In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice

Amit Agarwal, Payam Dibaj, Celia M. Kassmann, Sandra Goebbels, Klaus Armin Nave, Markus H. Schwab

Research output: Contribution to journalArticle

Abstract

To study the function of individual neurons that are embedded in a complex neural network is difficult in mice. Conditional mutagenesis permits the spatiotemporal control of gene expression including the ablation of cells by toxins. To direct expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2) selectively to cortical neurons, we replaced the coding region of the murine Nex1 gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When injected with tamoxifen, adult NEX-CreERT2 mice induced reporter gene expression exclusively in projection neurons of the neocortex and hippocampus. By titrating the tamoxifen dosage, we achieved recombination in single cells, which allowed multiphoton imaging of neocortical neurons in live mice. When hippocampal projection neurons were genetically ablated by induced expression of diphteria toxin, within 20 days the inflammatory response included the infiltration of CD3+ T cells. This marks a striking difference from similar studies, in which dying oligodendrocytes failed to recruit cells of the adaptive immune system.

Original languageEnglish (US)
Pages (from-to)1473-1486
Number of pages14
JournalCerebral Cortex
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2012

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Keywords

  • Cre knock-in
  • connectivity
  • hippocampus
  • pyramidal cells
  • tamoxifen

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Agarwal, A., Dibaj, P., Kassmann, C. M., Goebbels, S., Nave, K. A., & Schwab, M. H. (2012). In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice. Cerebral Cortex, 22(7), 1473-1486. https://doi.org/10.1093/cercor/bhr214