PMID- 12629219 OWN - NLM STAT- MEDLINE DCOM- 20030522 LR - 20181130 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 100 IP - 7 DP - 2003 Apr 1 TI - Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse. PG - 4275-80 AB - 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. FAU - Hinds, Heather L AU - Hinds HL AD - 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. FAU - Goussakov, Ivan AU - Goussakov I FAU - Nakazawa, Kazu AU - Nakazawa K FAU - Tonegawa, Susumu AU - Tonegawa S FAU - Bolshakov, Vadim Y AU - Bolshakov VY LA - eng GR - R01 NS032925/NS/NINDS NIH HHS/United States GR - R01 NS044185/NS/NINDS NIH HHS/United States GR - R01 NS32925/NS/NINDS NIH HHS/United States GR - R01 NS44185/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030310 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Neurotransmitter Agents) RN - 3KX376GY7L (Glutamic Acid) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Animals MH - Brain/enzymology/*physiology MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/deficiency/*genetics/*physiology MH - Excitatory Postsynaptic Potentials MH - Glutamic Acid/*physiology MH - Hippocampus/*physiology MH - In Situ Hybridization MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neurotransmitter Agents/*metabolism MH - Restriction Mapping MH - Synapses/*physiology PMC - PMC153083 EDAT- 2003/03/12 04:00 MHDA- 2003/05/23 05:00 PMCR- 2003/10/01 CRDT- 2003/03/12 04:00 PHST- 2003/03/12 04:00 [pubmed] PHST- 2003/05/23 05:00 [medline] PHST- 2003/03/12 04:00 [entrez] PHST- 2003/10/01 00:00 [pmc-release] AID - 0530202100 [pii] AID - 0202 [pii] AID - 10.1073/pnas.0530202100 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4275-80. doi: 10.1073/pnas.0530202100. Epub 2003 Mar 10.