Polymyxin B, an inhibitor of protein kinase C, prevents the maintenance of synaptic long-term potentiation in hippocampal CA1 neurons.
The involvement of protein kinase C (PKC)-mediated processes in mechanisms of long-term potentiation (LTP) was suggested by recent studies which have demonstrated a correlation between PKC activation and LTP. However, it was not possible to tell whether there is a causal relationship between the two events. Therefore, we have examined the induction and maintenance of LTP in rat hippocampal slices in the presence of a relatively selective PKC inhibitor, using extracellular electrophysiological techniques. Bath application of 0.1-100 microM polymyxin B did not influence the occurrence of post-tetanic and long-term potentiation usually seen in test responses 1 and 10 min after a 100-Hz/1 s tetanic stimulation of stratum radiatum fibers. However, 20 microM polymyxin B significantly depressed the increase in population spike amplitude and population excitatory postsynaptic potential (EPSP) slope from 30 to 120 min onwards, following repeated tetanization. Immediately after the drug application only weak and reversible effects were seen by the same parameters in test responses of a non-tetanized control input. A late (greater than 6 h) heterosynaptic potentiation of the population spike in the control input was blocked by polymyxin B treatment. Whereas the EPSP-LTP was fully blocked, some potentiation of the population spike still remained, suggesting the independence of PKC of the additional spike (E/S) potentiation for the first 6 h. These results provide direct evidence that the PKC activation is not essential for the initial phase of LTP, but is a necessary condition for a medium and a late, protein synthesis-dependent phase in this monosynaptic pathway, i.e. for the maintenance of synaptic LTP.
Reymann
K G
KG
Institute of Neurobiology and Brain Research, Academy of Sciences G.D.R., Magdeburg.
Frey
U
U
Jork
R
R
Matthies
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011112:Polymyxin B / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011113:Polymyxins; D011493:Protein Kinase C; D011112:Polymyxin B