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Although simultaneous pairing of presynaptic stimulation and postsynaptic depolarization was originally used for Hebbian LTP of sensorimotor synapses (3), significant LTP of sensorimotor synapses also results from a forward pairing protocol in which the presynaptic stimulation precedes the postsynaptic depolarization by 0.5 s [X. Y. Lin and D. L. Glanzman, J. Neurophysiol. 77, 667 (1997)].
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1842341181
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note
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DL-APV (Sigma, St. Louis, MO) was dissolved in normal ASW to a final concentration of 100 μM and perfused into the recording chamber immediately after Pretest 3. It was washed out immediately after Test 7.
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23
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note
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Summary statistics are presented as mean ± SEM; n denotes number of preparations. Statistical significance for multiple group comparisons was assessed by either parametric or nonparametric [Kruskal-Wallis (KW)] analysis of variance (ANOVA). The choice of statistical test was determined by the outcome of Bartlett's tests for homogeneity of variances performed on the group data. Subsequent between-group comparisons were made with Student-Newman-Keuls tests (parametric) or Dunn's tests (nonparametric). Planned comparisons between two experimental groups were made with either unpaired t tests or nonparametric Mann-Whitney tests. Intragroup comparisons (between pre-and posttests) were made with Wilcoxon signed-rank tests. All reported levels of statistical significance represent two-tailed values.
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note
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The mean amplitude of the Test alone EPSP was 44.2 ± 8% for the 15-min posttest and 43.7 ± 11% for the 60-min posttest. Both of the posttest EPSPs were smaller than the Test alone EPSP on Pretest 3 (P < 0.01 for each comparison). The mean amplitudes of the Test alone-APV EPSP were 61.0 ± 10% for the 15-min posttest and 65.6 ± 7% for the 60-min posttest. Both of these posttest EPSPs were also smaller than the Test alone-APV EPSP on Pretest 3 (P < 0.01 for each comparison).
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25
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note
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+-APV EPSP = 8.4 ± 1.6 mV; Test alone EPSP = 5.4 ± 0.7 mV; Test alone-APV EPSP = 7.1 ± 1.4 mV; F(3,29) = 1.3594, P > 0.2].
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27
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1842315209
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note
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Because there were no significant differences between the Test alone and the Test alone-APV groups in the paired-training experiments (Fig. 1, B and C) (17, 18), we did not include a Test alone-APV group in the unpaired-training experiments.
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The mean EPSP for the Test alone group was 51.0 ± 9% on the 15-min posttest and 75.3 ± 18% on the 60-min posttest. The Test alone EPSP was smaller on the 15-min posttest than on Pretest 3 (P < 0.04). The difference between the EPSPs for Pretest 3 and the 60-min posttest was not significant (P > 0.1).
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39
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1842401571
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--APV EPSP = 4.0 ± 0.9 mV; Test alone EPSP = 4.4 ± 1.2 mV; F(2,28) = 0.2094, P > 0.81).
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40
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1842344054
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Data not shown
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Data not shown.
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0031021083
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+-APV = 35.2 ± 1.4 mV · s). For subsequent pairings (Pairings 2 to 5) the presence of APV produced a slight increase - not a decrease - in the amount of US-induced postsynaptic depolarization. The mean area under the postsynaptic membrane potential during the US, summed across all five pairings, did not differ statistically between the two groups (P > 0.6). These data further argue that our findings cannot be attributed to a nonspecific effect of APV. Consistent with the apparent specificity of the disruptive effect of APV in our experiments is a recent report [S. Schacher, F. Wu, Z.-Y. Sun, J. Neurosci. 17, 597 (1997)] that APV blocks an associative form of long-term enhancement of in vitro sensorimotor synapses but does not affect sensitization-related long-term enhancement of these synapses.
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note
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- EPSP on the 60-min posttest (P < 0.01). The Test alone data in Fig. 2D represent the combined Test alone data from Figs. 1C and 2C. The mean Test alone EPSP for the combined data in Fig. 2D was 47.8 ± 6% for the 15-min posttest and 60.7 ± 11% for the 60-min posttest.
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note
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The time course of the associative effect differed from that described by Hawkins et al. (12), who found that paired training yielded significantly more enhancement than unpaired training 5 to 15 min after training. Several procedural differences between the two studies might account for this difference. First, the duration and intensity of the CS and US in our study differed from those in the study by Hawkins et al. Second, Hawkins et al. used a differential conditioning paradigm in which paired and unpaired training were performed on the same preparations. Nevertheless, our 60-min posttest results substantially resemble the posttest results of Hawkins et al. (see their Fig. 1D), which suggests that the training recruited similar underlying cellular mechanisms in the two studies.
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We thank M. Barish, M. Fanselow, F. Krasne, and T. O'Dell for their helpful comments on the manuscript. Supported by grants from the National Institutes of Health (NS29563), the National Science Foundation (IBN-9410579), the Alzheimer's Disease Program, State of California Department of Health Services (95-23335), and the Academic Senate, University of California, Los Angeles, to D.L.G. as well as by a grant from the National Institute of Mental Health (F31-MH11136) to G.G.M.
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