Session 3E: Striatal Input to the External Globus Pallidus in Parkinson’s Disease

Convincing evidence indicates that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of movement disorders such as Parkinson’s disease. The GPe’s activity is regulated by other basal ganglia structures, including the dorsal striatum (dStr), which forms the principal inhibitory input to the GPe. Despite the clinical importance of the GPe in motor disorders, there is limited information about the characteristics and functional impact of this key innervation into the GPe by the dStr’s spiny projection neurons (SPNs). It is unknown how dStr input from direct pathway SPNs (dSPNs) compares to that from the indirect pathway SPNs (iSPNs). Furthermore, according to the classic basal ganglia circuitry model, it is expected that dopamine depletion in Parkinson\u27s disease (simulated with the addition of 6-OHDA) increases iSPN-GPe input, which may contribute to the hypokinetic symptoms of Parkinson’s. Using cell-specific transgenic mice, optical stimulation of striatopallidal axons and terminals within the GPe, and subsequent analysis of stimulation-evoked quantal events, the electrophysiological characteristics of dStr-GPe input was better understood in this study. This work revises our understanding of the striatopallidal pathway and provides the foundation for future studies of the GPe’s function and dysfunction