title: Metabotropic Glutamate Receptors Induce a Form of LTP Controlled by Translation and Arc Signaling in the Hippocampus.
abstract: Activity-dependent bidirectional modifications of excitatory synaptic strength are essential for learning and storage on new memories. Research on bidirectional synaptic plasticity has largely focused on long-term potentiation (LTP) and long-term depression (LTD) mechanisms that rely on the activation of NMDA receptors. In principle, metabotropic glutamate receptors (mGluRs) are also suitable to convert synaptic activity into intracellular signals for synaptic modification. Indeed, dysfunction of a form of LTD that depends on Type I mGluRs (mGluR-LTD), but not NMDARs, has been implicated in learning deficits in aging and mouse models of several neurological conditions, including Fragile X syndrome and Alzheimer's disease. To determine whether mGluR activation can also induce LTP in the absence of NMDAR activation, we examined in hippocampal slices from rats and mice, an NMDAR-independent form of LTP previously characterized as dependent on voltage-gated Ca(2+) channels. We found that this form of LTP requires activation of Type I mGluRs and, like mGluR-LTD but unlike NMDAR-dependent plasticity, depends crucially on protein synthesis controlled by fragile X mental retardation protein and on Arc signaling. Based on these observations, we propose the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs.
  
  
  CONCLUSIONS
  Bidirectional changes of synaptic strength are crucial for the encoding of new memories. Currently, the only activity-dependent mechanism known to support such bidirectional changes are long-term potentiation (LTP) and long-term depression (LTD) forms that relay on the activation of NMDA receptors. Metabotropic glutamate receptors (mGluRs) are, in principle, also suitable to trigger bidirectional synaptic modifications. However, only the mGluR-dependent form of LTD has been characterized. Here we report that an NMDAR-independent form of LTP, initially characterized as dependent on voltage-gated Ca(2+) channels, also requires the activation of mGluRs. These finding suggest the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs.
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218.
authors: Hui
authors: H
authors: Wang
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de Valparaiso, Chile.
authors: Alvaro O
authors: AO
authors: Ardiles
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218.
authors: Sunggu
authors: S
authors: Yang
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218.
authors: Trinh
authors: T
authors: Tran
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218.
authors: Rafael
authors: R
authors: Posada-Duque
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de Valparaiso, Chile.
authors: Gonzalo
authors: G
authors: Valdivia
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218.
authors: Min
authors: M
authors: Baek
authors: BCMB-Neuroscience Johns Hopkins Medical School, Baltimore, Maryland 21205.
authors: Yang-An
authors: YA
authors: Chuang
authors: Centro Interdisciplinario de Neurociencia de Valparaiso, Universidad de Valparaiso, Chile.
authors: Adrian G
authors: http://orcid.org/0000-0003-1532-7527
authors: AG
authors: Palacios
authors: BCMB-Neuroscience Johns Hopkins Medical School, Baltimore, Maryland 21205.
authors: Michela
authors: http://orcid.org/0000-0002-9585-6500
authors: M
authors: Gallagher
authors: Department of Brain and Psychological Sciences, Johns Hopkins University, Baltimore, Maryland 21218, and.
authors: Paul
authors: P
authors: Worley
authors: Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, Department of Brain and Psychological Sciences, Johns Hopkins University, Baltimore, Maryland 21218, and kirkwood@jhu.edu.
authors: Alfredo
authors: http://orcid.org/0000-0001-9148-9742
authors: A
authors: Kirkwood
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018094:Receptors, Metabotropic Glutamate; C092069:activity regulated cytoskeletal-associated protein
keywords: arc; bidirectional; metabotropic glutamate receptors; protein synthesis; synaptic plasticity; translation