INTRINSIC PROPERTIES OF EXTERNAL GLOBUS PALLIDUS NEURONS IN DOPAMINE DEPLETED MICE

Parkinson´s disease (PD) is a neurodegenerative disorder associated with the loss of midbrain dopaminergic neurons in the substantia nigra pars compacta and their projections in the basal ganglia (BG). The globus pallidus externa (GPe) is a central part of the BG that is affected by dopamine loss. It is composed of two subpopulations that differ in terms of electrophysiological properties, molecular markers, and targets. The majority of GPe cells are called prototypic neurons, which are highly active, while the arkypallidal neurons are a smaller group of less active cells projecting to the striatum. In this study, we characterized the intrinsic properties and intrapallidal connectivity of the subpopulations and their alteration in the unilateral 6-hydroxydopamine model of PD in mice using the ex-vivo slice preparation. We found that both types of neurons showed reduced excitability following dopamine depletion. Specifically, we report that the prototypic cells of dopamine-depleted mice display reduced input resistance and increased rheobase compared to dopamine-intact animals. Arkypallidal cells in dopamine depleted mice showed decreased membrane potential and increased rheobase, as well as decreased action potential amplitude and half-width compared to controls. Recording the membrane properties of GPe cells in the presence of synaptic transmission blockers revealed that changes in excitability may be partially attributed to changes in synaptic input strength. Our results thus point towards a combined effect of intrinsic and synaptic mechanisms underlying the reduced excitability in the GPe neurons in a cell-type-specific manner following dopamine depletion. Deciphering these mechanisms could enable better treatment for PD.