Disruption of Ascending and Descending Visual Processing Circuits

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopamine-carrying neurons in the substantia nigra in the brain. Non-motor symptoms (particularly visual impairment) significantly impair patients' quality of life, but the primary pathogenesis is poorly understood. This study aims to investigate the mechanisms by which the brain uses structural changes in the enzyme leucine-rich ribonuclease 2 (LRRK2) to process visual information, with a particular focus on abnormalities in top-down brain control and bottom-up sensory pathways. The results show that the LRRK2-G2019S mutation causes excessive LRRK2 expression in brain regions that affect higher-level visual processing, such as attention and working memory, while simultaneously inhibiting dopamine activity in the nucleus accumbens and viscerocortical sensory feedback, leading to impaired visual processing and impaired integration of visual information in two-dimensional space. This results in visual problems ranging from blurred and reduced vision to unusual dreams. This ongoing study uses LRRK2-G2019S mutant fruit flies, which will allow us to identify and investigate causal relationships from LRRK2 molecular pathology to visual network abnormalities and behavioral disorders. This study provides a new rationale for screening and identifying possible early signs (e.g., vision changes, abnormal eye movement patterns, and changes in body functions), so that early intervention in PD may be possible before the disease has spread throughout the body.