Neuronal and astrocytic protein degradation are critical for fear memory formation

  1. Timothy J. Jarome1,2
  1. 1School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA
  2. 2School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA
  1. Corresponding author: tjjarome{at}vt.edu
  1. 3 These authors contributed equally to this work.

Abstract

Strong evidence has implicated proteasome-mediated protein degradation in the memory consolidation process. However, due to the use of pharmacological approaches, the cell type specificity of this remains unknown. Here, we used neuron-specific and novel astrocyte-specific CRISPR–dCas9–KRAB–MECP2 plasmids to inhibit protein degradation in a cell type-specific manner in the amygdala of male rats. We found that while inhibition of neuronal, but not astrocytic, protein degradation impaired performance during the training session, both resulted in impaired contextual fear memory retention. Together, these data provide the first evidence of a cell type-specific role for protein degradation in the memory consolidation process.

Footnotes

  • Received November 22, 2022.
  • Accepted February 21, 2023.

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