Sex- and etiology-specific effects on predictive processing in the inferior colliculus of two rat models of autism.

Scientists studied how the brains of male and female rats with autism-like traits process sounds differently. They used two different ways to create autism-like traits in rats and found that both males and females showed unusual brain responses to sounds, but in different ways depending on the cause of their autism-like traits. This helps explain why sensory processing differences vary so much between autistic individuals.

This study investigated auditory processing differences in two rat models of autism, examining sex-specific effects at the single-neuron level in the inferior colliculus. Using a genetic model (Grin2b deletion) and environmental model (prenatal valproic acid exposure), researchers recorded neuronal responses to auditory oddball paradigms. The study employed sophisticated statistical modeling to account for multiple variables including sex, brain region, and autism model type. Results revealed distinct alterations in predictive auditory processing that varied by sex and autism model, with different patterns across brain subdivisions.

The findings suggest that biological sex and underlying causes jointly influence early auditory computations in autism-like conditions.

Findings suggest sensory assessments should consider both sex and potential autism etiology. Results support developing targeted sensory interventions based on individual profiles. Research highlights importance of predictive coding frameworks for understanding autism sensory differences.

Animal model findings may not fully translate to humans. Sample size not reported, limiting generalizability. Single brain region focus may not capture broader sensory processing networks. Auditory paradigm may not reflect real-world sensory challenges.

Atypical sensory processing is a common feature of autism, yet the neural computations that give rise to these differences, particularly in relation to biological sex and etiological origin, remain unclear. Here we examine predictive auditory processing at the single-neuron level in the inferior colliculus of two adult rat models of autism: a genetic model with a heterozygous Grin2b deletion (Grin2b + /-) and an environmental model based on prenatal valproic acid exposure. We recorded neuronal responses to an auditory oddball paradigm and a cascade control sequence across lemniscal and non-lemniscal IC divisions under high-intensity stimulation, allowing us to derive indices of repetition suppression, prediction error and neuronal mismatch. Using generalized linear mixed-effects models that accounted for animal identity, inferior colliculus division, sex, and rat model, followed by hierarchical group-level comparisons, we identified robust alterations in predictive processing in both autism-like models.

These effects varied across inferior colliculus divisions and differed between sexes, revealing distinct phenotype-specific signatures. The results indicate that sex and etiology jointly modulate early auditory computations in autism. More broadly, our findings highlight the translational value of predictive coding frameworks and support the use of complementary animal models to capture neurobiological heterogeneity across the autism spectrum.