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Fig. 3 | Alzheimer's Research & Therapy

Fig. 3

From: Activation of PLCβ1 enhances endocannabinoid mobilization to restore hippocampal spike-timing-dependent potentiation and contextual fear memory impaired by Alzheimer’s amyloidosis

Fig. 3

m-3M3FBS restores spike-timing-dependent potentiation (tLTP) impaired by AβO. a Experimental schematic. Whole-cell current-clamp recordings in CA1 pyramidal cells (PCs) and Schaffer collateral (SC) stimulation for tLTP induction at CA3-CA1 excitatory synapses in rat hippocampal slices in vitro. b tLTP induction paradigm consisting of S-eCB mobilization protocol with SC stimulation-evoked presynaptic CA3 PC spikes (SC stim, top) 10 ms before postsynaptic CA1 PC spikes (spikes, middle), repeated 200 times at 1 Hz with DHPG (50 μM) application (bottom). Boxed inset: enlarged presynaptic SC stim-evoked EPSPs paired with postsynaptic CA1 PC spikes during tLTP induction. cg EPSP slopes normalized to the mean of the 10-min baseline after tLTP in DMSO-treated slices (n = 11, c), in the presence of D-AP5 (50 μM) in DMSO-treated slices (n = 8, d), in the presence of AM251 (3 μM) in DMSO-treated slices (n = 5, e), in AβO-treated slices (n = 11, f), and in the presence of m-3M3FBS (30 μM) in AβO-treated slices (n = 9, g). Filled circles: test pathways, empty circles: control pathways. Inset: representative EPSP traces at indicated time points (1, 2 or 1’, 2’). h The mean of normalized EPSPs slopes from the last 5 min of the test (filled bars) and control pathways (empty bars) in DMSO (black), + D-AP5 in DMSO-treated slices (gray), + AM251 in DMSO-treated slices (dotted), in AβO-treated slices (red), and + m-3M3FBS in AβO-treated slices (magenta). Statistical tests: h Paired Student’s t test for comparison between the test and control pathways within the same group, *p < 0.05, ns: p > 0.05; one-way ANOVA with post hoc Tukey’s test for comparison among the test pathways in five different groups (DMSO vs. + D-AP5 in DMSO, # p < 0.05; DMSO vs. + AM251 in DMSO, † p < 0.05; DMSO vs. AβO, & p < 0.05; DMSO vs. AβO + m-3M3FBS, ns: p > 0.05). Data are represented as mean ± SEM

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