High-throughput morphometric and transcriptomic profiling uncovers composition of naïve and sensory-deprived cortical cholinergic VIP/CHAT neurons

Nadav Yayon, Oren Amsalem, Tamara Zorbaz, Or Yakov, Serafima Dubnov, Katarzyna Winek, Amir Dudai, Gil Adam, Anna K. Schmidtner, Marc Tessier-Lavigne, Nicolas Renier, Naomi Habib, Idan Segev, Michael London, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cortical neuronal networks control cognitive output, but their composition and modulation remain elusive. Here, we studied the morphological and transcriptional diversity of cortical cholinergic VIP/ChAT interneurons (VChIs), a sparse population with a largely unknown function. We focused on VChIs from the whole barrel cortex and developed a high-throughput automated reconstruction framework, termed PopRec, to characterize hundreds of VChIs from each mouse in an unbiased manner, while preserving 3D cortical coordinates in multiple cleared mouse brains, accumulating thousands of cells. We identified two fundamentally distinct morphological types of VChIs, bipolar and multipolar that differ in their cortical distribution and general morphological features. Following mild unilateral whisker deprivation on postnatal day seven, we found after three weeks both ipsi- and contralateral dendritic arborization differences and modified cortical depth and distribution patterns in the barrel fields alone. To seek the transcriptomic drivers, we developed NuNeX, a method for isolating nuclei from fixed tissues, to explore sorted VChIs. This highlighted differentially expressed neuronal structural transcripts, altered exitatory innervation pathways and established Elmo1 as a key regulator of morphology following deprivation.

Original languageAmerican English
Article numbere110565
JournalEMBO Journal
Volume42
Issue number1
DOIs
StatePublished - 4 Jan 2023

Bibliographical note

Funding Information:
The authors would like to dedicate this manuscript to the memory of Ms Lili Safra, whose generous support of our Brain center enabled this work and many others. We are also grateful to Dr Sebastian Lobentanzer, Frankfurt, and Shani Vaknine, Jerusalem for advice and assistance in RNA‐seq analysis; and to Drs Yoseph Addadi, Rehovot, and Ester R Bennett, David S Greenberg, Sagiv Shifman, Yael Kalisman and Ron Refaeli, Jerusalem for their contributions toward this study. We acknowledge the support of this study by the European Research Council Advanced Award 321501 and the Israel Science Foundation Grant no. 1016/18 (to HS), and a joint Edmond and Lily Safra Center of Brain Sciences (ELSC) grant (to ML and HS) as well as the Gatsby charitable foundation, by the Drahi family foundation (to IS). KW and TZ were supported by postdoctoral ELSC fellowships (KW was a Shimon Peres Fellow at the ELSC), NY, OA, and AD were supported by predoctoral ELSC fellowships, and GA received a summer ELSC fellowship.

Funding Information:
The authors would like to dedicate this manuscript to the memory of Ms Lili Safra, whose generous support of our Brain center enabled this work and many others. We are also grateful to Dr Sebastian Lobentanzer, Frankfurt, and Shani Vaknine, Jerusalem for advice and assistance in RNA-seq analysis; and to Drs Yoseph Addadi, Rehovot, and Ester R Bennett, David S Greenberg, Sagiv Shifman, Yael Kalisman and Ron Refaeli, Jerusalem for their contributions toward this study. We acknowledge the support of this study by the European Research Council Advanced Award 321501 and the Israel Science Foundation Grant no. 1016/18 (to HS), and a joint Edmond and Lily Safra Center of Brain Sciences (ELSC) grant (to ML and HS) as well as the Gatsby charitable foundation, by the Drahi family foundation (to IS). KW and TZ were supported by postdoctoral ELSC fellowships (KW was a Shimon Peres Fellow at the ELSC), NY, OA, and AD were supported by predoctoral ELSC fellowships, and GA received a summer ELSC fellowship.

Publisher Copyright:
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Keywords

  • 3D
  • ChAT
  • deprivation
  • interneurons
  • reconstruction

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