CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP.
To investigate the function of the autophosphorylated form of CaMKII in synaptic plasticity, we generated transgenic mice that express a kinase that is Ca2+ independent as a result of a point mutation of Thr-286 to aspartate, which mimics autophosphorylation. Mice expressing the mutant form of the kinase show an increased level of Ca(2+)-independent CaMKII activity similar to that seen following LTP. The mice nevertheless exhibit normal LTP in response to stimulation at 100 Hz. However, at lower frequencies, in the range of 1-10 Hz, there is a systematic shift in the size and direction of the resulting synaptic change in the transgenic animals that favors LTD. The regulation of this frequency-response function by Ca(2+)-independent CaMKII activity seems to account for two previously unexplained synaptic phenomena, the relative loss of LTD in adult animals compared with juveniles and the enhanced capability for depression of facilitated synapses.
Mayford
M
M
Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Wang
J
J
Kandel
E R
ER
O'Dell
T J
TJ
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004558:Electric Stimulation; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D013569:Synapses / Q000502:physiology
D018076:DNA, Complementary; D017871:Calcium-Calmodulin-Dependent Protein Kinases