CELL-TYPE-SPECIFIC ALTERATIONS IN MEMBRANE AND SYNAPTIC PROPERTIES OF EXTERNAL GLOBUS PALLIDUS NEURONS IN PARKINSONIAN MICE

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta which leads to aberrant activity patterns in the basal ganglia (BG) circuitry. The external globus pallidus (GPe), a key BG nucleus, regulates motor function and integrates sensory information. Traditionally it is considered part of the indirect pathway and implicated in PD-related activity alterations. The GPe is primarily comprised of two neuronal subtypes: prototypic and arkypallidal cells, which exhibit distinct molecular markers, electrophysiological properties, synaptic connections, and developmental origins. Previous works have shown that GPe is involved in sensory processing, however, how this information processing changes following dopamine-depletion remains unknown. Here, we used in vivo whole-cell patch-clamp recordings in GPe neurons of anesthetized dopamine-intact and dopamine-depleted mice to address this question. Analysis of membrane properties of GPe cells revealed that in dopamine-depleted mice prototypic cells exhibit a decreased action potential (AP) firing frequency, reduced AP regularity, and hyperpolarized resting membrane potential compared to those of dopamine-intact mice. In contrast, no alterations in membrane properties are observed between the arkypallidal cells of the two groups. Additionally, while no differences are found in the response to whisker stimulation of prototypic cells between the two groups, arkypallidal cells of dopamine-depleted mice show a significant reduction in the amplitude of triphasic response compared to those from dopamine-intact mice. In conclusion, our results demonstrate that dopamine-depletion induces differential electrophysiological changes in GPe neurons that involve both alteration in membrane properties and synaptic inputs to the GPe cell populations.