Experience-Induced Arc/Arg3.1 Primes CA1 Pyramidal Neurons for Metabotropic Glutamate Receptor-Dependent Long-Term Synaptic Depression

• Published in: Neuron (Cambridge, Mass.) Vol. 80; no. 1; pp. 72 - 79
• Main Authors: Jakkamsetti, Vikram, Tsai, Nien-Pei, Gross, Christina, Molinaro, Gemma, Collins, Katie A., Nicoletti, Ferdinando, Wang, Kuan H., Osten, Pavel, Bassell, Gary J., Gibson, Jay R., Huber, Kimberly M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-10-2013; Elsevier Limited
• Subjects: Animals; Artificial chromosomes; Autism; Cognition & reasoning; Cytoskeletal Proteins - metabolism; Dendrites - metabolism; Genes, Reporter - genetics; Hippocampus - physiology; Learning - physiology; Long-Term Synaptic Depression - physiology; Mice; Nerve Tissue Proteins - metabolism; Neuronal Plasticity - radiation effects; Neurons; Neurons - metabolism; Proteins; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - metabolism; Synaptic Transmission - physiology; Transcriptional Activation - genetics; Transcriptional Activation - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.07.020

A novel experience induces the Arc/Arg3.1 gene as well as plasticity of CA1 neural networks. To understand how these are linked, we briefly exposed GFP reporter mice of Arc transcription to a novel environment. Excitatory synaptic function of CA1 neurons with recent in vivo Arc induction (ArcGFP+) was similar to neighboring noninduced neurons. However, in response to group 1 metabotropic glutamate receptor (mGluR) activation, ArcGFP+ neurons preferentially displayed long-term synaptic depression (mGluR-LTD) and robust increases in dendritic Arc protein. mGluR-LTD in ArcGFP+ neurons required rapid protein synthesis and Arc, suggesting that dendritic translation of Arc underlies the priming of mGluR-LTD. In support of this idea, novelty exposure increased Arc messenger RNA in CA1 dendrites and promoted mGluR-induced translation of Arc in hippocampal synaptoneurosomes. Repeated experience suppressed synaptic transmission onto ArcGFP+ neurons and occluded mGluR-LTD ex vivo. mGluR-LTD priming in neurons with similar Arc activation history may contribute to encoding a novel environment.
•mGluR activation induces LTD only in CA1 neurons with recent in vivo Arc induction•mGluRs stimulate dendritic Arc protein in CA1 neurons with recent Arc induction•Novelty increases dendritic Arc mRNA, mGluR-induced synaptic Arc synthesis, and LTD•Repeated experience induces mGluR-LTD onto Arc-positive CA1 neurons in vivo
The consequence of experience-induced Arc gene on synaptic function is unknown. Jakkamsetti et al. find that novelty-induced Arc primes CA1 neurons for mGluR-dependent long-term synaptic depression through rapid translation of dendritic Arc mRNA, which may contribute to encoding of a salient experience.