TrkB as a Potential Synaptic and Behavioral Tag

Gene, Cognition and Psychosis Program, NIMH, National Institutes of Health, Bethesda, Maryland 20892-3714, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2011; 31(33):11762-71. DOI: 10.1523/JNEUROSCI.2707-11.2011
Source: PubMed


Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse specificity of long-term memory is "synaptic tagging": synaptic activity generates a tag, which "captures" the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.

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    • "CFC, contextual fear conditioning. been shown to be potential behavioral tags (Lu et al., 2011; Moncada et al., 2011; de Carvalho Myskiw et al., 2014). In particular, BDNF is sufficient to induce the transformation of early-LTP into late-LTP, suggesting that BDNF signaling is involved in synaptic tagging (Rex et al., 2007). "
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    ABSTRACT: Fear extinction forms a new memory but does not erase the original fear memory. Exposure to novelty facilitates transfer of short-term extinction memory to long-lasting memory. However, the underlying cellular and molecular mechanisms are still unclear. Using a classical contextual fear-conditioning model, we investigated the effect of novelty on long-lasting extinction memory in rats. We found that exposure to a novel environment but not familiar environment 1 h before or after extinction enhanced extinction long-term memory (LTM) and reduced fear reinstatement. However, exploring novelty 6 h before or after extinction had no such effect. Infusion of the β-adrenergic receptor (βAR) inhibitor propranolol and glucocorticoid receptor (GR) inhibitor RU486 into the CA1 area of the dorsal hippocampus before novelty exposure blocked the effect of novelty on extinction memory. Propranolol prevented activation of the hippocampal PKA-CREB pathway, and RU486 prevented activation of the hippocampal extracellular signal-regulated kinase 1/2 (Erk1/2)-CREB pathway induced by novelty exposure. These results indicate that the hippocampal βAR-PKA-CREB and GR-Erk1/2-CREB pathways mediate the extinction-enhancing effect of novelty exposure. Infusion of RU486 or the Erk1/2 inhibitor U0126, but not propranolol or the PKA inhibitor Rp-cAMPS, into the CA1 before extinction disrupted the formation of extinction LTM, suggesting that hippocampal GR and Erk1/2 but not βAR or PKA play critical roles in this process. These results indicate that novelty promotes extinction memory via hippocampal βAR- and GR-dependent pathways, and Erk1/2 may serve as a behavioral tag of extinction. Copyright © 2015 the authors 0270-6474/15/358308-14$15.00/0.
    No preview · Article · May 2015 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    • "Specifically, the brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are some of the prominent players which act as a PRP and tag, respectively (Lu et al. 2011; Sajikumar and Korte 2011). "
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    Preview · Article · Apr 2015 · Cerebral Cortex
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    • "Post-translational events in which plasticity-related proteins (PRPs) modify synapses, thereby completing the E-T circuit, are currently the focus of intensive research. One model suggests that molecular " tags " – possibly tyrosine kinase B (TrkB) – localized at presynaptic terminals – recruit PRPs during memory stabilization (Frey and Morris, 1997; Lisman and Raghavachari, 2006; Lu et al., 2011). Simultaneously, upregulated ␣-amino-3-hydroxy-5- methyl-4-isoxazoleproprionic receptors (AMPARs) are anchored to the postsynaptic density (PSD) via a pool of PRPs. "
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