DYSFUNCTIONAL CORTICO-THALAMIC FEEDBACK CONNECTIVITY IN A MOUSE MODEL OF DEVELOPMENTAL DYSLEXIA

Developmental dyslexia is a neurodevelopmental disorder classically associated with alterations in language-related brain regions; however, converging evidence indicates that early sensory pathways are also affected, particularly those involved in visual and auditory temporal processing. Within the predictive coding framework, perception arises from the interaction between bottom-up sensory inputs and top-down predictions, with cortico-thalamic feedback pathways playing a key role in signaling mismatches between expected and incoming sensory signals. Human dyslexics have reduced connectivity within sensory pathways connecting first-order thalami with motion-sensitive auditory and visual areas. In addition, behavioral and functional neuroimaging studies indirectly suggest altered predictive feedback mechanisms in developmental dyslexia. Direct circuit-level evidence, however, is absent and impossible to obtain within human participants. Here, we developed a mouse model that mimics neurodevelopmental alterations relevant to dyslexia, focusing on impaired cortico-thalamic connectivity in the visual modality. To this end, we selectively manipulate layer 6 neurons of the rostrolateral visual cortex (VisRL), a higher-order motion-sensitive visual area. As expected, preliminary behavioral results showed intact discrimination of different temporal frequencies in this model, supporting preserved feedforward visual processing. We are now developing a behavioral paradigm to examine predictive processing of dynamic visual stimuli, in which repeated stimulus presentations establish expectations that are subsequently violated by subtle or salient changes in motion parameters. This ongoing work aims to determine whether dyslexia-related alterations preferentially impair feedback-based predictive processing rather than feedforward processing. Overall, this approach provides a framework to test how disrupted cortico-thalamic connectivity contributes to sensory processing difficulties associated with developmental dyslexia.