Fig. 2: Spatial transcriptomics reveals Pmch as a key player in plasticity response.
a,b, Spatial transcriptomics performed on mouse sections of Wt and AppNL-G-F brains at 3.5 MO. a, TDs from CA1 pyramidal layer (p) (b) cluster away from dendritic (d) TDs in an unbiased cluster analysis. Number of TDs in p: Wt n = 33, AppNL-G-F n = 42. c, Results of GO enrichment analysis on the top 200 DE genes (based on P value). GO categories were sorted by P value and the top 8 GO categories were ordered by normalized enrichment score (Fisher’s exact test). The five most enriched GO categories are shown in the bar plot. Coloring represents false discovery rate (FDR). See additional information in Supplementary Table 2. d, Volcano plot showing average gene expression differences between AppNL-G-F and Wt TDs. Significant genes (EdgeR’s quasi-likelihood F test with Benjamini–Hochberg correction < 0.05), are shown in dark gray. Significant genes annotated in SynGO are highlighted in blue, other significant genes of interest are shown in green. The 21 genes annotated in SynGO and present in at least one homeostatic plasticity dataset are labeled (Supplementary Table 3). NS, not significant. e, CA1 pyramidal layer crops showing Pmch, Mchr1 and Vglut1 (Slc17a7) mRNA expression using RNAscope. DAPI was used to label nuclei. Wt n = 2 independent experiments. f,g, Whole-brain coronal section showing expression of Pmch (f) and MCH (g). Wt n = 3 independent experiments. h, Crops of LHA and CA1 regions showing MCH-positive cell bodies in the LHA and axons projecting to CA1 region. Wt n = 3 independent experiments. FC, fold change.
