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Effects of intrahippocampal isoproterenol on fEPSP slope–spike coupling in the dentate gyrus Input–output curves for the 10 levels of stimulation were taken prior to baseline and at the termination of recording (data not shown). The only significant change (P < 0.05) occurred in the 10 μmol/L ISO group in which there was a leftward shift in the input–output relationship. This shift reflected the occurrence of larger Inhibitors,research,lifescience,medical spikes postinfusion for the same stimulation

levels more than 3 h after infusion initiation, a result consistent with the long-term increase in spike size with 10 μmol/L ISO. fEPSP slope/population spike correlations In the majority of granule cells norepinephrine produces a direct increase in membrane resistance Inhibitors,research,lifescience,medical that is mediated by β-adrenoceptors (Lacaille and AG-014699 ic50 Schwartzkroin 1988). We hypothesized that effective β-adrenoceptor activation should increase the EPSP initiation of cell firing. Slope-spike correlations were examined to address this question. There were no significant Inhibitors,research,lifescience,medical correlations between the fEPSP slope and spike size prior to infusion. Immediately after infusion (postinfusion onset 15 min) there was a significant positive correlation (r = 0.76, P < 0.05) in the aCSF group that was not sustained (r = 0.52, ns at 180 min; see

Fig. 3A). In contrast, the 10 μmol/L ISO group exhibited significant positive correlations between EPSP field slope and population spike size at 110 min (r = 0.94, P < 0.005; not shown) and

180 min (r = 0.80, P < 0.05) postinfusion, the last two time points measured (see Fig. 3B). No Inhibitors,research,lifescience,medical other group showed significant correlations between fEPSP slope and population spike size postinfusion. Figure 3 The correlational fEPSP slope and population spike relationship before and after infusion of vehicle (aCSF) or 10 μmol/L ISO. No relationship was found in any group during the preinfusion period (solid line in A and B for examples). (A) ... Discussion Effects of intrahippocampal Inhibitors,research,lifescience,medical ISO infusion on the perforant path-dentate gyrus fEPSP slope The present pattern of results reveals also a β-adrenoceptor-induced long-term depression (LTD) of the perforant path-evoked fEPSP in the dentate gyrus at the lowest level of receptor activation in this study (0.1 μmol/L). A weaker level of depression was also seen with the next higher dose (1 μmol/L). Winson and Dahl (1985) using ISO iontophoresis in the mid-dendritic layer reported depression of the perforant path fEPSP; however, fEPSP depression occurred with all noradrenergic agents applied. In vitro exclusively lateral perforant path activation paired with 1 μmol/L ISO produces a LTD of the fEPSP, while medial perforant path pairing initiates long-term potentiation at the same concentration (Dahl and Sarvey 1990). However, in this study, no attempt was made to isolate lateral perforant path fibers.

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