Cortical α-synuclein pathology induces neuronal hypoactivity andcircuit changes but not functional impairments in a model of early Lewy body dementia

Cortical α-synuclein pathology causes neuronal hypoactivity and circuit changes without impairing visuoperceptual function in a mouse model of early Lewy body dementia.

• Why it matters: Understanding how α-synuclein pathology affects cortical circuits is crucial for unraveling the mechanisms behind cognitive symptoms in Parkinson’s disease and Dementia with Lewy Bodies, especially since the link between pathology and functional impairment remains unclear.
• What they did: Researchers injected α-syn pre-formed fibrils into the visual cortex of mice and used longitudinal two-photon calcium imaging over six months to monitor neuronal activity and pathology, assessing visual responses and behavior.
• The result: While α-syn pathology reduced neuronal activity and altered local circuit responses, mice maintained visuoperceptual abilities, suggesting compensatory mechanisms that preserve function despite early cortical pathology.