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Cited by 269Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

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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  • Plasticity in the EC-DG and DG-CA3 synapses seems to be dispensable.

    “first, theplasticity inthe EC-DGandDG-CA3 synapses seems to be dispensable (Huang et al., 1995; Nosten-Bertrand et al., 1996);”

    From The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. (1996) · cites this paper as Huang et al., 1995

  • Impairments of mossy fiber-CA3 LTP and perforant path-dentate LTP are not correlated with spatial memory deficit.

    “By contrast, it has been shown that impairments of mossy fiber-CA3 LTP(Huang etal., 1995) and perforant path-dentate LTP (Nosten-Bertrand et al., 1996) are not correlated with spatial memory deficit.”

    From The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. (1996) · cites this paper as Huang et al., 1995

  • Mutant mice lacking PKA C1β or Riβ subunits are defective in mossy fiber LTP.

    “For example, forskolin evokes LTP at the mossy fiber3 CA3 synapse, whereas the inactive forskolin homolog, 1,9-dideoxy-forskolin, does not (Weisskopf et al., 1994), and mutant mice lacking PKA C1␤ or Ri␤ subunits are defective in mossy fiber LTP (Huang et al., 1995).”

    From Type I Adenylyl Cyclase Mutant Mice Have Impaired Mossy Fiber Long-Term Potentiation (1998) · cites this paper as Huang et al., 1995

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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
Licence
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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