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Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics
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 i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499544/ https://www.ncbi.nlm.nih.gov/pubmed/36095210 http://dx.doi.org/10.1073/pnas.2123373119 |
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author | Lituma, Pablo J. Singer, Robert H. Das, Sulagna Castillo, Pablo E. |
author_facet | Lituma, Pablo J. Singer, Robert H. Das, Sulagna Castillo, Pablo E. |
author_sort | Lituma, Pablo J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9499544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-94995442023-03-12 Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics Lituma, Pablo J. Singer, Robert H. Das, Sulagna Castillo, Pablo E. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2022-09-12 2022-09-20 /pmc/articles/PMC9499544/ /pubmed/36095210 http://dx.doi.org/10.1073/pnas.2123373119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Lituma, Pablo J. Singer, Robert H. Das, Sulagna Castillo, Pablo E. Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title | Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title_full | Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title_fullStr | Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title_full_unstemmed | Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title_short | Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
title_sort | real-time imaging of arc/arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499544/ https://www.ncbi.nlm.nih.gov/pubmed/36095210 http://dx.doi.org/10.1073/pnas.2123373119 |
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