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Early correction of synaptic long-term depression improves abnormal anxiety-like behavior in adult GluN2B-C456Y-mutant mice

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Reduced LFS-LTD but normal mGluR-LTD, HFS-LTP, TBS-LTP, and PSD density and morphology in the Grin2b+/C456Y hippocampus.

(A) Reduced LFS-LTD at SC-CA1 synapses of Grin2b+/C456Y mice (P17–19). n = 9 neurons from 7 mice for WT (75.9% ± 2.4%), and 9 (5) for HT (89.1% ± 2.1%), ***P < 0.001, Student t test. (B) Reduced LFS-LTD in the PrL 1 region of the mPFC in Grin2b+/C456Y mice (P17–20). n = 9 neurons from 5 mice for WT (82.9% ± 2.8%), and 10 (5) for HT (97.3% ± 5.8%), *P < 0.05, Student t test. (C) Normal mGluR-LTD induced by the group I mGluR agonist DHPG (50 μM for 10 minutes) at SC-CA1 synapses of Grin2b+/C456Y mice (P16–20). n = 8 (6) for WT (59.3% ± 5.8%), and 8 (4) for HT (67.6% ± 6.4%), Student t test. (D) Normal HFS-LTP at SC-CA1 synapses of Grin2b+/C456Y mice (P27–33). n = 9 (5) for WT (132.5% ± 6.8%), and 10 (4) for HT (130.0% ± 3.2%), Mann-Whitney test. (E) Normal TBS-LTP at SC-CA1 synapses of Grin2b+/C456Y mice (P28–32). n = 11 (6) for WT (159.4% ± 6.6%), and 9 (4) for HT (148.5% ± 4.9%), Student t test. (F) Normal PSD density and morphology (length, depth, and perforation) in the CA1 region of Grin2b+/C456Y mice (P21). n = 3 mice for WT and HT, Student t test. The numerical data underlying this figure can be found in S3 Data. DHPG, dihydroxyphenylglycine; fEPSP, field excitatory postsynaptic potential; HFS, high-frequency stimulation; HT, heterozygous; LTD, long-term depression; LFS, low-frequency stimulation; LTP, long-term potentiation; mGluR, metabotropic glutamate receptor; mPFC, medial prefrontal cortex; ns, not significant; P, postnatal day; PrL, prelimbic layer; PSD, postsynaptic density; SC-CA1, Schaffer collateral-CA1 pyramidal; TBS, theta burst stimulation; WT, wild type.

Fig 2

doi: https://doi.org/10.1371/journal.pbio.3000717.g002