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Journal of Neuroscience, Vol 10, 3353-3360, Copyright © 1990 by Society for Neuroscience
Inhibition of protein kinase C blocks two components of LTP persistence, leaving initial potentiation intact
PA Colley, FS Sheu and A Routtenberg
Cresap Neuroscience Laboratory, Northwestern University, Evanston, Illinois 60208.
Protein kinase C (PKC) activity is increased following hippocampal long-
term potentiation (LTP; Akers et al., 1986). A similar increase in PKC
activity is measured following the induction of a long-lasting potentiation
with abbreviated high-frequency stimulation (HFS) in combination with
PKC-activating phorbol esters (Colley et al., 1989). Because phorbol esters
have no effect on the initial potentiation produced with HFS, and because
PKC activity appears to be related to the persistence of LTP and not to the
initial change, we concluded that PKC regulates a post-initiation component
of LTP. To define the time domain in which PKC activation is necessary for
LTP, we studied the effect of the PKC inhibitors polymyxin B (PMXB) and
1-(5- isoquinolinesulfonyl)-2-methylpiperazine (H-7) micropressure ejected
at different time points before and after the induction of LTP. LTP was
produced in intact rats with HFS of the perforant path, and inhibitor
ejections were made in the molecular layer of the dentate gyrus. PMXB,
which at lower doses is a selective inhibitor of PKC, had no effect on
initial potentiation, yet caused decay of the potentiated response to
baseline within 2 hr. Decay occurred when PMXB was ejected 15 min before
and 15 and 30 min after HFS. PMXB, at either low or high doses, was
ineffective in blocking LTP persistence at time points greater than 30 min
after HFS. Low doses of H-7 produced similar effects to those of PMXB.
However, in contrast to a high dose of PMXB, a high dose of H-7 inhibited
the persistence of LTP when delivered 240 min after HFS.(ABSTRACT TRUNCATED
AT 250 WORDS)
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