LTP Inhibits LTD in the Hippocampus via Regulation of GSK3β

@article{Peineau2007LTPIL,
  title={LTP Inhibits LTD in the Hippocampus via Regulation of GSK3$\beta$},
  author={Stephane Peineau and Changiz Taghibiglou and Clarrisa Bradley and Tak Pan Wong and Lidong Liu and Jie Lu and Edmond Lo and Dongchuan Wu and Emilia Saule and Tristan Bouschet and Paul Matthews and John T R Isaac and Zuner Assis Bortolotto and Yu Tian Wang and Graham L. Collingridge},
  journal={Neuron},
  year={2007},
  volume={53},
  pages={703-717}
}
Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3beta inhibitors block the induction of LTD. Furthermore, the activity of… Expand
Synaptic plasticity: Balancing LTP and LTD
  • K. Whalley
  • Chemistry
  • Nature Reviews Neuroscience
  • 2007
10.1038/nrn2123 Two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) are cellular processes involved in learning and memory. Although they produceExpand
GSK-3β regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα
TLDR
The data suggest that GSK-3β phosphorylates PI4KIIα to stabilize the expression of synaptic NMDA receptors, and this kinase is strongly implicated in the induction of NMDA receptor-dependent long-term depression. Expand
GSK3α, not GSK3β, drives hippocampal NMDAR‐dependent LTD via tau‐mediated spine anchoring
TLDR
This work targets the GSK3 isoforms with shRNA knock‐down in mouse hippocampus and with novel isoform‐selective drugs to dissect their roles in LTD, and finds that GSK 3α, but not G SK3β, is required for LTD. Expand
GSK3β Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels.
TLDR
It is shown that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3β knockdown in layer 2/3 of the mouse somatosensory cortex. Expand
Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments
TLDR
It is concluded that upregulation of GSK-3 impairs the synaptic plasticity both functionally and structurally, which may underlie the Gsk-3-involved memory deficits. Expand
GSK‐3β regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα
TLDR
Data suggest that GSK‐3β phosphorylates PI4KIIα to stabilize NMDA receptors at the synapse to regulate the surface expression of AMPA receptors. Expand
PTEN counteracts PIP3 upregulation in spines during NMDA-receptor-dependent long-term depression
TLDR
FRET imaging is used to monitor changes in PIP3 levels in dendritic spines from CA1 hippocampal neurons under basal conditions and upon induction of NMDA receptor (NMDAR)-dependent LTD and LTP and finds that PIP 3 undergoes constant turnover in dendsite turnover. Expand
GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
TLDR
It is found that mice with GSK-3β deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior, and data suggest that G SK-3 β in hippocampal DG excited neurons is essential for maintaining synaptic plasticity and memory. Expand
Dynamic range of GSK3α not GSK3β is essential for bidirectional synaptic plasticity at hippocampal CA3-CA1 synapses
TLDR
It is reported that only the mutation in GSK3α affects long‐term potentiation (LTP) and depression (LTD), which stresses the importance of investigating isoform specificity for G SK3 in all systems and suggests that GSK 3α should be investigated as a drug target in cognitive disorders including Alzheimer's Disease. Expand
Synaptic Stimulation of mTOR Is Mediated by Wnt Signaling and Regulation of Glycogen Synthetase Kinase-3
TLDR
It is reported that mTOR is tonically suppressed in rat hippocampus under resting conditions, a consequence of the basal activity of glycogen synthetase kinase 3 (GSK3), and this suppression could be overcome by weak synaptic stimulation in the presence of the β-adrenergic agonist isoproterenol. Expand
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