Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mzeta (PKMzeta).
Activity-dependent synaptic plasticity is widely accepted to be the cellular correlate of learning and memory. It is believed that associativity between different synaptic inputs can transform short-lasting forms of synaptic plasticity (<3 h) to long-lasting ones. Synaptic tagging and capture (STC) might be able to explain this heterosynaptic support, because it distinguishes between local mechanisms of synaptic tags and cell-wide mechanisms responsible for the synthesis of plasticity-related proteins (PRPs). STC initiate storage processes only when the strength of the synaptic tag and the local concentration of essential proteins are above a certain plasticity threshold. We present evidence that priming stimulation through the activation of metabotropic glutamate receptors substantially increases the "range of threshold" for functional plasticity by producing protein kinase Mζ (PKMζ) as a PRP through local protein synthesis. In addition, our results implicate BDNF as a PRP which is mandatory for establishing cross-capture between synaptic strengthening and weakening, whereas the newly generated PKMζ specifically establishes synaptic tagging of long-term potentiation. Most intriguingly, we show here that STC are confined to specific dendritic compartments and that these compartments contain "synaptic clusters" with different plasticity thresholds. Our results suggest that within a dendritic compartment itself a homeostatic process exists to adjust plasticity thresholds. The range in which these clusters operate can be altered by processes of metaplasticity, which will operate on the cluster independently of other clusters at the same dendrite. These clusters will then prepare the synaptic network to form long-term memories.
Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, D-38106 Braunschweig, Germany.
Sreedharan
S
Sajikumar
Martin
M
Korte
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D017470:Receptors, Glutamate; D000099221:Protein Kinase C zeta
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