Subregion-specific rules govern the distribution of neuronal immediate-early gene induction

Ben Jerry Gonzales, Diptendu Mukherjee, Reut Ashwal-Fluss, Yonatan Loewenstein, Ami Citri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The induction of immediate-early gene (IEG) expression in brain nuclei in response to an experience is necessary for the formation of long-term memories. Additionally, the rapid dynamics of IEG induction and decay motivates the common use of IEG expression as markers for identification of neuronal assemblies ("ensembles") encoding recent experience. However, major gaps remain in understanding the rules governing the distribution of IEGs within neuronal assemblies. Thus, the extent of correlation between coexpressed IEGs, the cell specificity of IEG expression, and the spatial distribution of IEG expression have not been comprehensively studied. To address these gaps, we utilized quantitative multiplexed single-molecule fluorescence in situ hybridization (smFISH) and measured the expression of IEGs (Arc, Egr2, and Nr4a1) within spiny projection neurons (SPNs) in the dorsal striatum of mice following acute exposure to cocaine. Exploring the relevance of our observations to other brain structures and stimuli, we also analyzed data from a study of single-cell RNA sequencing of mouse cortical neurons. We found that while IEG expression is graded, the expression of multiple IEGs is tightly correlated at the level of individual neurons. Interestingly, we observed that region-specific rules govern the induction of IEGs in SPN subtypes within striatal subdomains. We further observed that IEG-expressing assemblies form spatially defined clusters within which the extent of IEG expression correlates with cluster size. Together, our results suggest the existence of IEG-expressing neuronal "superensembles," which are associated in spatial clusters and characterized by coherent and robust expression of multiple IEGs.

Original languageAmerican English
Pages (from-to)23304-23310
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number38
DOIs
StatePublished - 22 Sep 2020

Bibliographical note

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Keywords

  • Cell assemblies
  • Experience
  • Immediate-early genes
  • Inducible transcription
  • Neurons

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