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A pivotal role of GSK-3 in synaptic plasticity
Bradley, Clarrisa A.,Peineau, Sté,phane,Taghibiglou, Changiz,Nicolas, Celine S.,Whitcomb, Daniel J.,Bortolotto, Zuner A.,Kaang, Bong-Kiun,Cho, Kwangwook,Wang, Yu Tian,Collingridge, Graham L. Frontiers Media S.A. 2012 Frontiers in molecular neuroscience Vol.5 No.-
<P>Glycogen synthase kinase-3 (GSK-3) has many cellular functions. Recent evidence suggests that it plays a key role in certain types of synaptic plasticity, in particular a form of long-term depression (LTD) that is induced by the synaptic activation of N-methyl-D-aspartate receptors (NMDARs). In the present article we summarize what is currently known concerning the roles of GSK-3 in synaptic plasticity at both glutamatergic and GABAergic synapses. We summarize its role in cognition and speculate on how alterations in the synaptic functioning of GSK-3 may be a major factor in certain neurodegenerative disorders.</P>
Long-term depression in the CNS
Collingridge, Graham L.,Peineau, Stephane,Howland, John G.,Wang, Yu Tian Nature Publishing Group, a division of Macmillan P 2010 Nature reviews. Neuroscience Vol.11 No.7
<P>Long-term depression (LTD) in the CNS has been the subject of intense investigation as a process that may be involved in learning and memory and in various pathological conditions. Several mechanistically distinct forms of this type of synaptic plasticity have been identified and their molecular mechanisms are starting to be unravelled. Most studies have focused on forms of LTD that are triggered by synaptic activation of either NMDARs (N-methyl-d-aspartate receptors) or metabotropic glutamate receptors (mGluRs). Converging evidence supports a crucial role of LTD in some types of learning and memory and in situations in which cognitive demands require a flexible response. In addition, LTD may underlie the cognitive effects of acute stress, the addictive potential of some drugs of abuse and the elimination of synapses in neurodegenerative diseases.</P>
The JAK/STAT Pathway Is Involved in Synaptic Plasticity
Nicolas, Cé,line ,S.,Peineau, Sté,phane,Amici, Mascia,Csaba, Zsolt,Fafouri, Assia,Javalet, Charlotte,Collett, Valerie ,J.,Hildebrandt, Lars,Seaton, Gillian,Choi, Sun-Lim,Sim, Su-Eo Cell Press 2012 Neuron Vol.73 No.2
<▼1><P><B>Summary</B></P><P>The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is involved in many cellular processes, including cell growth and differentiation, immune functions and cancer. It is activated by various cytokines, growth factors, and protein tyrosine kinases (PTKs) and regulates the transcription of many genes. Of the four JAK isoforms and seven STAT isoforms known, JAK2 and STAT3 are highly expressed in the brain where they are present in the postsynaptic density (PSD). Here, we demonstrate a new neuronal function for the JAK/STAT pathway. Using a variety of complementary approaches, we show that the JAK/STAT pathway plays an essential role in the induction of NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus. Therefore, in addition to established roles in cytokine signaling, the JAK/STAT pathway is involved in synaptic plasticity in the brain.</P></▼1><▼2><P>The authors demonstrate a new neuronal function for the JAK/STAT pathway in the induction of NMDA-receptor-dependent long-term depression (NMDAR-LTD) in the hippocampus.</P></▼2>
Affaticati, P,Mignen, O,Jambou, F,Potier, M-C,Klingel-Schmitt, I,Degrouard, J,Peineau, S,Gouadon, E,Collingridge, G L,Liblau, R,Capiod, T,Cohen-Kaminsky, S Macmillan Publishers Limited 2011 CELL DEATH AND DIFFERENTIATION Vol.18 No.1
L-glutamate, the major excitatory neurotransmitter, also has a role in non-neuronal tissues and modulates immune responses. Whether NMDA receptor (NMDAR) signalling is involved in T-cell development is unknown. In this study, we show that mouse thymocytes expressed an array of glutamate receptors, including NMDARs subunits. Sustained calcium (Ca<SUP>2+</SUP>) signals and caspase-3 activation in thymocytes were induced by interaction with antigen-pulsed dendritic cells (DCs) and were inhibited by NMDAR antagonists MK801 and memantine. NMDARs were transiently activated, triggered the sustained Ca<SUP>2+</SUP> signal and were corecruited with the PDZ-domain adaptor postsynaptic density (PSD)-95 to thymocyte-DC contact zones. Although T-cell receptor (TCR) activation was sufficient for relocalization of NMDAR and PSD-95 at the contact zone, NMDAR could be activated only in a synaptic context. In these T-DC contacts, thymocyte activation occurred in the absence of exogenous glutamate, indicating that DCs could be a physiological source of glutamate. DCs expressed glutamate, glutamate-specific vesicular glutamate transporters and were capable of fast glutamate release through a Ca<SUP>2+</SUP>-dependent mechanism. We suggest that glutamate released by DCs could elicit focal responses through NMDAR-signalling in T cells undergoing apoptosis. Thus, synapses between T and DCs could provide a functional platform for coupling TCR activation and NMDAR signalling, which might reflect on T-cell development and modulation of the immune response.