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Salient stimuli that modify behavior induce transcription of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and transport Arc mRNA into dendrites, suggesting that local Arc translation mediates synaptic plasticity that encodes such stimuli. Here, we demonstrate that long-term synaptic depression (LTD) in hippocampal neurons induced by group 1 metabotropic glutamate receptors (mGluRs) relies on rapid translation of Arc. mGluR-LTD induction causes long-term increases in AMPA receptor endocytosis rate and dendritic synthesis of Arc, a component of the AMPAR endocytosis machinery. Knockdown of Arc prevents mGluRs from triggering AMPAR endocytosis or LTD, and acute blockade of new Arc synthesis with antisense oligonucleotides blocks mGluR-LTD and AMPAR trafficking. In contrast, LTD induced by NMDA receptors does not persistently alter AMPAR endocytosis rate, induce Arc synthesis, or require Arc protein. These data demonstrate a role for local Arc synthesis specifically in mGluR-LTD and suggest that mGluR-LTD may be one consequence of Arc mRNA induction during experience.
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http://dx.doi.org/10.1016/j.neuron.2008.05.014 | DOI Listing |
Front Synaptic Neurosci
August 2025
Memory Research Laboratory, Brain Institute, UFRN, Natal, Brazil.
Non-reinforced reactivation destabilizes spatial memory in the Morris water maze (MWM), triggering reconsolidation, a protein synthesis-dependent process that restabilizes reactivated memories. PKMζ is a constitutively active, atypical PKC isoform implicated in memory storage. However, the potential involvement of this kinase in spatial memory reconsolidation remains unexplored.
View Article and Find Full Text PDFMol Neurobiol
July 2025
Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical Schools, University of São Paulo, Ribeirão Preto, SP, Brazil.
Afterdischarge (AD) is an experimental model of electrically induced seizures. When induced in limbic structures, AD is known to induce acute behavioral alterations and flattening of local field potentials that persist for a few minutes. However, impairments in more complex cognitive processes such as learning and memory can last for hours after the seizure.
View Article and Find Full Text PDFFront Pharmacol
May 2025
Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, United States.
The transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synaptic plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear.
View Article and Find Full Text PDFCell Rep
February 2025
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD
Hippocampal long-term potentiation (LTP) and long-term depression (LTD) are forms of synaptic plasticity, thought to be the molecular basis of learning and memory, dependent on dynamic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking. Alteration of endosomal pH negatively affects synaptic transmission and neural development, but it is unclear how pH is involved in AMPAR trafficking. We show that the proton-activated chloride (PAC) channel localizes to early and recycling endosomes in neurons and prevents endosome hyper-acidification.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, United States.
The transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4), also known as Proline-rich transmembrane protein 1 (PRRT1), is an AMPA-type glutamate receptor (AMPAR) auxiliary factor that is necessary for maintaining extra-synaptic pools of GluA1. Loss of SynDIG4, and the subsequent decrease in extra-synaptic GluA1, has been found to significantly impact synaptic plasticity in the hippocampus. However, how SynDIG4 establishes and maintains these pools is unclear.
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