Testing the conditions of long-term potentiation vulnerability for enhancement and interruption in CA1 area from mice hippocampal slices

• Based on the recent findings that show that both long-term potentiation (LTP) and long-term depression (LTD) can be stabilized for several hours in hippocampal slices obtained from rat or mice, we have developed a theoretical model that explain these contradictory findings to the major literature. Our model conceded, in contrast to the prevalent dogma in the neuroscience of synaptic plasticity, that protein turnover rather than the presumed triggered protein synthesis has predictive power for the outcome of synaptic plasticity under conditions of protein synthesis inhibition (Abbas et al., Rev. Neurosci., Submitted). We predicted that when the degree of ATP perturbation produced by the LTP-inducing stimulation was not very high, either due to the type of LTP-inducing protocol (e.g. “weak”) or if the compensatory non-neuronal energy sources alleviate the state of transient ATP disturbance, the rate of activity-dependent degradation will be generally low and protein synthesis inhibitors might have no effect unless the protein synthesis inhibition interval covers the half-life of necessary proteins. To empirically verify our proposed model, we conducted experiments testing the conditions under which LTP can be vulnerable to enhancement or interruption by application of protein degradation inhibitor. Benefiting from the drug characteristics of dose-dependent selective targeting of the components of the proteasome system, S20 and S26, we treated hippocampal slices obtained from adult mice with the proteasome inhibitor MG-115. Low concentrations (10-20 µM) of the drug improved the magnitude and duration of LTP induced by weak induction protocol. However, higher concentration (50 µM) diminished the magnitude of LTP induced by either weak or strong protocol. Taken together, the findings indicate that, blocking degradation of some protein components (e.g. negative proteins) improves LTP in its magnitude and/or lifetime. Conversely, when the LTP induction is associated with an increase in turnover, blocking degradation exhibits a decaying effect on LTP stabilization in similar pattern to that achieved by protein synthesis inhibitors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Long-term potentiation

protein synthesis

protein degradation

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