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. 2019 Nov 21;13(6):1022–1037. doi: 10.1016/j.stemcr.2019.10.012

Figure 5.

Figure 5

The Mature and Functional Integration of Human iNPC-Derived Neurons into Local Synaptic Networks of AD Hippocampus

(A) Top, the GFP+ grafted human cells in dentate gyrus on the coronal brain section of Rag2−/−/5XFAD mouse 6 M p.t. Bottom, Aβ deposits on the same brain section.

(B) The close-ups of GFP+ grafted human cells shown in (A). Arrow heads indicate that the green long fibers of human neurons in the grafts projected into the host neurons. Dashed lines indicate the borders between human cell grafts and host neurons.

(C) Immunofluorescence analysis of Iba1 in hippocampal region loaded with Aβ plaques and in GFP+ human cell grafts. Dashed lines indicate the borders between human cell grafts and host neurons.

(D) Spontaneous APs recorded in some iNPC-derived neurons. Inset, an expanded AP for clarity.

(E) The resting membrane potential (left) and input resistance (right) of human neuronal cells at 6 M p.t.

(F) AP generation in grafted human neuronal cells in response to step current injection.

(G) Percentage of human neuronal cells with one AP, or repetitive AP at 6 M p.t.

(H) The F-I curve of human neuronal cells at 6 M p.t.

(I) The green neurites from grafted iNPC-derived neurons expressing PSD95 and distributing among host hippocampal neurons at 6 M p.t. (top). Double immunofluorescence analysis of SYP and GPHN (bottom). Arrowheads indicate PSD95 dots in GFP+ human neurites. Arrows indicate co-localization of SYP and GPHN dots.

(J) Representative traces from human neuronal cells at 6 M p.t. showing sEPSCs at a holding potential of −70 mV and sIPSCs at 0 mV.

(K) The percentage of grafted human neuronal cells exhibiting sEPSCs and sIPSCs.

(L) Representative light-induced responses of grafted human cells with ChR2 expression in voltage-clamp (top) and current-clamp mode (bottom).

(M) Left, firing pattern of a neighbor host granular cell (GC). Right, light stimulation induced an increase in synaptic inputs in GC recorded in voltage-clamp mode at a holding potential of −70 mV.

Scale bars, 1 mm (A), 50 μm (B), 25 μm (C), and 5 μm (I). Sample size: 3 mice. Numbers of recorded cells (n) were shown on the graphs in (E), (G), and (K). Data are represented as means ± SD in (E) and (H). Related to Figure S4.