title: Making synapses strong: metaplasticity prolongs associativity of long-term memory by switching synaptic tag mechanisms.
abstract: One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that metaplasticity induced by ryanodine receptor activation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the "late" stage of associative memory formation occurs only through metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal.
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, Germany.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Rothkegel
authors.forename: Zhi Cheng
authors.initials: ZC
authors.lastname: Xiao
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.forename: Martin
authors.initials: M
authors.lastname: Korte
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2