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Arc expression regulates long-term potentiation magnitude and metaplasticity in area CA1 of the hippocampus in ArcKR mice.
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  • maisy Haley ,
  • Jeanri Bertrand ,
  • Vanessa Torrico Anderson ,
  • Mukattar Fuad ,
  • Bruno Frenguelli,
  • Sonia Correa,
  • Mark Wall
maisy Haley
University of Warwick
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Jeanri Bertrand
University of Warwick
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Vanessa Torrico Anderson
University of Warwick
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Mukattar Fuad
University of Warwick
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Bruno Frenguelli
University of Warwick
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Sonia Correa
Manchester Metropolitan University
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Mark Wall
University of Warwick

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Expression of the immediate early gene Arc/Arg3.1 (Arc), a key mediator of synaptic plasticity, is enhanced by neural activity and then reduced by proteasome-dependent degradation. We have previously shown that disruption of Arc degradation, in an Arc knock-in mouse (ArcKR), where the predominant Arc ubiquitination sites were mutated, reduced the threshold to induce, and also enhanced, the strength of Group I metabotropic glutamate receptor-mediated long-term depression (DHPG-LTD). Here we have investigated if ArcKR expression changes long-term potentiation (LTP) in CA1 area of the hippocampus. As previously reported, there was no change in basal synaptic transmission at Schaffer collateral/commissural-CA1 (SC-CA1) synapses in ArcKR versus wild-type (WT) mice. There was however a significant increase in the amplitude of synaptically-induced (with low frequency paired-pulse stimulation) LTD in ArcKR mice. Theta burst stimulation-evoked LTP at SC-CA1 synapses was significantly reduced in ArcKR versus WT mice (after 2 hours). Group 1 mGluR priming of LTP was abolished in ArckR mice, which could also potentially contribute to a depression of LTP. Although high frequency-stimulation (HFS)-induced LTP was not significantly different in ArcKR compared to WT mice (after 1 hour) there was a phenotype in environmentally enriched mice, with the ratio of LTP to short-term potentiation (STP) significantly reduced in ArcKR mice. These findings support the hypothesis that Arc ubiquitination supports the induction and expression of LTP, likely via limiting Arc-dependent removal of AMPA receptors at synapses.
20 Jun 2023Submitted to European Journal of Neuroscience
21 Jun 2023Submission Checks Completed
21 Jun 2023Assigned to Editor
21 Jun 2023Review(s) Completed, Editorial Evaluation Pending
10 Jul 2023Reviewer(s) Assigned
18 Aug 2023Editorial Decision: Revise Major
18 Sep 20231st Revision Received
18 Sep 2023Review(s) Completed, Editorial Evaluation Pending
18 Sep 2023Submission Checks Completed
18 Sep 2023Assigned to Editor
18 Sep 2023Reviewer(s) Assigned
27 Sep 2023Editorial Decision: Accept