Objective: To test our hypothesis that a principal role of GPi GABAergic output is to regulate the dual burst and tonic modes of thalamocortical neurons. This would suggest the need to revise current basal ganglia direct-indirect pathway models.

Background: The classical basal ganglia model cannot account for the benefits of GPi pallidotomy and DBS on both hypo- and hyperkinetic features. Despite this conundrum, the mechanism by which GPi regulates thalamocortical drive has not been satisfactorily scrutinized. Brainstem GABAergic input induces hyperpolarization of thalamic membranes, which shifts thalamic neurons from a tonic towards a burst mode of firing. The relative roles of these two modes continue to be debated and have been largely disregarded for the motor system.

Methods: Neuronal discharge activity was recorded from pallidal-receiving VL thalamus in normal and dystonic rats (n = 27 normal and 22 dystonic neurons) and in motor cortex (MC) layer V (n = 7 normal and 10 dystonic neurons) at rest and additionally, with movement, along with EMGs.

Results: At rest, normal VL neurons showed a predominance of burst mode activity (70-75%). In contrast, the tonic mode predominated (75-80%) in dystonic rats, who showed 40% higher overall firing rates (p<0.05). In distinction, cerebellar-receiving VPL thalamic neurons were not altered in dystonic rats. With normal movement, VL neurons predominately maintained the burst mode, which was modulated beginning > 0.4 ms prior to onset of movement. In dystonic rats with movement, VL neurons largely switched to the burst mode, but neuronal firing only poorly followed EMG activity and ‘erroneously’ resembled burst activity of normal rats at rest. In MC, dystonic rats showed attenuated increments in spike counts prior to movement onset and an abnormal reduction in burstiness after the onset of movement.

Conclusions: Our findings suggest that normally GABAergic resting input from EP hyperpolarizes a majority of VL neurons and holds them chiefly in the baseline ‘ready’ burst mode. In dystonia, reduced GPi GABAergic resting output places VL neurons erroneously largely in the tonic mode with delayed and inaccurate switching to the desired burst mode. Lastly, we suggest that the burst mode should be the ideal mode for providing detailed motor-related signals to MC and in dystonia, the intra-burst discharge activity is highly abnormal.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/refined-basal-ganglia-model-accounting-for-gpi-modulation-of-thalamic-tonic-and-burst-modes/