Neocortical Long-Term Potentiation and Experience-Dependent Synaptic Plasticity Require α-Calcium/Calmodulin-Dependent Protein Kinase II Autophosphorylation

Hardingham, Neil Robert; Głażewski, Stanisław; Pakhotin, Pavel; Mizuno, Keiko; Chapman, Paul F.; Giese, Karl-Peter; Fox, Kevin

doi:10.1523/jneurosci.23-11-04428.2003

Cited by 92 publications

(95 citation statements)

References 36 publications

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“…However, there is evidence from whisker deprivation studies in barrel cortex that changes in spike timing drive in vivo plasticity rather than changes in input frequency (Celikel et al, 2004). Because spike timing-dependent plasticity (STDP) acts in a similar manner to other induction methods in barrel cortex (Hardingham et al, 2003) and it may be a more physiologically relevant induction protocol (Celikel et al, 2004), we used it in this study.…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we concentrated on LTP in adult (6 -13 weeks) rather than developing animals principally because it may relate to the adult plasticity induced in vivo in layer II/III cells by whisker deprivation (Hardingham et al, 2003). However, the majority of the literature on in vitro plasticity in neocortex relates to juvenile animals, and it may therefore be worthwhile to point out some of the differences between our observations and those made in juveniles.…”

Section: Discussionmentioning

confidence: 95%

“…We found previously that CaMKII was required for STDP at this synapse (Hardingham et al, 2003), but, to test whether CaMKII acts presynaptically or postsynaptically, we included a CaMKII inhibitor, AIP (Ishida et al, 1998), in the electrode and recorded intracellularly from layer II/III pyramidal cells in barrel cortex. Potentiation was induced in cells treated with low doses (100 nM) of AIP but blocked in cells with higher doses at an IC 50 of 500 nM (Fig.…”

Section: The Role Of Nmda Receptors and Postsynaptic Camkii In Stdpmentioning

confidence: 99%

“…The most direct pathway, although not the only pathway that might be responsible, runs from layer IV to layers II/III in the neighboring barrel column. In a previous study, we found that calcium/calmodulin-dependent kinase II (CaMKII) autophosphorylation plays a key role in synaptic potentiation in this pathway and that experience-dependent plasticity depends on the same mechanism (Hardingham et al, 2003). However, it is not known whether presynaptic or postsynaptic CaMKII is required for potentiation in the neocortex or what the effector molecules might be downstream of CaMKII.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

2006

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In this study, we investigated the mechanisms underlying synaptic plasticity at the layer IV to II/III pathway in barrel cortex of mice aged 6 -13 weeks. This pathway is one of the likely candidates for expression of experience-dependent plasticity in the barrel cortex and may serve as a model for other IV to II/III synapses in the neocortex. We found that postsynaptic autocamtide-2-inhibitory peptide is sufficient to block long-term potentiation (LTP) (IC 50 of 500 nM), implicating postsynaptic calcium/calmodulin-dependent kinase II in LTP induction. AMPA receptor subunit 1 (GluR1) knock-out mice also showed LTP in this pathway, but potentiation was predominantly presynaptic in origin as determined by paired-pulse analysis, coefficient of variation analysis, and quantal analysis, whereas wild types showed a mixed presynaptic and postsynaptic locus. Quantal analysis at this synapse was validated by measuring uniquantal events in the presence of strontium. The predominantly presynaptic LTP in the GluR1 knock-outs was blocked by postsynaptic antagonism of nitric oxide synthase (NOS), either with intracellular N--nitro-L-arginine methyl ester or N-nitro-L-arginine, providing the first evidence for a retrograde transmitter role for NO at this synapse. Antagonism of NOS in wild types significantly reduced but did not eliminate LTP (group average reduction of 50%). The residual LTP formed a variable proportion of the total LTP in each cell and was found to be postsynaptic in origin. We found no evidence for silent synapses in this pathway at this age. Finally, application of NO via a donor induced potentiation in layer II/III cells and caused an increase in frequency but not amplitude of miniature EPSPs, again implicating NO in presynaptic plasticity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: The Role Of Nmda Receptors and Postsynaptic Camkii In Stdpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

