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Comparative effects of inactivation and dopamine receptor agents in the dorsolateral and dorsomedial striatum on performance of action sequences in rats

Turner, K. M.; Svegborn, A.; Robbins, T. W.

2026-01-22 neuroscience
10.64898/2026.01.22.701165 bioRxiv
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RationaleRecent research on habits and skills has produced a wave of new theories regarding the shift in control from medial to lateral regions of the dorsal striatum, and how these regions are implicated in the selected and executed of action sequences. ObjectivesTo examine the comparative effects of muscimol/baclofen inactivation and dopamine D1 and D2 receptor agents in the dorsomedial (DMS) and dorsolateral (DLS) striatum on the performance of skilled action sequences. MethodsInfusions were made in well-trained rats using the five-step nose poke task to isolate the effects on initiation, execution and termination components of skilled action sequences. ResultsDLS inactivation produced sequencing deficits like those observed with pre-training lesions, indicating that the DLS is critical for both the acquisition and performance of sequences. Behaviour was unchanged following DMS inactivation, consistent with models of DMS disengagement following training. Infusions of D1 and D2 antagonists did not alter behaviour, however the D2 receptor agonist quinpirole increased sequence errors at a low dose and reduced sequences at the high dose in the DLS. DLS manipulations impaired sequence initiation and termination as well as reward transitions, while the chunking ballistic response pattern was largely unaltered, indicating that between-but not within-sequence actions rely on the DLS. ConclusionsSkilled action sequencing, including chunk transitions was dependent on DLS and its modulation by D2 receptors, but not on DMS function. Using a novel sequencing task, these results support the dissociable and dopamine-dependent role of the dorsal striatum subregions in performing skilled motor actions.

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