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A genetic test of the effects of mutations in PKA on mossy fiber ltp and its relation to spatial and contextual learning

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Huang, Yan-You, Kandel, Eric R., Varshavsky, Lauren, Brandont, Eugene P., Qi, Ming, Idzerda, Rejean L., Stanley McKnight, G., Bourtchouladz, Roussoudan·1995·Cell

DOI 10.1016/0092-8674(95)90146-9

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Abstract

Using a genetic approach, we assessed the effects of mutations in protein kinase A (PKA) on long-term potentiation (LTP) in the mossy fiber pathway and its relationship to spatial and contextual learning. Ablation by gene targeting of the C beta 1 or the RI beta isoform of PKA produces a selective defect in mossy fiber LTP, providing genetic evidence for the role of these isoforms in the mossy fiber pathway. Despite the elimination of mossy fiber LTP, the behavioral responses to novelty, spatial learning, and conditioning to context are unaffected. Thus, contrary to current theories about hippocampal function, mossy fiber LTP does not appear to be required for spatial or contextual learning. In the absence of mossy fiber LTP, adequate spatial and contextual information might reach the CA1 region via other pathways from the entorhinal cortex.

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Authors: Huang, Y.-Y., Kandel, E. R., Varshavsky, L., Brandont, E. P., Qi, M., Idzerda, R. L., Stanley McKnight, G., & Bourtchouladz, R.
Affiliations: Howard Hughes Medical Institute (US)
University of Washington (US)
ORCID: Kandel, Eric R.
Venue: Cell
Publisher: Elsevier BV
Published: 1995-12
Volume: 83
Issue: 7
Pages: 1211-1222
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(95)90146-9
OpenAlex: W2094988830
Cited by: 267
References: 56
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 8
FWCI: 11.73
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6438 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (GM32675)
Howard Hughes Medical Institute (MH50733)
National Institute of Mental Health
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords: protein kinase A, hippocampus, spatial learning, contextual learning, novelty response, gene targeting, entorhinal cortex, CA1, hippocampal function
MeSH terms: Animals, Conditioning, Psychological, Electrophysiology, Female, Colforsin, Hippocampus, Isoenzymes, Isoproterenol, Male, Mice, Inbred C57BL, Mutation, Spatial Behavior, Long-Term Potentiation, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Maze Learning, Mice, Cyclic AMP-Dependent Protein Kinase RIbeta Subunit

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A genetic test of the effects of mutations in PKA on mossy fiber ltp and its relation to spatial and contextual learning

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