CA1 long-term potentiation is diminished but present in hippocampal slices from alpha-CaMKII mutant mice

Hinds, H. L., Tonegawa, S., Malinow, R. (September 1998) CA1 long-term potentiation is diminished but present in hippocampal slices from alpha-CaMKII mutant mice. Learning and Memory, 5 (4-5). pp. 344-54. ISSN 1072-0502 (Print)

[thumbnail of Malinow_LearnMem1998.pdf]
Preview
 PDF
Malinow_LearnMem1998.pdf
Download (904kB) | Preview

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.

Item Type: Paper
Uncontrolled Keywords: Animals Ca(2+)-Calmodulin Dependent Protein Kinase/deficiency/ genetics/ metabolism Crosses, Genetic Electric Stimulation Female Hippocampus/ physiology In Vitro Long-Term Potentiation/ physiology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Neurons/ physiology Regression Analysis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Synapses/physiology
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > Long term potentiation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > CaMKII
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Malinow lab
Depositing User: Kathleen Darby
Date: September 1998
Date Deposited: 01 May 2014 18:18
Last Modified: 01 May 2014 18:18
PMCID: PMC311262
Related URLs:
URI: https://repository.cshl.edu/id/eprint/29896

Actions (login required)

Administrator's edit/view item Administrator's edit/view item