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Differential Role of Mitogen-Activated Protein Kinase in Three Distinct Phases of Memory for Sensitization in Aplysia
Open accessAbstract
The mitogen-activated protein kinase (MAPK) pathway has been implicated recently in synaptic plasticity and memory. Here we used tail shock-induced sensitization of the tail-elicited siphon withdrawal reflex in Aplysia to examine the role of MAPK in three different phases of memory. We show that a specific pattern of serotonin (5-HT) application that produces intermediate-term and long-term synaptic facilitation (ITF and LTF, respectively) of the sensory-motor (SN-MN) synapses in Aplysia leads to sustained activation of extracellular signal-regulated kinase in the ventrocaudal cluster sensory neurons (SNs), which include the tail SNs. Furthermore, repeated tail shocks that induce intermediate-term and long-term memory (ITM and LTM, respectively) for sensitization also lead to sustained MAPK activation in the SNs. Given these results, we next examined the requirement of MAPK activity in (1) SN-MN synaptic facilitation and (2) memory for sensitization in Aplysia, by inhibiting MEK, the upstream kinase that phosphorylates and activates MAPK. In cellular experiments, we show that MAPK activity is required for ITF of tail SN-tail MN synapses, and, in parallel behavioral experiments, we show that ITM requires MAPK activity for its induction but not its expression. In contrast, short-term memory for sensitization does not require MAPK activity. Finally, 5-HT-induced LTF has been shown previously to require MAPK activity. Here we show that LTM for sensitization also requires MAPK activity. These results provide evidence that MAPK plays important roles specifically in long-lasting phases of synaptic plasticity and memory.
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“The sustained activation of nuclear MAPK following five repeated spaced training shocks or spaced pulses of 5HT (Sharma et al., 2003) appears to be initiated in the presynaptic terminals of SN-MN synapses and requires the synthesis and local synaptic signaling of the neurotrophin-like peptide sensorin (Hu et al., 2004;Wang et al., 2009).”
From MAPK Establishes a Molecular Context That Defines Effective Training Patterns for Long-Term Memory Formation (2013) · cites this paper as Sharma et al., 2003
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“Two biochemical cascades required for LTF are those that mediate activation of protein kinase A (PKA)12–15 and the MAP kinase isoform termed extracellular signal-regulated kinase (ERK)16–18.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [18]
In the citing paper
“However, emetine exposure to the CNS for 30 min before 5HT application completely blocked 5HTinduced delayed MAPK activation (n ϭ 19, 5HT: 1.64 Ϯ 0.16 P-MAPK/T-MAPK ratio, 5HT-emetine: 1.19 Ϯ 0.07, p ϭ 0.003 paired t test, Fig. 2b).”
From MAPK Establishes a Molecular Context That Defines Effective Training Patterns for Long-Term Memory Formation (2013) · cites this paper as Sharma et al., 2003
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“Additionally, repeated training shocks or 5HT exposures give rise to sustained posttraining MAPK activation in tail SNs (Sharma et al., 2003).”
From MAPK Establishes a Molecular Context That Defines Effective Training Patterns for Long-Term Memory Formation (2013) · cites this paper as Sharma et al., 2003
In the citing paper
“We have previously shown that a sustained (1-3 h) MAPK activation develops in tail SNs following spaced training (4 or 5 spaced training shocks or pulses of 5HT; Sharma et al., 2003) and is necessary for LTM formation (Shobe et al., 2005).”
From MAPK Establishes a Molecular Context That Defines Effective Training Patterns for Long-Term Memory Formation (2013) · cites this paper as Sharma et al., 2003
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Metadata
- Authors
- Sharma, S. K., Sherff, C. M., Shobe, J., Bagnall, M. W., Sutton, M. A., & Carew, T. J.
- Affiliations
- University of California, Irvine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-05-01
- Volume
- 23
- Issue
- 9
- Pages
- 3899-3907
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742188
- OpenAlex
- W1500995611
- Cited by
- 125
- References
- 68
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 8 · 2012: 2
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Science Foundation (0049013)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- mitogen-activated protein kinase, Aplysia, siphon withdrawal reflex, serotonin, extracellular signal-regulated kinase, MEK inhibition, intermediate-term memory, long-term memory, short-term memory, synaptic facilitation, sensory-motor synapses, synaptic plasticity
- MeSH terms
- Action Potentials, Animals, Aplysia, Electric Stimulation, Enzyme Activation, Enzyme Inhibitors, Memory, Motor Neurons, Neurons, Afferent, Reflex, Serotonin, Stimulation, Chemical, Synapses, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mitogen-Activated Protein Kinases, In Vitro Techniques
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