Additional file 12 of A Trem2R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques
Creators: name: Tran, Kristine M.
name: Kawauchi, Shimako
name: Kramár, Enikö A.
name: Rezaie, Narges
name: Liang, Heidi Yahan
name: Sakr, Jasmine S.
name: Gomez-Arboledas, Angela
name: Arreola, Miguel A.
name: Cunha, Celia da
name: Phan, Jimmy
name: Wang, Shuling
name: Collins, Sherilyn
name: Walker, Amber
name: Shi, Kai-Xuan
name: Neumann, Jonathan
name: Filimban, Ghassan
name: Shi, Zechuan
name: Milinkeviciute, Giedre
name: Javonillo, Dominic I.
name: Tran, Katelynn
name: Gantuz, Magdalena
name: Forner, Stefania
name: Swarup, Vivek
name: Tenner, Andrea J.
name: LaFerla, Frank M.
name: Wood, Marcelo A.
name: Mortazavi, Ali
name: MacGregor, Grant R.
name: Green, Kim N.
Publisher: name: figshare
Year: 2023
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Neuroscience
subject: Physiology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: 110309 Infectious Diseases

description: Additional file 12: Supplemental Figure 11. Synaptic activity and immunostain. a-c Input-outputcurves measuring the magnitude of the (a) fEPSP slope and (b) fiber volley across a range of stimulation currents (10-100 µA) were comparable in fEPSP slope between 4 mo 5xFAD, Trem2R47H, and WT, but not 4 mo 5xFAD/Trem2R47H (p&lt;0.01). All three experimental groups showed a significant decrease in fiber volley amplitude with respect to WT controls (p &lt;0.0001). c Left, Input-output curve comparing the amplitude of the fiber volley to the slope of the fEPSP response across a range of stimulation currents. Right, the mean slope of the input-output curves for each slice/group was significantly enhanced in slices from Trem2R47H mice relative to WT controls. d Representative super-resolution images at 63X objective of CA1 from 4-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice immunolabeled with Bassoon (BSN) for presynaptic elements (red; top panel) and PSD-95 for postsynaptic elements (green; bottom panel). e-f Quantification of (e) Bassoon+ and (f) PSD-95+ spots per µm3 showed a decrease in both pre- and post-synaptic puncta in 5xFAD and a trending rescue of presynaptic elements in 5xFAD/Trem2R47H mice. g-i Input-output curves measuring the magnitude of the (g) fEPSP slope and (h) fiber volley across a range of stimulation currents (10-100 µA). (g)The fEPSP slopes generated in the latter part of the input-output curve were significantly reduced in slices from 12 mo 5xFAD, Trem2R47H, and 5xFAD/Trem2R47H mice relative to WT controls (p&lt;0.0001). (h) No measurable difference in fiber volley amplitude was found at any given stimulus between groups. i Left, Input-output curve comparing the amplitude of the fiber volley to the slope of the fEPSP response across a range of stimulation currents. Right, the mean slope of the input-output curves for each experimental slice/group was not significantly different from WT controls. j Representative super-resolution images at 63X objective of CA1 from 12-month-old WT, Trem2R47H, 5xFAD, and 5xFAD/Trem2R47H mice immunolabeled with Bassoon for presynaptic elements (red; top panel) and PSD-95 for postsynaptic elements (green; bottom panel). k Bassoon+ pre-synaptic element decreases in 5xFAD mice compared to WT. l PSD-95+ spots per µm3 reveals decrease in post-synaptic puncta in Trem2R47Hcompared to WT mice and an increase in 5xFAD/Trem2R47H compared to 5xFAD mice. n=10-12. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001, ****p&lt;0.0001.