Priming of short-term potentiation and synaptic tagging/capture mechanisms by ryanodine receptor activation in rat hippocampal CA1.
Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and long-term depression (LTD) are considered to be cellular mechanisms underlying learning and memory. Strengthening of a synapse for a few seconds or minutes is termed short-term potentiation (STP) and is normally unable to take part in the processes of synaptic tagging/capture due to its inability to set the "synaptic tags." Here, we report that priming of synapses with ryanodine receptor agonists such as ryanodine (10 microM) or caffeine (10 mM) facilitates subsequent synaptic tagging/capture, enabling an STP protocol to establish a late-LTP in response to strong tetanization of a heterosynaptic input. We identified calcium/calmodulin-dependent protein kinase II (CaMKII) as mediating the primed synaptic tag setting, which persisted for 1 h. We also identified protein kinase Mzeta (PKMzeta), presumably captured from the strongly tetanized heterosynaptic input, as a plasticity-related protein maintaining the LTP at the tagged synapses. In addition, synaptic tags in primed STP were erased or interfered with by delivering low-frequency depotentiating stimulation 5 or 10 min after its induction, thus preventing capture of newly synthesized proteins. These data reveal a novel form of metaplasticity, whereby ryanodine receptor activation lowers the threshold for subsequent synaptic tagging/capture, thus priming weakly activated synapses for heterosynaptic interactions that promote long-term functional plasticity.
Sajikumar
Sreedharan
S
Department of Clinical Research, Singapore General Hospital, Singapore 169608. S.sajikumar@tu-bs.de
Li
Qin
Q
Abraham
Wickliffe C
WC
Xiao
Zhi Cheng
ZC
D000818:Animals; D001703:Biophysics; D002110:Caffeine / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2