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The External Globus Pallidus is a Major Basal Ganglia Output Hub with Action-Specific Circuits [Gpe 10X]

ABSTRACT: The indirect basal ganglia pathway is classically viewed as suppressing movement via the external globus pallidus (GPe), which has largely been regarded as an inhibitory relay nucleus. Using whole-brain projection mapping, single-neuron reconstruction, transcriptomics, rabies tracing, and closed-loop optogenetics, we show that the GPe is itself a major modular output structure, organized into parallel channels that selectively control distinct actions. Projection-defined GPe populations directly target thalamic and brainstem motor centers and exhibit action-specific dynamics and functions. GPe→PPN neurons are selectively suppressed during locomotion, and their manipulation bidirectionally controls locomotion. Critically, D2-SPN activation promotes locomotion through disinhibition of this pathway, revealing a direct movement-facilitating route stemming from D2-SPNs. In contrast, GPe→Pf neurons selectively regulate forelimb action sequences. These findings establish the GPe as a modular basal ganglia output structure and substantially revise canonical models of direct/indirect pathway function.

ORGANISM(S): Mus musculus

PROVIDER: GSE345248 | GEO | 2026/08/31

REPOSITORIES: GEO

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The External Globus Pallidus is a Major Basal Ganglia Output Hub with Action-Specific Circuits [SMART-seq]

Project description:The indirect basal ganglia pathway is classically viewed as suppressing movement via the external globus pallidus (GPe), which has largely been regarded as an inhibitory relay nucleus. Using whole-brain projection mapping, single-neuron reconstruction, transcriptomics, rabies tracing, and closed-loop optogenetics, we show that the GPe is itself a major modular output structure, organized into parallel channels that selectively control distinct actions. Projection-defined GPe populations directly target thalamic and brainstem motor centers and exhibit action-specific dynamics and functions. GPe→PPN neurons are selectively suppressed during locomotion, and their manipulation bidirectionally controls locomotion. Critically, D2-SPN activation promotes locomotion through disinhibition of this pathway, revealing a direct movement-facilitating route stemming from D2-SPNs. In contrast, GPe→Pf neurons selectively regulate forelimb action sequences. These findings establish the GPe as a modular basal ganglia output structure and substantially revise canonical models of direct/indirect pathway function.

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