Neuronal substrates of a division of labor in the external globus pallidus

Orateur : Peter MAGILL (University of Oxford)

Classical schemes of the functional organization of basal ganglia circuits are founded on two key principles : (1) Neurons of the external globus pallidus (GPe) are relatively homogeneous in form and function ; and (2) information flows from striatum to GPe, but not vice versa. In this lecture, I will highlight how recent studies of GPe cells and circuits in dopamine-intact and dopamine-depleted brains challenge both of these tenets. It is now clear that the distinct temporal activities of two populations of GPe neuron in vivo are underpinned by their distinct developmental origins, molecular architecture and axonal connectivities. Thus, a first population of “prototypic” GPe neu-rons express the transcription factors Nkx2-1 and Lhx6, fire action potentials at relatively high rates and in anti-phase to striatal projection neurons, and mainly target downstream basal ganglia nuclei. In contrast, a second population of “arkypallidal” neurons express the transcription factor FoxP2, fire at low rates and in-phase with striatal projection neurons, and only innervate striatum. Prototyp-ic and arkypallidal neurons also disparately encode spontaneous movements. Computational models predict that the divergent firing rates/patterns of prototypic and arkypallidal neurons in vivo arise from their distinct intrinsic membrane properties and different inputs from striatal and other neu-rons ; some predictions have already been validated by studies in vitro. In conclusion, two types of GPe neuron are well suited to perform a division of labor when orchestrating activity in the basal ganglia.

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