Fig. 4

Hippocampal protein interaction subnetworks for ASD, epilepsy and learning/memory. a ASD subnetwork. ASD candidate genes were mapped onto the hippocampal interactome network to extract a subnetwork including ASD genes and first co-expressed PPI neighbors. b Network betweenness centrality of top 10 genes in ASD subnetwork (X-axis, top 10 genes; Y-axis, betweenness centrality). c EP subnetwork. Epilepsy candidate genes were mapped onto the hippocampal interactome network to extract a subnetwork including epilepsy genes and first co-expressed PPI neighbors. d Network betweenness centrality of top 10 genes in EP subnetwork (X-axis, top 10 genes; Y-axis, betweenness centrality). e LM subnetwork. Learning/memory (LM)-related genes were mapped onto the hippocampal interactome network to extract a subnetwork including LM-related genes and first co-expressed PPI neighbors. f Network betweenness centrality of top 10 genes in LM subnetwork (X-axis, top 10 genes; Y-axis, betweenness centrality). g Venn diagram of nodes in subnetworks. h The module of nodes shared by all three subnetworks. i Co-immunoprecipitation was performed on hippocampal tissue lysates from 8-week mice to detect interactions between endogenous protein pairs: GluN1 and GluN2B, GluN1 and PSEN1. Mouse IgG antibody was used as control in the pull down experiments. j Sample traces (left) and summary bar graph (right) of measurements of the ratio of NMDA receptor-mediated versus AMPA receptor-mediated synaptic responses recorded in slices; the NMDA/AMPA current ratio was determined by sequentially evaluating EPSC amplitudes at − 70 mV (AMPA) and at + 40 mV (NMDA) holding potential; NMDA receptor-mediated responses were measured with the mean response between 110 and 160 ms post-stimulus. All data presented as mean ± SEM; n = 15 for WT cells from five mice and n = 14 for Gabra4^−/− cells from five mice; *p < 0.05, Student’s t test