Early uneven ear input induces long-lasting differences in left-right motor function

Authors

Michelle W. Antoine, Albert Einstein College of Medicine, Bronx, New YorkFollow
Xiaoxia Zhu, University of South Florida
Marianne Dieterich, Ludwig-Maximilians University MunichFollow
Thomas Brandt, Ludwig-Maximilians University MunichFollow
Sarath Vijayakumar, University of Nebraska-LincolnFollow
Nicholas McKeehan, Albert Einstein College of Medicine, Bronx, New York
Joseph C. Arezzo, Albert Einstein College of Medicine, Bronx, New York
R. Suzanne Zukin, Albert Einstein College of Medicine, Bronx, New York
David A. Borkholder, Rochester Institute of TechnologyFollow
Sherri M. Jones, University of Nebraska-LincolnFollow
Robert D. Frisina, University of South FloridaFollow
Jean M. Hébert, Albert Einstein College of Medicine, Bronx, New YorkFollow

Document Type

Article

Citation

Antoine MW, Zhu X, Dieterich M, Brandt T, Vijayakumar S, McKeehan N, et al. (2018) Early uneven ear input induces long-lasting differences in left±right motor function. PLoS Biol 16(3): e2002988. https://doi.org/10.1371/journal.pbio.2002988

Comments

Copyright: © 2018 Antoine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License

Abstract

How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission. By unilaterally targeting striatal activity with an antagonist of extracellular signal-regulated kinase (ERK), a downstream integrator of striatal neurotransmitter signaling, we can reverse or exaggerate rotational preference in these mice. By surgically biasing vestibular failure to one ear, we can dictate the direction of motor preference, illustrating the influence of uneven vestibular failure in establishing the outward asymmetries in motor preference. The inner ear±induced striatal asymmetries identified here intersect with non±ear-induced asymmetries previously linked to lateralized motor behavior across species and suggest that aspects of left±right brain function in mammals can be ontogenetically influenced by inner ear input. Consistent with inner ear input contributing to motor asymmetry, we also show that, in humans with normal ear function, the motor-dominant hemisphere, measured as handedness, is ipsilateral to the ear with weaker vestibular input.

Despite a long-standing fascination with asymmetries in left±right brain function, very little is known about the causes of functional brain asymmetry in mammals, which appear independent of the mechanisms that create anatomical asymmetries during development. Asymmetries in motor function are a common example and include preferred turning direction, handedness, and footedness. In this study, using mouse models, we establish a causal link between transient imbalances in degenerating inner ear function and the establishment of stable asymmetries in neural pathways that regulate motor activity and in motor behavior. Our study also suggests that shared mechanisms may underlie lateralized motor behaviors across mammalian species. For example, we show that in humans with normal ear function, the strength of the vestibular response from each ear in the forebrain correlates with asymmetric motor behavior, measured as handedness. In a broader sense, our study reveals a conceptually novel role for sensory input in shaping the asymmetric distribution of brain function, a process for which there is otherwise no clear mechanism.