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. Author manuscript; available in PMC: 2022 Jan 27.
Published in final edited form as: Cell Rep. 2021 Dec 28;37(13):110182. doi: 10.1016/j.celrep.2021.110182

Figure 3. The trans-entorhinal cortex differentially depends on VPS26b.

Figure 3.

(A) Functional MRI. Cerebral blood volume (CBV) fMRI maps were generated from the whole brain of 3- to 4-month-old Vps26b KO and their control littermates (n = 10 per group) and 12- to 14-month-old Vps26b KO mice and their control littermates (n = 9–10 per group) (top left panel). A voxel-based analysis across the whole brain revealed a significant genotype X age focal defect (voxel-wise p < 0.005; cluster-wise p < 0.05; cluster size >25 voxels) (top right panel), which upon magnification is found to localize to the TEC (bottom left panel) (color bar represents t values of the interaction; PRC, perirhinal cortex; EC, entorhinal cortex, HIP, hippocampus; red arrow indicates the TEC). A region of interest (ROI) analysis of the relative CBV (rCBV) at the TEC between Vps26b WT and Vps26b KO revealed a significant age-dependent worsening of rCBV in the TEC region (in an ANOVA analysis of the genotype × age interaction: F[3,38] = 16.08, p = 0.0003; n = 9–10 animals/genotype) (top right panel).

(B) Electrophysiology. An example of an acute ex vivo brain slice whose precise anatomical coordinates were matched to the neuroimaging defects, illustrating electrode placement (top left panel) (TEC, red arrow; MEC, blue arrow). Mean fEPSP slopes, expressed as the percentage of baseline measured before and after high-frequency stimulation in the TEC (top right panel) and in the MEC (bottom left panel), showed that 12- to 14-month-old Vps26b KO mice, compared with control littermates (n = 6 per group), have LTP defects in the TEC (F(1,14) = 69.2; p < 0.001) but normal LTP in the MEC (F(1,14) = 0.93; p = 0.365) in a repeated-measures ANOVA post hoc Tukey test. Abnormal LTP was also found in the TEC of 18-month-old Vps26b HET mice but not in 18-month-old Vps26a HET mice (Vps26b HET versus WT: F(2,11) = 3.27; p = 0.005; Vps26a HET versus WT: p = 0.42) (post hoc Tukey) (bottom right panel).

(C) By comparing co-registered brain slices of GluA1 immunostainings from 14-month-old Vps26b WT mice (n = 5) (left panel) and Vps26b KO mice (n = 5) (middle panel), a pixel-based analysis (“Vps26b WT versus KO”) showed that Vps26b KO mice have focal TEC reductions in GluA1 immunostaining levels (indicated by the red arrow) (right panel) in a two-sample t test; pixel-wise p < 0.001; color bar represents t values. Scale bar, 500 μm.

See also Figure S5.