Brainstem motor neuron dysmorphology and excitatory/inhibitory imbalance in an animal model of autism

Autism spectrum disorder is a neurodevelopmental disability that includes sensory disturbances. Hearing is frequently affected and ranges from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder. Valproic acid-exposed rats have fewer neurons in their auditory brainstem and thalamus, fewer calbindin-positive neurons, reduced ascending projections to the midbrain and thalamus, elevated thresholds, and delayed auditory brainstem responses. Additionally, in the auditory cortex, valproic acid exposure results in abnormal responses, decreased phase-locking, elevated thresholds, and abnormal tonotopic maps. We therefore hypothesized that in utero, valproic acid exposure would result in fewer neurons in auditory cortex, neuronal dysmorphology, fewer calbindin-positive neurons, and reduced connectivity. We approached this hypothesis using morphometric analyses, immunohistochemistry, and retrograde tract tracing. We found thinner cortical layers but no changes in the density of neurons, smaller pyramidal and non-pyramidal neurons in several regions, fewer neurons immunoreactive for calbindin-positive, and fewer cortical neurons projecting to the inferior colliculus. These results support the widespread impact of the auditory system in autism spectrum disorder and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening for autism spectrum disorder.

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Brainstem motor neuron dysmorphology and excitatory/inhibitory imbalance in an animal model of autism

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Folia Morphologica" are listed in PubMed.

Cited by 4 publications

References 33 publications

Abnormal vestibular brainstem structure and function in an animal model of autism spectrum disorder

Abnormal vestibular brainstem structure and function in an animal model of autism spectrum disorder

Abnormal auditory brainstem responses in an animal model of autism spectrum disorder

Cortical dysmorphology and reduced cortico-collicular projections in an animal model of autism spectrum disorder

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