCD NIH HHS R01-DC055095590 / NIDCD NIH HHS DC010362 / NIDCD NIH HHS UL1 RR024979 / NCRR NIH HHS UL1 RR024979-01 / NCRR NIH HHS
Language: English
Date published: 04/2012
Academic Unit: Statistics and Actuarial Science; Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9983985964102771

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