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The immediate early gene Arc is not required for hippocampal long-term potentiation
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4202.full.pdf
Description
Published version
Size
2.3 MB
Format
Adobe PDF
Checksum (MD5)
3a36730deae8550700f23917508d5f2c
Author(s)
Kyrke-Smith, Madeleine
Volk, Lenora J
Cooke, Samuel F
Bear, Mark F
Huganir, Richard L
Shepherd, Jason D
Date Issued
2021
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Kyrke-Smith, Madeleine, Volk, Lenora J, Cooke, Samuel F, Bear, Mark F, Huganir, Richard L et al. 2021. "The immediate early gene Arc is not required for hippocampal long-term potentiation." Journal of Neuroscience, 41 (19).
Version
Final published version
Abstract
Memory consolidation is thought to occur through protein synthesis-dependent synaptic plasticity mechanisms such as long-term potentiation (LTP). Dynamic changes in gene expression and epigenetic modifications underlie the maintenance of LTP. Similar mechanisms may mediate the storage of memory. Key plasticity genes, such as the immediate early gene Arc, are induced by learning and by LTP induction. Mice that lack Arc have severe deficits in memory consolidation, and Arc has been implicated in numerous other forms of synaptic plasticity, including long-term depression and cell-to-cell signaling. Here, we take a comprehensive approach to determine if Arc is necessary for hippocampal LTP in male and female mice. Using a variety of Arc knock-out (KO) lines, we found that germline Arc KO mice show no deficits in CA1 LTP induced by high-frequency stimulation and enhanced LTP induced by theta-burst stimulation. Temporally restricting the removal of Arc to adult animals and spatially restricting it to the CA1 using Arc conditional KO mice did not have an effect on any form of LTP. Similarly, acute application of Arc antisense oligodeoxynucleotides had no effect on hippocampal CA1 LTP. Finally, the maintenance of in vivo LTP in the dentate gyrus of Arc KO mice was normal. We conclude that Arc is not necessary for hippocampal LTP and may mediate memory consolidation through alternative mechanisms.SIGNIFICANCE STATEMENT The immediate early gene Arc is critical for maintenance of long-term memory. How Arc mediates this process remains unclear, but it has been proposed to sustain Hebbian synaptic potentiation, which is a key component of memory encoding. This form of plasticity is modeled experimentally by induction of LTP, which increases Arc mRNA and protein expression. However, mechanistic data implicates Arc in the endocytosis of AMPA-type glutamate receptors and the weakening of synapses. Here, we took a comprehensive approach to determine if Arc is necessary for hippocampal LTP. We find that Arc is not required for LTP maintenance and may regulate memory storage through alternative mechanisms.
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1523/JNEUROSCI.0008-20.2021
