Cortex-Restricted Deletion of Foxp1 Impairs Visual Responses by Disrupting Geniculocortical Connections in a Mouse Model of Autism.

This animal study looked at why some autistic people have vision problems. Researchers studied mice with a gene change similar to what's found in some people with autism. These mice had trouble with depth perception (judging distances) and their brain's visual processing was weaker. The study found problems with brain connections and cell function that might explain vision difficulties in autism.

This preclinical study investigated visual deficits in autism using a mouse model with cortex-specific Foxp1 gene knockout. Researchers found that mice lacking cortical Foxp1 showed impaired depth perception and reduced visual signal processing in the primary visual cortex. The study revealed disrupted connections between the thalamus and visual cortex, along with structural changes in neurons and mitochondrial dysfunction. These findings suggest that FOXP1 mutations, a known autism risk factor, may contribute to visual problems in ASD through disrupted brain connectivity and cellular dysfunction.

The research provides mechanistic insights into autism-related visual impairments and suggests mitochondrial function as a potential therapeutic target.

Findings suggest FOXP1-related autism may involve specific visual processing deficits due to disrupted brain connectivity. Results point toward mitochondrial dysfunction as a potential therapeutic target. However, translation to human clinical applications requires further validation studies.

Animal model findings may not directly translate to humans. Sample size not reported. Single gene knockout may not represent the complexity of human autism. Visual assessments limited to specific measures and may not capture full range of visual differences in autism.

Visual deficits are prominent features of autism spectrum disorder (ASD), yet the underlying neural mechanisms remain unclear. Mutations in FOXP1, which is a major risk factor for ASD, are often associated with visual issues. This study aims to investigate how the loss of cortical Foxp1 may contribute to the visual problems. A mouse model of ASD was generated by specific knockout of Foxp1 in cortical progenitors and their descendant excitatory neurons (Foxp1-cKO).

We assessed visual depth perception using the visual cliff test. Visual signal conduction was evaluated through flash visual evoked potentials (FVEPs) and light-induced c-Fos neuronal activation in the primary visual cortex (V1). Geniculocortical afferents and connectivity were evaluated by immunolabeling of pre- and post-synaptic markers in V1. Dendrites and spines of layer IV neurons were analyzed using Golgi staining, and mitochondria were examined by Western blots and in neuronal cultures from V1.

Foxp1-cKO mice showed deficits in binocular depth perception. The knockout mice exhibited reduced FVEP amplitudes and diminished c-Fos activation in V1 neurons. Knocking out Foxp1 reduced geniculocortical connectivity and decreased dendrites and spines of layer IV neurons of V1. Deletion of Foxp1 impaired the mitochondria in the V1 cortex.

Foxp1-cKO mice have deficits in visual signal transmission and depth perception, indicating binocular vision abnormalities. This study highlights the importance of geniculocortical connectivity for binocular vision and offers new insights into the mechanisms underlying ASD-related visual impairments, suggesting future studies to explore therapies aimed at restoring mitochondrial function.