Cited by 86Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsProtein Kinase Regulation and GTPase Signaling

CA1 Long-Term Potentiation Is Diminished but Present in Hippocampal Slices from α-CaMKII Mutant Mice

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Hinds, Heather L., Tonegawa, Susumu, Malinow, Roberto·1998·Learning & Memory

Abstract

Previous work has shown that mice missing the alpha-isoform of calcium-calmodulin-dependent protein kinase II (alpha-CaMKII) have a deficiency in CA1 hippocampal long-term potentiation (LTP). Follow-up studies on subsequent generations of these mutant mice in a novel inbred background by our laboratories have shown that whereas a deficiency in CA1 LTP is still present in alpha-CaMKII mutant mice, it is different both quantitatively and qualitatively from the deficiency first described. Mice of a mixed 129SvOla/SvJ;BALB/c;C57B1/6 background derived from brother/sister mating of the alpha-CaMKII mutant line through multiple generations (>10) were produced by use of in vitro fertilization. Although LTP at 60 min post-tetanus was clearly deficient in these (-/-) alpha-CaMKII mice (42.6%, n = 33) compared with (+/+) alpha-CaMKII control animals (81.7%, n = 17), alpha-CaMKII mutant mice did show a significant level of LTP. The amount of LTP observed in alpha-CaMKII mutants was normally distributed, blocked by APV (2.7%, n = 8), and did not correlate with age. Although this supports a role for alpha-CaMKII in CA1 LTP, it also suggests that a form of alpha-CaMKII-independent LTP is present in mice that could be dependent on another kinase, such as the beta-isoform of CaMKII. A significant difference in input/output curves was also observed between (-/-) alpha-CaMKII and (+/+) alpha-CaMKII animals, suggesting that differences in synaptic transmission may be contributing to the LTP deficit in mutant mice. However, tetani of increasing frequency (50, 100, and 200 Hz) did not reveal a higher threshold for potentiation in (-/-) alpha-CaMKII mice compared with (+/+) alpha-CaMKII controls.

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  • The results with genetic deletion of CaMKIIα are variable, some showing roughly a 50% block and some showing a complete block.

    “the results with the genetic deletion of CaMKIIα are more variable, some showing roughly a 50% block (87, 204–206) but some showing a complete block (121, 207, 208).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [206]

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  1. References Banbury conference. 1997. Neuron 19: 755-759.
  2. Butler, L.S., A.J. Silva, A. Abelovich, Y. Watanabe, S. ␣-CaMKII AND LTP Tonegawa, and J.O. McNamara. 1995. Limbic epilepsy in ␣-calcium-calmodulin kinase II mutant mice. Proc. Natl. Acad. Sci. 92: 6852-6855.

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Authors
Hinds, H. L., Tonegawa, S., & Malinow, R.
Affiliations
Howard Hughes Medical Institute (US)
Venue
Learning & Memory
Published
1998-09-01
Volume
5
Issue
4
Pages
344-354
ISSN
  • 1072-0502 (ISSN-L)
  • 1549-5485
OpenAlex
W2146518447
Cited by
86
References
66
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 4
Type
posted content
Language
en
Open access
Locations
  • Learning & Memory (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS-32925, R01NS032925)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
CaMKIIα, calcium/calmodulin-dependent protein kinase II, long-term potentiation, hippocampal CA1, mouse mutants, synaptic transmission, input-output curves, tetanic stimulation, APV
MeSH terms
Animals, Crosses, Genetic, Electric Stimulation, Female, Hippocampus, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred Strains, Neurons, Regression Analysis, Synapses, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Mice, Knockout, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques

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