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Independent computations within dendrites

Cortical pyramidal neurons typically have an elaborate dendritic tree that receives and integrates the many synaptic inputs targeting the neuron. An open question is how information is represented in dendrites in vivo. Otor et al. investigated synaptic computations in the apical tuft of layer 5 pyramidal neurons in the mouse motor cortex using two-photon calcium imaging, behavioral analysis, and cable modeling. Early-branching layer 5 pyramidal neurons showed marked compartmentalization of dendritic calcium signaling, whereas late-branching pyramidal neurons had synchronous tuft activation. N-methyl-d-aspartate spikes and cable properties could explain the varying compartmentalization patterns. Compartmentalized activity between hemi-trees was correlated with behavioral outcome. These results indicate a cell-type-dependent dynamic combinatorial code for motor representation. —PRS

Abstract

Tuft dendrites of layer 5 pyramidal neurons form specialized compartments important for motor learning and performance, yet their computational capabilities remain unclear. Structural-functional mapping of the tuft tree from the motor cortex during motor tasks revealed two morphologically distinct populations of layer 5 pyramidal tract neurons (PTNs) that exhibit specific tuft computational properties. Early bifurcating and large nexus PTNs showed marked tuft functional compartmentalization, representing different motor variable combinations within and between their two tuft hemi-trees. By contrast, late bifurcating and smaller nexus PTNs showed synchronous tuft activation. Dendritic structure and dynamic recruitment of the N-methyl-d-aspartate (NMDA)–spiking mechanism explained the differential compartmentalization patterns. Our findings support a morphologically dependent framework for motor computations, in which independent amplification units can be combinatorically recruited to represent different motor sequences within the same tree.

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References and Notes

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Published In

Science
Volume 376 | Issue 6590
15 April 2022

Submission history

Received: 7 November 2021
Accepted: 11 March 2022
Published in print: 15 April 2022

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Acknowledgments

We thank S. Marom and B. Engelhard for helpful comments on the manuscript. We also thank S. Schwartz for advice in statistical tests and S. Gafniel for movie editing.
Funding: This study was partially supported by the Israeli Science Foundation (J.S. and Y.S.), Prince funds (J.S. and Y.S.), Rappaport Foundation (J.S. and Y.S.), and Zuckerman Postdoctoral Fellowship (N.C.).
Author contributions: Designed research: J.S., N.C., Y.S. Performed experiments: Y.O., N.C., S.A., M.A. Analyzed data: S.A., Y.O., J.S., H.B., O.B., Y.S. Writing – original draft: J.S. Writing – review and editing: J.S., Y.O., S.A., A.P.-P., Y.S. Performed simulations: A.P.-P., S.A., J.S.
Competing interests: The authors declare that they have no competing interests.
Data and materials availability: All data are available in the manuscript or the supplementary materials. Computer code can be found in: https://github.com/SchillersLab/Dynamic-compartmental-computations-in-tuft-dendrites-.

Authors

Affiliations

Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, and Visualization.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, and Visualization.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing - original draft, and Writing - review & editing.
Yale University School of Medicine; Bethany, CT, USA.
Roles: Conceptualization, Formal analysis, Software, Visualization, and Writing - review & editing.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Investigation and Validation.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Methodology and Supervision.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Conceptualization, Formal analysis, and Writing - original draft.
Department of Physiology and Biophysics; University of Colorado School of Medicine, 12800 East 19th Avenue MS8307, Aurora, CO 8004, USA.
Roles: Conceptualization, Data curation, Formal analysis, Methodology, Software, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing.
Department of Physiology, Technion Medical School, Bat-Galim, Haifa 31096, Israel.
Roles: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, and Writing - review & editing.

Funding Information

Notes

*
Corresponding author. Email: [email protected] (J.S.); [email protected] (A.P.-P.)
These authors contributed equally to this work.

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