The striatum is required for normal action selection, movement, and sensorimotor learning. Although action-specific striatal ensembles have been well documented, it is not well understood how these ensembles are formed and how their dynamics may evolve throughout motor learning. Here we used longitudinal 2-photon Ca imaging of dorsal striatal neurons in head-fixed mice as they learned to self-generate locomotion. We observed a significant activation of both direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs, respectively) during early locomotion bouts and sessions that gradually decreased over time. For dSPNs, onset- and offset-ensembles were gradually refined from active motion-nonspecific cells. iSPN ensembles emerged from neurons initially active during opponent actions before becoming onset- or offset-specific. Our results show that as striatal ensembles are progressively refined, the number of active nonspecific striatal neurons decrease and the overall efficiency of the striatum information encoding for learned actions increases.
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http://dx.doi.org/10.1101/2024.06.06.596654 | DOI Listing |
Neuron
January 2025
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Neuroscience, University of California, Berkeley, Berkeley, CA 94720, USA; Weill Neurohub, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated BioImaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:
Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood.
View Article and Find Full Text PDFElife
January 2025
Department of Neurology, University of Iowa, Iowa City, United States.
The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway.
View Article and Find Full Text PDFNat Commun
December 2024
Weldon School of Biomedical Engineering, West Lafayette, Indiana, IN, USA.
Circuit-based biomarkers distinguishing the gradual progression of Lewy pathology across synucleinopathies remain unknown. Here, we show that seeding of α-synuclein preformed fibrils in mouse dorsal striatum and motor cortex leads to distinct prodromal-phase cortical dysfunction across months. Our findings reveal that while both seeding sites had increased cortical pathology and hyperexcitability, distinct differences in electrophysiological and cellular ensemble patterns were crucial in distinguishing pathology spread between the two seeding sites.
View Article and Find Full Text PDFTrends Neurosci
January 2025
Université Libre de Bruxelles (ULB), ULB Neuroscience Institute, Neurophysiology Laboratory, Brussels, Belgium. Electronic address:
The dorsal striatum is instrumental in regulating motor control and goal-directed behaviors. The classical description of the two output pathways of the dorsal striatum highlights their antagonistic control over actions. However, recent experimental evidence implicates both pathways and their coordinated activities during actions.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
Locomotion is continuously regulated by an animal's position within an environment relative to goals. Direct and indirect pathway striatal output neurons (dSPNs and iSPNs) influence locomotion, but how their activity is naturally coordinated by changing environments is unknown. We found, in head-fixed mice, that the relative balance of dSPN and iSPN activity was dynamically modulated with respect to position within a visually-guided locomotor trajectory to retrieve reward.
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