A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

Selcher, Joel C.; Atkins, Coleen M.; Trzaskos, James M.; Paylor, Richard; Sweatt, J. David

doi:10.1101/lm.6.5.478

Cited by 341Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

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Selcher, Joel C., Atkins, Coleen M., Trzaskos, James M., Paylor, Richard, Sweatt, J. David·1999·Learning & Memory

DOI 10.1101/lm.6.5.478PMC PMC311312

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Abstract

Although the biochemical mechanisms underlying learning and memory have not yet been fully elucidated, mounting evidence suggests that activation of protein kinases and phosphorylation of their downstream effectors plays a major role. Recent findings in our laboratory have shown a requirement for the mitogen-activated protein kinase (MAPK) cascade in hippocampal synaptic plasticity. Therefore, we used an inhibitor of MAPK activation, SL327, to test the role of the MAPK cascade in hippocampus-dependent learning in mice. SL327, which crosses the blood-brain barrier, was administered intraperitoneally at several concentrations to animals prior to cue and contextual fear conditioning. Administration of SL327 completely blocked contextual fear conditioning and significantly attenuated cue learning when measured 24 hr after training. To determine whether MAPK activation is required for spatial learning, we administered SL327 to mice prior to training in the Morris water maze. Animals treated with SL327 exhibited significant attenuation of water maze learning; they took significantly longer to find a hidden platform compared with vehicle-treated controls and also failed to use a selective search strategy during subsequent probe trials in which the platform was removed. These impairments cannot be attributed to nonspecific effects of the drug during the training phase; no deficit was seen in the visible platform task, and injection of SL327 following training produced no effect on the performance of these mice in the hidden platform task. These findings indicate that the MAPK cascade is required for spatial and contextual learning in mice.

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SL327 at 50 mg/kg can cross the blood-brain barrier and effectively reduce the basal level of ERK activation in the CNS.
“It was previously reported that SL327 at this concentration can cross the blood-brain barrier and effectively reduce the basal level of ERK activation in the CNS101213.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [13]

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Authors: Selcher, J. C., Atkins, C. M., Trzaskos, J. M., Paylor, R., & Sweatt, J. D.
Affiliations: DuPont (United States) (US)
ORCID: Atkins, Coleen M.
Sweatt, J. David
Venue: Learning & Memory
Publisher: Cold Spring Harbor Laboratory
Published: 1999-09-01
Volume: 6
Issue: 5
Pages: 478-490
ISSN: 1072-0502 (ISSN-L)
1549-5485
DOI: 10.1101/lm.6.5.478
PMC: PMC311312
OpenAlex: W2141014036
Cited by: 341
References: 43
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 17 · 2012: 16
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Learning & Memory (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Alliance for Research on Schizophrenia and Depression
National Institutes of Health
National Institute of Mental Health (MH 57014, R01MH057014)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: mitogen-activated protein kinase, SL327, hippocampus-dependent learning, spatial learning, contextual fear conditioning, cue learning, Morris water maze, synaptic plasticity, protein kinase inhibition, memory formation
MeSH terms: Animals, Conditioning, Operant, Cues, Enzyme Activation, Enzyme Inhibitors, Fear, Maze Learning, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Signaling System, Mice

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A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

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