Input-specific control of interneuron numbers in nascent striatal networks

TY - JOUR

T1 - Input-specific control of interneuron numbers in nascent striatal networks

AU - Sreenivasan, Varun

AU - Serafeimidou-Pouliou, Eleni

AU - Exposito-Alonso, David

AU - Bercsenyi, Kinga

AU - Bernard, Clémence

AU - Bae, Sung Eun

AU - Oozeer, Fazal

AU - Hanusz-Godoy, Alicia

AU - Edwards, Robert H.

AU - Marín, Oscar

N1 - Funding Information: ACKNOWLEDGMENTS. We thank I. Andrew for excellent technical assistance; S. Anderson (University of Pennsylvania), K. Nave (Max Planck Institute for Experimental Medicine), and M. Verhage (Vrije Universiteit Amsterdam) for Nkx2-1-Cre, NexCre/+, and Stxbp1fl/fl mice, respectively; N. Dehorter and B. Rico for critical reading of the manuscript; and members of the O.M. and B. Rico laboratories for stimulating discussions and ideas. This work was supported by a grant from the European Research Council (ERC-2017-AdG 787355 to O.M.). Funding Information: We thank I. Andrew for excellent technical assistance; S. Anderson (University of Pennsylvania), K. Nave (Max Planck Institute for Experimental Medicine), and M. Verhage (Vrije Universiteit Amsterdam) for Nkx2-1-Cre, NexCre/+, and Stxbp1fl/fl mice, respectively; N. Dehorter and B. Rico for critical reading of the manuscript; and members of the O.M. and B. Rico laboratories for stimulating discussions and ideas. This work was supported by a grant from the European Research Council (ERC-2017-AdG 787355 to O.M.). Publisher Copyright: Copyright © 2022 the Author(s).

PY - 2022/5/17

Y1 - 2022/5/17

N2 - The assembly of functional neuronal circuits requires appropriate numbers of distinct classes of neurons, but the mechanisms through which their relative proportions are established remain poorly defined. Investigating the mouse striatum, we found that the two most prominent subtypes of striatal interneurons, parvalbumin-expressing (PV +) GABAergic and cholinergic (ChAT +) interneurons, undergo extensive programmed cell death between the first and second postnatal weeks. Remarkably, the survival of PV + and ChAT + interneurons is regulated by distinct mechanisms mediated by their specific afferent connectivity. While long-range cortical inputs control PV + interneuron survival, ChAT + interneuron survival is regulated by local input from the medium spiny neurons. Our results identify input-specific circuit mechanisms that operate during the period of programmed cell death to establish the final number of interneurons in nascent striatal networks.

AB - The assembly of functional neuronal circuits requires appropriate numbers of distinct classes of neurons, but the mechanisms through which their relative proportions are established remain poorly defined. Investigating the mouse striatum, we found that the two most prominent subtypes of striatal interneurons, parvalbumin-expressing (PV +) GABAergic and cholinergic (ChAT +) interneurons, undergo extensive programmed cell death between the first and second postnatal weeks. Remarkably, the survival of PV + and ChAT + interneurons is regulated by distinct mechanisms mediated by their specific afferent connectivity. While long-range cortical inputs control PV + interneuron survival, ChAT + interneuron survival is regulated by local input from the medium spiny neurons. Our results identify input-specific circuit mechanisms that operate during the period of programmed cell death to establish the final number of interneurons in nascent striatal networks.

KW - cell death

KW - cortex

KW - cortico-striatal projections

KW - interneurons

KW - striatum

UR - http://www.scopus.com/inward/record.url?scp=85129499696&partnerID=8YFLogxK

U2 - 10.1073/pnas.2118430119

DO - 10.1073/pnas.2118430119

M3 - Article

C2 - 35533272

AN - SCOPUS:85129499696

SN - 0027-8424

VL - 119

SP - e2118430119

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 20

M1 - e2118430119

ER -