Fig 1: Decreased excitatory postsynaptic density levels of IL1RAP in Ptprd-meB+/– mice.a Diagram showing the total proteomic analyses of postsynaptic density (PSD) fractions, synaptic plasma membrane (SPM) fractions, and whole lysates from mice. b–d Volcano plots showing differentially expressed proteins (DEPs; P < 0.05 and |fold-change (FC)| >1.2) in Ptprd-meB+/– PSD, SPM, and whole lysate samples (P63; male; whole brain). (n = 4 mice [WT, HT] for PSD and SPM; 3 [WT, HT] for whole lysate, two-tailed Welch’s t-test). e DAVID analyses of DEPs from Ptprd-meB+/– PSD samples. KEGG Kyoto Encyclopedia of Genes and Genomes, CC cellular component, BP biological process, MF molecular function. (Fisher’s exact test). f, g SynGO analysis of DEPs from Ptprd-meB+/– PSD samples for pre/post-synaptic localization (SynGO: location) and synaptic functions (SynGO: function). h Western-blot validation of decreased IL1RAP protein levels in Il1rap+/– mice (P63; male). i Decreased eEPSCs/eIPSC ratios in DG-GCs in the MEC-DG-GC pathway in Il1rap+/– ventral hippocampus (P56–70; male). (n = 16 neurons from 4 mice [Il1rap+/+], 14, 4 [Il1rap+/–], two-tailed Mann–Whitney test, P = 0.0344). j A model suggesting that presynaptic PTPδ-meB deletion in the MEC decreases PSD levels of IL1RAP in DG-GCs (not DG-INs), thereby selectively decreasing excitatory synaptic density in DG-GCs. Note that whether the same axon provides excitatory synaptic inputs onto DG-GCs and DG-INs remains unknown. k Diagram showing acute Neuroligin-3 (Nlgn3) knockdown by injecting AAV9-U6-shNlgn3-GFP into the ventral DG of mice (P35–40) and measuring eEPSC/eIPSC ratios in MEC-DG-GCs (P56–70). AAV9-U6-shCtrl-GFP, control virus. l Unaltered eEPSC/eIPSC ratios in MEC-DG-GCs in Ptprd-meB+/– mice (P56–70; male) injected with AAV9-U6-shNlgn3-GFP (HT shNlgn3). HT mice injected with AAV9-U6-shCtrl-GFP were used as controls (HT shCtrl). (n = 18, 3 [HT shCtrl], 15, 4 [HT shNlgn3], two-tailed Mann-Whitney test). m Unaltered eEPSC/eIPSC ratios in MEC-DG-GCs in WT mice (P56–70; male) injected with AAV9-U6-shNlgn3-GFP (WT shNlgn3). WT mice injected with AAV9-U6-shCtrl-GFP were used as controls (WT shCtrl). (n = 18, 4 [WT shCtrl], 16, 3 [WT shNlgn3], two-tailed Mann–Whitney test). Data values represent means ± SEM. Significance is indicated as * (<0.05) or ns (not significant). Source data are provided as a Source Data file.