Active intermixing of indirect and direct neurons builds the striatal mosaic

AbstractThe striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such mosaic ensures the balanced activity of the two pathways, how it emerges remains largely unknown. Here, we show that both SPN populations are specified embryonically and progressively intermix through multidirectional iSPN migration. Using conditional mutants of the dSPN-specific transcription factor Ebf1, we found that inactivating this gene impaired selective dSPN properties, including axon pathfinding, whereas molecular and functional features of iSPN were preserved. Remarkably, Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, revealing that intermixing is a parallel process to compartment formation. Our study reveals that, while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture.

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Modular organization of projection neurons in the matrix compartment of the primate striatum

Journal of Neuroscience ◽

10.1523/jneurosci.11-03-00779.1991 ◽

1991 ◽

Vol 11 (3) ◽

pp. 779-791 ◽

Cited By ~ 50

Author(s):

JM Gimenez-Amaya ◽

AM Graybiel

Keyword(s):

Modular Organization ◽

Projection Neurons ◽

The Matrix ◽

Matrix Compartment

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Differential organization of cortical inputs to striatal projection neurons of the matrix compartment in rats

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2015.00051 ◽

2015 ◽

Vol 9 ◽

Cited By ~ 23

Author(s):

Yunping Deng ◽

Jose Lanciego ◽

Lydia Kerkerian-Le Goff ◽

Patrice Coulon ◽

Pascal Salin ◽

...

Keyword(s):

Projection Neurons ◽

Striatal Projection Neurons ◽

The Matrix ◽

Matrix Compartment ◽

Cortical Inputs

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Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2008013117 ◽

2020 ◽

Vol 117 (40) ◽

pp. 25074-25084 ◽

Cited By ~ 3

Author(s):

Whitney E. Heavner ◽

Shaoyi Ji ◽

James H. Notwell ◽

Ethan S. Dyer ◽

Alex M. Tseng ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Single Cell ◽

Progenitor Cells ◽

Cell Fate ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Projection Neurons ◽

Cortical Projection ◽

Functional Features

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types of mature cortical projection neurons defined by their distinct gene-expression profiles. Moreover, exactly how and when neurons diversify their function during development is unknown. Here we relate gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversify neuron cell fate. We compare these gene-expression profiles with published profiles of single cells isolated from similar populations and establish that layer-defined cell classes encompass cell subtypes and developmental trajectories identified using single-cell sequencing. Given the depth of our sequencing, we identify groups of transcription factors with particularly dense subclass-specific regulation and subclass-enriched transcription factor binding motifs. We also describe transcription factor-adjacent long noncoding RNAs that define each subclass and validate the function of Myt1l in balancing the ratio of the two subclasses in vitro. Our multidimensional approach supports an evolving model of progressive restriction of cell fate competence through inherited transcriptional identities.

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Complete representation of action space and value in all striatal pathways

10.1101/2020.03.29.983825 ◽

2020 ◽

Cited By ~ 2

Author(s):

Moritz Weglage ◽

Emil Wärnberg ◽

Iakovos Lazaridis ◽

Ourania Tzortzi ◽

Konstantinos Meletis

Keyword(s):

Large Scale ◽

Dorsal Striatum ◽

Action Space ◽

Projection Neurons ◽

Indirect Pathway ◽

Complete Representation ◽

Decision Variables ◽

The Matrix ◽

Action Value ◽

Dorsomedial Striatum

ABSTRACTThe dorsal striatum plays a central role in motor and decision programs, such as the selection and execution of particular actions and the evaluation of their outcomes. A standard model has emerged where distinct output pathways encode separate motor-action signals, including selection-evaluation division in the matrix versus patch compartments. We used large-scale cell-type specific calcium imaging during motor and decision behaviors to determine and contrast the activity of individual striatal projection neurons (SPNs) belonging to one of the three major output pathways in the dorsomedial striatum – patch Oprm1+ SPNs versus the D1+ direct and A2A+ indirect pathway. We found that Oprm1+ SPNs were tuned to a number of different behavioral categories, such as to different movements, or to discrete actions and decisions in a two-choice task, and these complex representations were found to the same extent in all three striatal output pathways. The sharp tuning of individual SPNs was highly stereotyped over time while performing a specific task, but the tuning profile remapped between different behavioral contexts. In addition to action representations, SPNs showed pathway-independent representation of decision-variables such as the trial strategy and the action value. We propose that all three major output pathways in the dorsomedial striatum share a similarly complete representation of the entire action space, including task- and phase-specific signals of action value and choice.

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