RT Journal Article
SR Electronic
T1 Transgenic Calmodulin-Dependent Protein Kinase II Activation: Dose-Dependent Effects on Synaptic Plasticity, Learning, and Memory
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5719
OP 5726
DO 10.1523/JNEUROSCI.22-13-05719.2002
VO 22
IS 13
A1 Bejar, Rafael
A1 Yasuda, Rie
A1 Krugers, Harmen
A1 Hood, Kristin
A1 Mayford, Mark
YR 2002
UL http://www.jneurosci.org/content/22/13/5719.abstract
AB Genetic disruption of calmodulin-dependent protein kinase II (CaMKII) function alters hippocampal synaptic plasticity and memory in mice. We used transgenic mice carrying a tetracycline-regulated, calcium-independent form of CaMKII (CaMKII–Asp286) to investigate the role of CaMKII activation on synaptic plasticity and behavior. Mice expressing low levels of a CaMKII–Asp286 transgene have facilitated low-frequency (5 Hz)-induced long-term potentiation (LTP), whereas mice with high levels of transgene expression have a deficit in this form of plasticity. Behavioral impairments on fear-conditioned memory and visible water maze correlate with the level of CaMKII–Asp286 expression. Mice with high levels of CaMKII–Asp286 have reversible, compensatory changes in the expression of genes associated with inhibitory neurotransmission. These results demonstrate that in the hippocampus, CaMKII activation facilitates the induction of low-frequency LTP, but at high levels of expression, compensatory mechanisms act to inhibit the induction of this form of LTP. The most severe behavioral impairments are associated with activation of this compensatory mechanism.