Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse.
A significant fraction of the total calciumcalmodulin-dependent protein kinase II (CaMKII) activity in neurons is associated with synaptic connections and is present in nerve terminals, thus suggesting a role for CaMKII in neurotransmitter release. To determine whether CaMKII regulates neurotransmitter release, we generated and analyzed knockout mice in which the dominant alpha-isoform of CaMKII was specifically deleted from the presynaptic side of the CA3-CA1 hippocampal synapse. Conditional CA3 alpha-CaMKII knockout mice exhibited an unchanged basal probability of neurotransmitter release at CA3-CA1 synapses but showed a significant enhancement in the activity-dependent increase in probability of release during repetitive presynaptic stimulation, as was shown with the analysis of unitary synaptic currents. These data indicate that alpha-CaMKII serves as a negative activity-dependent regulator of neurotransmitter release at hippocampal synapses and maintains synapses in an optimal range of release probabilities necessary for normal synaptic operation.
Hinds
Heather L
HL
Howard Hughes Medical Institute, Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Goussakov
Ivan
I
Nakazawa
Kazu
K
Tonegawa
Susumu
S
Bolshakov
Vadim Y
VY
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015183:Restriction Mapping; D013569:Synapses / Q000502:physiology*
D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases