Researchers Identify Non-Canonical Brain Pathway Linking Basal Ganglia to Thalamus in Motor Control
Researchers have characterized a previously underappreciated neural circuit running from the external globus pallidus (GPe) to the nucleus reticularis thalami (nRT) that plays a direct role in regulating movement. The pathway is notable because the same inhibitory (GABAergic) signal paradoxically excites some nRT neurons while inhibiting others, depending on regional expression of the chloride transporter KCC2. This finding expands understanding of how the basal ganglia influence thalamocortical activity and could have implications for movement disorders.
A new study posted to bioRxiv describes a non-canonical output pathway from the external globus pallidus (GPe) to the nucleus reticularis thalami (nRT), two structures involved in motor control. The researchers found that GPe neurons synapse onto all nRT neurons with 100% connectivity, making it a highly pervasive circuit. Unusually, the GPe's GABAergic (inhibitory) input produces opposite effects in different nRT subregions: excitation in the posterior nRT and inhibition in the anterior nRT, a divergence explained by region-specific expression of the chloride cotransporter KCC2, which governs how neurons respond to inhibitory neurotransmitters. This differential signaling in turn shapes downstream thalamocortical activity, generating feedforward inhibition in the somatosensory thalamus but not the motor thalamus. In live animals, GPe axons projecting to the nRT fire in a time-locked manner relative to movement, and experimentally manipulating this pathway bidirectionally altered movement in a state-dependent way. The findings position the GPe as a major regulator of thalamic activity beyond its canonical output routes and open new avenues for understanding basal ganglia dysfunction in conditions such as Parkinson's disease.
What's missing
As a preprint, this study has not yet undergone formal peer review, so its methods and conclusions have not been independently validated. The study does not address whether the KCC2-dependent excitation/inhibition divergence is conserved across species beyond the animal model used, nor does it directly test the pathway's relevance to human movement disorders.
What different sources said
- bioRxivCenter
A non-canonical pallidothalamic pathway for motor control
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