Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics. Academic Article uri icon

Overview

abstract

  • The ability of neurons to process and store salient environmental features underlies information processing in the brain. Long-term information storage requires synaptic plasticity and regulation of gene expression. While distinct patterns of activity have been linked to synaptic plasticity, their impact on immediate early gene (IEG) expression remains poorly understood. The activity regulated cytoskeleton associated (Arc) gene has received wide attention as an IEG critical for long-term synaptic plasticity and memory. Yet, to date, the transcriptional dynamics of Arc in response to compartment and input-specific activity is unclear. By developing a knock-in mouse to fluorescently tag Arc alleles, we studied real-time transcription dynamics after stimulation of dentate granule cells (GCs) in acute hippocampal slices. To our surprise, we found that Arc transcription displayed distinct temporal kinetics depending on the activation of excitatory inputs that convey functionally distinct information, i.e., medial and lateral perforant paths (MPP and LPP, respectively). Moreover, the transcriptional dynamics of Arc after synaptic stimulation was similar to direct activation of GCs, although the contribution of ionotropic glutamate receptors, L-type voltage-gated calcium channel, and the endoplasmic reticulum (ER) differed. Specifically, we observed an ER-mediated synapse-to-nucleus signal that supported elevations in nuclear calcium and, thereby, rapid induction of Arc transcription following MPP stimulation. By delving into the complex excitation-transcription coupling for Arc, our findings highlight how different synaptic inputs may encode information by modulating transcription dynamics of an IEG linked to learning and memory.

publication date

  • September 12, 2022

Research

keywords

  • Cytoskeletal Proteins
  • Genes, Immediate-Early
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC9499544

Scopus Document Identifier

  • 85137660380

Digital Object Identifier (DOI)

  • 10.1073/pnas.2123373119

PubMed ID

  • 36095210

Additional Document Info

volume

  • 119

issue

  • 38