Striosomes Mediate Value-Based Learning Vulnerable in Age and a Huntington’s Disease Model
| Autor: | Sebastien Delcasso, Dan Hu, Emily Hueske, Sabrina M. Drammis, Qingyang Zhang, Charu Ramakrishnan, Leif G. Gibb, Joshua K. Xiong, Karl Deisseroth, Cody A. Siciliano, Lara I. Rakocevic, Alexander Friedman, Tomoko Yoshida, Sebastian E. Toro Arana, Erik D. Nelson, Jiajia Zhao, Hope Lutwak, Thomas J. Diefenbach, Kaden S. DiMarco, Ann M. Graybiel, Raimundo X. Rodriguez, Cody W. Carter |
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| Rok vydání: | 2020 |
| Předmět: |
Aging
Striosome Models Neurological education Action Potentials Value (computer science) Mice Transgenic Striatum Biology Article General Biochemistry Genetics and Molecular Biology Discrimination Learning Photometry 03 medical and health sciences 0302 clinical medicine Calcium imaging Reward Huntington's disease Interneurons Task Performance and Analysis medicine Animals Learning Discrimination learning 030304 developmental biology 0303 health sciences Behavior Animal Compartment (ship) Task engagement medicine.disease Corpus Striatum Disease Models Animal Huntington Disease Parvalbumins Nerve Net Neuroscience Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | PMC Cell |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2020.09.060 |
| Popis: | Learning valence-based responses to favorable and unfavorable options requires judgments of the relative value of the options, a process necessary for species survival. We have found, using engineered mice, that circuit connectivity and function of the striosome compartment of the striatum are critical for this type of learning. Calcium imaging during valence-based learning exhibited a selective correlation between learning and striosomal, but not matrix, signals. This striosomal activity encoded discrimination learning and was correlated with task engagement, which could, in turn, be regulated by chemogenetic excitation and inhibition. Striosomal function during discrimination learning was disturbed with aging, and severely so in a mouse model of Huntington’s disease. Anatomical and functional connectivity of parvalbumin-positive, putative fast-spiking interneurons (FSIs) to striatal projection neurons was enhanced in striosomes compared to matrix in mice that learned. Computational modeling of these findings suggests that FSIs can modulate striosomal signal-to-noise ratio, crucial for discrimination and learning. |
| Databáze: | OpenAIRE |
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