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A non-canonical pallidothalamic pathway for motor control

Chang, I. Y. M.; Paz, J. T.

2026-06-10 neuroscience
10.64898/2026.06.08.730902 bioRxiv
Show abstract

Coordinated movement relies on interactions between the basal ganglia and the thalamus, yet the circuits linking these structures are not fully understood. Here, we dissect a non-canonical basal ganglia output pathway, from the external globus pallidus (GPe) to the nucleus reticularis thalami (nRT). We show that GPe neurons synapse onto all nRT neurons with 100% connectivity. Strikingly, despite its GABAergic nature, GPe input excites the posterior nRT but inhibits the anterior nRT, due to region-specific expression of the chloride transporter KCC2. This divergence shapes downstream thalamocortical activity, producing feedforward inhibition in the somatosensory thalamus but not the motor thalamus. Functionally, the in vivo activity of GPe[->]nRT axons is time-locked to movement, and modulating the GPe[->]nRT pathway bidirectionally regulates movement in a state-dependent manner. Overall, our work highlights the GPe as a major regulator of thalamic activity and establishes a novel role of the GPe[->]nRT pathway in motor control. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/730902v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1d0bff2org.highwire.dtl.DTLVardef@1e9d8fcorg.highwire.dtl.DTLVardef@1a4a304org.highwire.dtl.DTLVardef@1ca7b3a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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