Fig. 5: VC-L5 neurons from 5XFAD mice show reduced intracortical synaptic connectivity during critical period.
A Schematic illustration of a VC slice preparation, LSPS mapping in which different stimulus (laser uncaging) locations relative to recorded V5 neurons lead to direct soma (1), inhibitory (2), or excitatory synaptic (3) currents. B Illustration and digital image of VC slice with registered LSPS mapping grid. LSPS mapping was performed on the L5 pyramidal neuron. A 16 × 16 stimulus grid was centered on bV1 with top row aligned with pia surface. Cyan asterisks indicate glutamate uncaging locations. C LSPS mapping/glutamate uncaging at different locations can elicit direct soma responses, excitatory synaptic responses (EPSC), inhibitory synaptic response (IPSC), or no response. D Representative 10 × 10 mapping traces (corresponding to red square areas in B) of excitatory responses from 5XFAD and WT neurons. Traces contaminated by direct soma responses were removed from display. Triangle indicates soma location. E Representative 10 × 10 mapping traces of inhibitory responses from 5XFAD and WT neurons. F Averaged excitatory connectivity map from WT (n = 13 cells/8 mice) and 5XFAD (n = 11 cells/8 mice) neurons. Averaged strength of synaptic inputs binned by cortical layers are plotted to the right. G 5XFAD neurons show significantly altered laminar inputs (main effect of group, F(1,352) = 5.67, p = 0.018. Two-way ANOVA). H Combined L2/3 inputs from 5XFAD neurons show a significant reduction in connectivity strength (*p = 0.02). I Averaged inhibitory connectivity map from WT (n = 10 cells/8 mice) and 5XFAD (n = 9 cells/7 mice) neurons. Averaged strength of inhibitory synaptic inputs binned by cortical layers are plotted to the right. J 5XFAD neurons show significantly altered laminar inputs (F(1,272) = 171.3, ****p < 0.0001. Two-way ANOVA). K Combined inhibitory inputs from L2/3 and L5 also show a significant reduction in 5XFAD neurons (t17 = 8.6, ****p < 0.0001).
