Fig. 4: Functional maturation and synaptic integration of NPC-derived cortical neurons post-transplantation.
a Chemical formula for the synthetic radiotracer 18F-SynVest-1 and a schematic diagram of its microPET scan. b, c Representative cerebral 18F-SynVest-1 PET images (b) and semiquantitative analysis (c) of the SUVr in vehicle and NPC groups (n = 3 rats in vehicle group, n = 3 rats in NPC group; Data are means ± SEM. *P = 0.021, two-way ANOVA followed by Sidak’s post hoc test). Images are shown in coronal view. The white lines depict the midline of the rat brain, while the black circles denote the transplanted regions. TP, transplantation. SUVr = SUV (transplanted region) / SUV (brain stem region). d Gene Ontology (GO) analysis of NPC-derived cell subtypes after transplantation (See also Supplementary Data 2). e Engrafted GFP/gold nanoparticle-positive grafted human neurons (marked in black, dense particles with red arrows) with Golgi apparatus (red arrowheads) and mitochondria (red asterisk). The experiment was independently repeated 6 times in two rats, yielding similar results. Scale bar, 2 μm. f–h Engrafted GFP/gold nanoparticle-positive grafted human neurons (marked in black, dense particles with red arrows) established asymmetric (f) and symmetric (g) synaptic contacts with rat host neurons. Scale bar, 500 nm. h Summary pie chart of proportion of synaptic types (n = 251 synapses from two rats) at 6 weeks after transplantation. i–k Engrafted GFP/gold nanoparticle-positive grafted human neurons (marked in black, dense particles with red arrows) established afferent (i) and efferent (j) synaptic contacts with rat host neurons. Scale bar = 500 nm. k Summary pie chart of proportion of synaptic types (n = 251 synapses from two rats) at 6 weeks after transplantation. l Left: Representative trace of action potential firing pattern of NPC-derived cortical neurons elicited by 50 pA depolarizing current injection. Right: Summary pie chart of proportion of recorded NPC-derived cells firing action potentials (n = 27 cells from a total of 4 rats) at 7 weeks post-transplantation (2 rats) and 11 weeks post-transplantation (2 rats). m Left: Representative traces of spontaneous excitatory (sEPSC) or inhibitory postsynaptic current (sIPSC), which were blocked by glutamate receptor antagonist NBQX (AMPAR antagonist, 5 μM) or GABAA receptor antagonist bicuculine (10 μM), respectively. Right: Summary pie chart of proportion of cells displaying postsynaptic currents (n = 23 cells from a total of 4 rats) at 7 weeks post-transplantation (2 rats) and 11 weeks post-transplantation (2 rats). Source data are provided as a Source Data file.
