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. 2019 Apr 29;5(3):e330. doi: 10.1212/NXG.0000000000000330

Figure 4. Altered long-term potentiation and reduced hippocampal synapse numbers in Hace1 KO mice as compared with WT controls.

Figure 4

(A) Upper left panel, schematic fEPSP recording configuration from acute hippocampal slices: stimulation (red bolt) of CA3-CA1 Schaffer collaterals (green), the fEPSP extracellular recording electrode in the CA1 region (white cone, ep = extracellular pipette). Synaptic transmission at CA3-CA1 hippocampal synapses is increased in Hace1 KO mice compared with WT littermates. fEPSP slopes were normalized to axonal fiber volleys to account for variations in axonal stimulation efficacy between slice preparations and animals. Analysis was performed over a range of stimulus intensities. Average fEPSP slopes were significantly higher in Hace1 KO slices; mean values ± SEM; WT n = 19 and KO n = 20; *p ≤ 0.05; 2-population Student's t test. (B) Representative traces of fEPSPs in response to CA3-CA1 synapse stimulation obtained from WT (black trace) and Hace1 KO (red trace) mice. Field EPSP (black arrow) recordings were normalized to fiber volleys (gray arrow) to account for varying stimulation efficiencies across experiments and preparations. Time scale of recording is indicated. (C) No significant difference was found between fiber volley amplitudes (mean values ± SEM) between the indicated genotypes; WT n = 19 and KO n = 20. (D) Long-term potentiation (LTP) of synaptic transmission was induced by HFS after a 10-minute baseline recording. fEPSP slopes were normalized to their baseline levels and plotted over time. LTP was reduced in Hace1 KO animals; mean values ± SEM; WT n = 19 and KO n = 18; **p ≤ 0.01; 2-population Student's t test. (E) Representative fEPSP traces illustrating LTP experiments displayed in panel (D). Solid lines represent baseline fEPSPs, and dashed lines represent fEPSPs 30 minutes after LTP induction (Hace1 WT: black, upper panel; Hace1 KO: red, lower panel). (F) Representative 3D composite of z-stacked ×63 magnified (zoom factor of 2) confocal images of hippocampal CA1 pyramidal cell distal dendrites of Hace1+/+;Thy1-GFP and Hace1−/−;Thy1-GFP mice. Uncolored dendritic segments are on the left, synaptic spines are pseudocolored in magenta on the right panels; scale bar is 2.5 μm. Right bar graphs show quantifications of spine numbers; mean values ± SEM; WT n = 3 and KO n = 3; **p ≤ 0.01; unpaired Student's t test. fEPSPs = field excitatory post synaptic potentials; KO = knock out; WT = wild type.