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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    • "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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    • "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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