Fig. 1: Dissociation between functional and structural plasticity during mGluR-LTD. | Molecular Psychiatry

Fig. 1: Dissociation between functional and structural plasticity during mGluR-LTD.

From: Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice

Fig. 1

a Extracellular field recordings and time-lapse two-photon imaging were simultaneously performed in the CA1 region of acute Thy1-GFP mouse hippocampal slices with CA3 removed to ensure that agonists acted specifically on receptors on CA1 neurons. b Two-photon image of CA1 pyramidal neurons. SO: Stratum Oriens; SP: Stratum Pyramidale; SR: Stratum Radiatum. c Magnified image of the red-squared region in b showing SR proximal dendrites with dendritic spines. d–g Time-course of averaged fEPSP slope responses (A) and averaged dendritic spine volume (B) normalized to baseline (dashed lines). Representative fEPSP traces and images of dendritic spines are shown at 3 time points: 15 min before, 15 and 60 min after LTD induction. Sequential experiments (gA, B) include two more time points: 90 min and 135 min after induction. Scale bars apply to all panels. Yellow arrows indicate unaltered spines, orange arrows indicate shrinking spines. dA Bath application of vehicle (aCSF, 5 min, gray bars) to hippocampal slices did not alter fEPSP slope (10 min period immediately before vehicle: 102.38 ± 1.81% of total baseline; 50–60 min period after vehicle: 99.40 ± 7.41% of total baseline, n = 10 animals; n.s. p = 0.6635, paired t-test). dB Vehicle did not induce any persistent structural change in spine volume (before: 99.50 ± 0.48%; after vehicle: 99.70 ± 1.71%, n = 10; n.s. p = 0.9077, paired t-test). eA Bath application of NMDA (20 µM, 3 min, magenta bar) induced LTD of fEPSPs (10 min period immediately before NMDA: 99.88 ± 1.65% of total baseline; 50–60 min period after NMDA: 31.78 ± 5.53% of total baseline, n = 9 animals; ****p < 0.0001, paired t-test). eB NMDA induced a long-term decrease in the volume of spines (before: 99.51 ± 0.68%; after NMDA: 83.72 ± 5.29%, n = 9; *p = 0.0235, paired t-test). fA A Bath application of the mGluR agonist DHPG (50 µM, 5 min, blue bar) induced LTD of fEPSPs (before: 99.39 ± 0.76%; after DHPG: 65.3 0 ± 3.35%, n = 16; ***p < 0.0001, paired t-test). fB DHPG did not induce any persistent change in spine volume (before: 100.40 ± 0.52%; after DHPG: 100.30 ± 2.46%, n = 14; n.s. p = 0.9687, paired t-test). Sequential induction of mGluR-LTD and NMDAR-LTD. gA Application of DHPG followed by NMDA induced additional LTD (n = 8; before: 99.85 ± 1.28%; after DHPG: 65.62 ± 5.28%, ***p = 0.005, paired t-test; before NMDA: 65.62 ± 5.28% (lower dashed line); after NMDA: 39.96 ± 7.37% of initial baseline; **p = 0.0022 with respect to before-NMDA, paired t-test). gB DHPG application did not change spine volume (before: 101.10 ± 1.10%; after DHPG: 97.78 ± 1.90%; n.s. p = 0.128, paired t-test) but subsequent NMDA application elicited a robust long-term spine shrinkage in the same population of spines (before: 97.78 ± 1.90%; after NMDA: 68.94 ± 6.57%; ***p = 0.00066, paired t-test). This subsequent spine shrinkage (volume decreased by 32.47 ± 6.0%) tended to be more pronounced than the spine shrinkage caused by the single NMDA application (eB), but this difference did not achieve statistical significance.

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