Late-phase, protein synthesis-dependent long-term potentiation in hippocampal CA1 pyramidal neurones with destabilized microtubule networks.
OBJECTIVE
Protein synthesis-dependent late-long term potentiation (L-LTP) is an enduring form of synaptic plasticity that has been shown to rely on, at least partly, protein synthesis at synaptic and/or dendritic sites. Evidence suggests that somatic transcription of new mRNAs may provide a significant contribution to the availability of mRNAs at synaptic sites where they are made available for dendritic translation. Transport of mRNAs from somatic to dendritic sites might be expected to involve movement along a microtubule network. In this study we examined whether it was possible to maintain L-LTP in hippocampal slices with destabilized microtubule networks.


METHODS
Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded from rat hippocampal slices and following a period of baseline recording, stimuli were given that induced LTP. LTP was monitored for 5 h in both control slices and slices treated with vincristine to depolymerize tubulin.


RESULTS
L-LTP was induced and maintained in vincristine-treated slices. Four hours after tetanic stimulation fEPSPs were 196+/-19% of baseline values. The magnitude of potentiation was similar to that seen in untreated slices (175+/-15%). L-LTP in vincristine-treated slices was, however, not maintained in the presence of the protein synthesis inhibitor, rapamycin. Immunohistochemistry and confocal microscopy of vincristine-treated slices verified that the microtubule network had been destabilized.


CONCLUSIONS
Communication between somatic and synaptic sites through protein and/or mRNA trafficking via an intact microtubule network is not required for protein synthesis dependent L-LTP.
Vickers
C A
CA
Centre for Neuroscience Research, University of Edinburgh, Edinburgh, UK.
Wyllie
D J A
DJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D007120:Immunochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D050257:Tubulin Modulators; D014750:Vincristine; D020123:Sirolimus