Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulus reinforcement strengthens learning. Intervals between reinforcement affect both the kind of learning that occurs and the amount of learning. Stimuli spaced by a few minutes result in more effective learning than when massed together. There are several synaptic correlates of repeated stimuli, such as different kinds of plasticity and the amplitude of synaptic change. Here we study the role of signalling pathways in the synapse on this selectivity for spaced stimuli. Using the in vitro hippocampal slice technique we monitored long-term potentiation (LTP) amplitude in CA1 for repeated 100-Hz, 1-s tetani. We observe the highest LTP levels when the inter-tetanus interval is 5-10 min. We tested biochemical activity in the slice following the same stimuli, and found that extracellular signal-regulated kinase type II (ERKII) but not CaMKII exhibits a peak at about 10 min. When calcium influx into the slice is buffered using AM-ester calcium dyes, amplitude of the physiological and biochemical response is reduced, but the timing is not shifted. We have previously used computer simulations of synaptic signalling to predict such temporal tuning from signalling pathways. In the current study we consider feedback and feedforward models that exhibit temporal tuning consistent with our experiments. We find that a model incorporating post-stimulus build-up of PKM zeta acting upstream of mitogen-activated protein kinase is sufficient to explain the observed temporal tuning. On the basis of these combined experimental and modelling results we propose that the dynamics of PKM activation and ERKII signalling may provide a mechanism for functionally important forms of synaptic pattern selectivity.
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PMID:A role for ERKII in synaptic pattern selectivity on the time-scale of minutes. 1554 10

The engram refers to the molecular changes by which a memory is stored in the brain. Substantial evidence suggests that memory involves learning-dependent changes at synapses, a process termed long-term potentiation (LTP). Thus, understanding the storages process that underlies LTP may provide insight into how the engram is stored. LTP involves induction, maintenance (storage), and expression sub-processes; special tests are required to specifically reveal properties of the storage process. The strongest of these is the Erasure test in which a transiently applied agent that attacks a putative storage molecule may lead to persistent erasure of previously induced LTP/memory. Two major hypotheses have been proposed for LTP/memory storage: the CaMKII and PKM-zeta hypotheses. After discussing the tests that can be used to identify the engram (Necessity test, Saturation/Occlusion test, Erasure test), the status of these hypotheses is evaluated, based on the literature on LTP and memory-guided behavior. Review of the literature indicates that all three tests noted above support the CaMKII hypothesis when done at both the LTP level and at the behavioral level. Taken together, the results strongly suggest that the engram is stored by an LTP process in which CaMKII is a critical memory storage molecule.
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PMID:Criteria for identifying the molecular basis of the engram (CaMKII, PKMzeta). 2918 15