Project description:The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Project description:The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
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.
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.