2006

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“…Kinase activity has also been implicated in plasticity in the barrel cortex. Knock out or mutation (Glazewski et al, 2000;Hardingham et al, 2003) of calcium/calmodulin-dependent kinase II (CaMKII), an enzyme necessary for LTP (Malenka and Nicoll, 1999;Silva et al, 1992), blocks both receptive field plasticity and NMDA receptor-dependent LTP in barrel cortex. In addition, a recent study has identified a role for PKC in regulating synaptic strength at TC synapses in barrel cortex (Scott et al, 2006).…”

Section: Role Of Protein Kinases In Barrel Cortex Plasticitymentioning

confidence: 99%

Developmental synaptic plasticity at the thalamocortical input to barrel cortex: Mechanisms and roles

Daw

Scott

Isaac

2007

Molecular and Cellular Neuroscience

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The thalamocortical (TC) input to layer IV provides the major pathway for ascending sensory information to the mammalian sensory cortex. During development there is a dramatic refinement of this input that underlies the maturation of the topographical map in layer IV. Over the last ten years our understanding of the mechanisms of the developmental and experience-driven changes in synaptic function at TC synapses has been greatly advanced. Here we describe these studies that point to a key role for NMDA receptor-dependent synaptic plasticity, a role for kainate receptors and for a rapid maturation in GABAergic inhibition. The expression mechanisms of some of the forms of neonatal synaptic plasticity are novel and, in combination with other mechanisms, produce a layer IV circuit that exhibits functional properties necessary for mature sensory processing.

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NMDA receptors on zebrafish Mauthner cells require CaMKII‐α for normal development

Roy

Ferdous

Ali

2014

Developmental Neurobiology

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Calcium/calmodulin dependent protein kinase 2 (CaMKII) is a multifunctional protein that is highly enriched in the synapse. It plays important roles in neuronal functions such as synaptic plasticity, synaptogenesis, and neural development. Gene duplication in zebrafish has resulted in the occurrence of seven CaMKII genes (camk2a, camk2b1, camk2b2, camk2g1, camk2g2, camk2d1, and camk2d2) that are developmentally expressed. In this study, we used single cell, real-time quantitative PCR to investigate the expression of CaMKII genes in individual Mauthner cells (M-cells) of 2 days post fertilization (dpf) zebrafish embryos. We found that out of seven different CaMKII genes, only the mRNA for CaMKII-α was expressed in the M-cell at detectable levels, while all other isoforms were undetectable. Morpholino knockdown of CaMKII-α had no significant effect on AMPA synaptic currents (mEPSCs) but decreased the amplitude of NMDA mEPSCs. NMDA events exhibited a biexponential decay with τfast ≈ 30 ms and τslow ≈ 300 ms. Knockdown of CaMKII-α specifically reduced the amplitude of the slow component of the NMDA-mediated currents (mEPSCs), without affecting the fast component, the frequency, or the kinetics of the mEPSCs. Immunolabelling of the M-cell showed increased dendritic arborizations in the morphants compared with controls, and knockdown of CaMKII-α altered locomotor behaviors of touch responses. These results suggest that CaMKII-α is present in embryonic M-cells and that it plays a role in the normal development of excitatory synapses. Our findings pave the way for determining the function of specific CaMKII isoforms during the early stages of M-cell development.

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Neocortical Long-Term Potentiation and Experience-Dependent Synaptic Plasticity Require α-Calcium/Calmodulin-Dependent Protein Kinase II Autophosphorylation

Cited by 92 publications

References 36 publications

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

Developmental synaptic plasticity at the thalamocortical input to barrel cortex: Mechanisms and roles

NMDA receptors on zebrafish Mauthner cells require CaMKII‐α for normal development

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