The α-Ca2+/calmodulin kinase II: A bidirectional modulator of presynaptic plasticity

The alpha-Ca2+/calmodulin kinase II (alpha CaMKII) is required for long-term potentiation in the CA1 region of the hippocampus. Here, we report that this kinase also has a crucial role in presynaptic plasticity. Paired-pulse facilitation is blunted in the CA1 region of mice heterozygous for a targeted mutation of alpha CaMKII, confirming that this kinase can promote neurotransmitter release. Unexpectedly, field and whole-cell recordings of posttetanic potentiation show that the synaptic responses of mutants are larger than those of controls, indicating that alpha CaMKII can also inhibit transmitter release immediately after tetanic stimulation. Thus, alpha CaMKII has the capacity either to potentiate or to depress excitatory synaptic transmission depending on the pattern of presynaptic activation.

[1]  R. Tsien,et al.  Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. , 1989, Science.

[2]  H. Schulman,et al.  Neuronal Ca2+/calmodulin-dependent protein kinases. , 1992, Annual review of biochemistry.

[3]  S. B. Kater,et al.  Impaired Spatial Learning in L-Calcium-Calmodulin Kinase Mutant Mice , 2022 .

[4]  J. T. Hackett,et al.  Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission. , 1990, Journal of neurophysiology.

[5]  M A Gluck,et al.  Computational models of the neural bases of learning and memory. , 1993, Annual review of neuroscience.

[6]  Fabio Benfenati,et al.  Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I , 1992, Nature.

[7]  Alcino J. Silva,et al.  Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[8]  C. H. Vanderwolf,et al.  Hippocampal electrical activity and voluntary movement in the rat. , 1969, Electroencephalography and clinical neurophysiology.

[9]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[10]  R Llinás,et al.  Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Schulman,et al.  Calmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase , 1992, Science.

[12]  Alcino J. Silva,et al.  Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[13]  P. Greengard,et al.  Effects of synapsin I and calcium/calmodulin-dependent protein kinase II on spontaneous neurotransmitter release in the squid giant synapse. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Nicoll,et al.  An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation , 1989, Nature.

[15]  C. Klee,et al.  Advances in second messenger and phosphoprotein research , 1988 .

[16]  J. B. Ranck,et al.  Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. II. Hippocampal slow waves and theta cell firing during bar pressing and other behaviors. , 1973, Experimental neurology.

[17]  Roberto Malinow,et al.  Measuring the impact of probabilistic transmission on neuronal output , 1993, Neuron.

[18]  Lubert Stryer,et al.  Dual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals , 1994, Neuron.

[19]  B L McNaughton,et al.  Long‐term synaptic enhancement and short‐term potentiation in rat fascia dentata act through different mechanisms , 1982, The Journal of physiology.

[20]  P. Greengard,et al.  Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes , 1990, Nature.

[21]  G. Lynch,et al.  Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events. , 1986, Science.

[22]  H. Eichenbaum,et al.  Learning‐related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long‐term potentiation , 1991, Hippocampus.

[23]  Thomas C. Südhof,et al.  Short-term synaptic plasticity is altered in mice lacking synapsin I , 1993, Cell.

[24]  Gary Lynch,et al.  Evidence that changes in presynaptic calcium currents are not responsible for long-term potentiation in hippocampus , 1989, Brain Research.

[25]  J. Byrne,et al.  Roles of second messenger pathways in neuronal plasticity and in learning and memory. Insights gained from Aplysia. , 1993, Advances in second messenger and phosphoprotein research.

[26]  Susumu Tonegawa,et al.  The role of calcium–calmodulin kinase II in three forms of synaptic plasticity , 1994, Current Biology.

[27]  J. B. Ranck,et al.  Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. , 1973, Experimental neurology.

[28]  Grzegorz Hess,et al.  Quantal analysis of paired-pulse facilitation in guinea pig hippocampal slices , 1987, Neuroscience Letters.