Fig. 5: Presynaptically located cholinergic receptors mediate TA EPSC reduction at CA1 pyramidal neurons. | Nature Communications

Fig. 5: Presynaptically located cholinergic receptors mediate TA EPSC reduction at CA1 pyramidal neurons.

From: Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Fig. 5

A Schematic illustrating GDP-β-S blockade of GPCR function by inclusion in the recording pipette. B, C GDP-β-S blocks Carbachol (CCh, 10 µM)-induced depolarisation of membrane potential (Vm, left) and reduction of input resistance (Rin, right) (control, n = 21 from 13 mice, GDP-β-S, n = 7 from 3 mice, two-tailed unpaired t-tests, Vm p = 0.025, Rin p = 0.009). D Schematic illustrating pharmacological isolation of EPSCs from TA pathway and example traces showing depression by CCh (10 µM) in the presence of GDP-β-S. E Schematic illustrating the putative role of GABA spillover from neighbouring synapses on presynaptic TA pathway terminals and example traces showing depression of EPSCs by CCh in the presence of GABA receptor antagonists picrotoxin (PTX, 50 µM) and CGP55845 (5 µM). F Schematic illustrating putative action of retrograde endocannabinoids on presynaptic TA pathway terminals and example traces showing depression of EPSCs by CCh in the presence of CB1 receptor antagonist AM251 (1 µM) and GABA receptor antagonist picrotoxin (50 µM). G, H Quantification of EPSC depression by CCh (G CCh, n = 21 from 13 mice, p < 0.0001; CCh + GDP-β-S, n = 7 from 3 mice, p < 0.0001; CCh + PTX + CGP, n = 9 from 4 mice, p < 0.0001; CCh + PTX + AM251, n = 12 from 4 mice, p < 0.0001; CCh vs CCh + GDP-β-S, p = 0.31; CCh vs CCh + PTX + GDP, p = 0.26; CCh vs CCh + PTX + AM251, p = 0.002) and change in PPR (H CCh, n = 21 from 13 mice, p = 0.006; CCh + GDP-β-S, n = 7 from 3 mice, p = 0.047; CCh + PTX + CGP, n = 9 from 4 mice, p = 0.007; CCh + PTX + AM251, n = 12 from 4 mice, p = 0.017; CCh vs CCh + GDP-β-S, p = 0.18; CCh vs CCh + PTX + GDP, p = 0.31; CCh vs CCh + PTX + AM251, p = 0.79; inter-group comparisons one-way ANOVA with post hoc Bonferroni correction. Within-group comparisons two-tailed paired t-test). Data are mean ± SEM; **p < 0.01, *p < 0.05. Source data are provided as a Source Data file.

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