The fluid, seemingly effortless execution of sequences of movements is a ubiquitous feature of everyday motor skills. Ample evidence for their importance comes from the common human neuropathologies (Parkinson's disease, in particular) in which sequential skills are especially impaired. Long-term motor sequencing skills are formed, most likely, across multiple time scales in associative, premotor, and motor circuits of the brain. Recent evidence suggests that for each of these brain circuits, a sub-cortical loop through the basal ganglia (BG) contributes selectively to reinforcement-driven modulation of thalamo-cortical plasticity. These findings lead to the hypothesis that BG loops play central roles in the acquisition of sequence information, but are less important in the recall or use of already-learned sequences.
The specific aims (SAs) of this proposal will test that general hypothesis by using non-human primates: 1) to determine if neurons in the globus pallidus interna (GPi, the primary BG output nucleus for skeletomotor function) preferentially encode sequence information during new learning;and 2) to test whether intact BG circuits are necessary for new sequence learning. Associative loops through the BG may play a greater role in the fast acquisition of flexible goal-directed representations of sequence information while the premotor and motor loops may mediate slow acquisition of habit-like effector-specific representations. We will infer the circuit membership of individual GPi neurons by stimulating different cortical areas and observing the orthodromic inhibitory effects. Animals will perform a discrete sequence production task using novel, familiar and over-trained sequences. SAl will test if neuronal encoding of sequence-specific information in associative, premotor, and motor circuits of GPi reflects the predicted roles of these circuits in learning novel, familiar, and over-trained sequences. SA2 will determine if an interruption of BG output (i.e., GPi inactivation or lesion) selectively impairs training-related improvements in sequence performance. The prediction is that inactivations or lesions in the associative BG circuit will impair novel sequence learning whereas lesions in premotor and motor circuits will block the further refinement and solidification of performance of already-familiar sequences. Results from these experiments will aid in understanding the physiological basis for

Public Health Relevance

TThe proposed work is central to the problem of understanding the mechansims where practice leads to to reorganization of the human motor system in the face of aging, neurodeneration, stroke or brain injury. Understanding these mechansims has an impact on the design of therapies directed at preserving function, developing compensator movements and ultimately, developing novel motor capacity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Santa Barbara
Santa Barbara
United States
Zip Code
Crossley, Matthew J; Horvitz, Jon C; Balsam, Peter D et al. (2016) Expanding the role of striatal cholinergic interneurons and the midbrain dopamine system in appetitive instrumental conditioning. J Neurophysiol 115:240-54
Ramkumar, Pavan; Acuna, Daniel E; Berniker, Max et al. (2016) Chunking as the result of an efficiency computation trade-off. Nat Commun 7:12176
Ohbayashi, Machiko; Picard, Nathalie; Strick, Peter L (2016) Inactivation of the Dorsal Premotor Area Disrupts Internally Generated, But Not Visually Guided, Sequential Movements. J Neurosci 36:1971-6
Smith, J David; Zakrzewski, Alexandria C; Johnston, Jennifer J R et al. (2015) Generalization of category knowledge and dimensional categorization in humans (Homo sapiens) and nonhuman primates (Macaca mulatta). J Exp Psychol Anim Learn Cogn 41:322-35
Glaser, Joshua I; Zamft, Bradley M; Church, George M et al. (2015) Puzzle Imaging: Using Large-Scale Dimensionality Reduction Algorithms for Localization. PLoS One 10:e0131593
Pasquereau, Benjamin; Turner, Robert S (2015) Dopamine neurons encode errors in predicting movement trigger occurrence. J Neurophysiol 113:1110-23
Bassett, Danielle S; Yang, Muzhi; Wymbs, Nicholas F et al. (2015) Learning-induced autonomy of sensorimotor systems. Nat Neurosci 18:744-51
Overduin, Simon A; d'Avella, Andrea; Roh, Jinsook et al. (2015) Representation of Muscle Synergies in the Primate Brain. J Neurosci 35:12615-24
Acuna, Daniel E; Berniker, Max; Fernandes, Hugo L et al. (2015) Using psychophysics to ask if the brain samples or maximizes. J Vis 15:
Cieslak, Matthew; Ingham, Roger J; Ingham, Janis C et al. (2015) Anomalous white matter morphology in adults who stutter. J Speech Lang Hear Res 58:268-77

Showing the most recent 10 out of 110 publications