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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 |
Cell Rep
September 2025
Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; The Phil & Penny Knight In
The dorsal striatum plays a critical role in action selection, movement, and sensorimotor learning. While action-specific striatal ensembles have been described, the mechanisms underlying their formation and evolution during motor learning remain poorly understood. Here, we employed longitudinal two-photon Ca imaging of dorsal striatal neurons in head-fixed mice as they learned to self-initiate locomotion.
View Article and Find Full Text PDFAdv Sci (Weinh)
July 2025
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao, Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Ba
Cortical traveling waves coordinate communication among distributed neural ensembles to modulate brain function and dysfunction through distinct spatiotemporal propagation patterns. However, the brain-wide propagation dynamics of traveling waves from different origins and their roles in regulating behavior remain unclear. Using optogenetics alongside whole-brain fMRI in mice, it is demonstrated that optogenetic activation of the medial prefrontal cortex and primary somatosensory area induces cortical spreading depression (CSD)-like traveling waves.
View Article and Find Full Text PDFSci Adv
July 2025
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The basolateral amygdala (BLA) assigns valence to sensory stimuli, with a dedicated nociceptive ensemble encoding the negative valence of pain. However, the effects of chronic pain on the transcriptomic signatures and projection architecture of this BLA nociceptive ensemble are not well understood. Here, we show that optogenetic inhibition of the nociceptive BLA ensemble reduces affective-motivational behaviors in chronic neuropathic pain.
View Article and Find Full Text PDFStriatal spiny-projection neurons (SPNs) integrate glutamatergic inputs from the motor cortex and thalamus with neuromodulatory signals to regulate motor output. Ca imaging has demonstrated that spatially overlapping ensembles of direct and indirect pathway SPNs (dSPNs, iSPNs) are co-active during spontaneous movement. This co-activity is statistically greater among nearby neurons, correlates with behavioral state, and changes in an SPN-type-specific manner under pathological conditions.
View Article and Find Full Text PDFCell Rep
July 2025
Champalimaud Research, Champalimaud Foundation, 1400-038 Lisbon, Portugal; Zuckerman Mind Brain Behavior Institute, Department of Neuroscience, Columbia University, New York, NY 10027, USA; Allen Institute, Seattle, WA 98109, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Net
L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson's disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link between SPN activity patterns and specific dyskinetic movements remains unknown. To explore this, we implemented a data-driven method for clustering movements based on high-resolution motion sensors and video recordings.
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