Fig. 5: Transplanted hCO make functional connections onto rat neurons and modulate behaviour.
From: Maturation and circuit integration of transplanted human cortical organoids
a, Schematic of axon tracing (left). t-hCO EYFP expression (right). Scale bar, 100 μm. A1, auditory cortex; ACC, anterior cingulate cortex; d. striatum, dorsal striatum; HPC, hippocampus; l. septum, lateral septum; mPFC, medial prefrontal cortex; piri, piriform cortex; v. striatum, ventral striatum; VPM, ventral posteromedial nucleus of thalamus; VTA, ventral tegmental area. Red squares indicate the region of the brain from which the image is taken. b, Schematic of the stimulation experiment. c,d, Example blue light-evoked photocurrents (top) and voltage responses (bottom) in human EYFP+ t-hCO (c) or rat EYFP– cells (d). e,f, Current traces from rat neurons following blue light stimulation of t-hCO axons with TTX and 4-AP (green), TTX (grey) or in aCSF (black) (e), or with (purple) or without (black) NBQX (f). g, Latency of blue light-evoked responses in rat cells (n = 16 cells); horizontal bar indicates mean latency (7.13 ms) (left). Amplitude of light-evoked EPSCs recorded with or without NBQX (n = 7 cells; ***P < 0.0001) (middle). Percentage of rat cells that demonstrated EPSCs in response to blue light (right). h, Schematic of the behavioural task. d0, day 0. i, Performance of an example animal on day 1 (left) or day 15 (right) of training. The mean number of licks performed on day 1 (left) or day 15 (right centre) (n = 150 blue light trials, n = 150 red light trials; ***P < 0.0001). Cumulative lick count across red and blue light trials on day 1 (left centre) or day 15 (right). NS, not significant. j,k, Behavioural performance of all animals transplanted with t-hCO expressing hChR2–EYFP (j) or control fluorophore (k) on day 1 or day 15 (hChR2–EYFP: n = 9 rats, **P = 0.0049; control: n = 9, P = 0.1497). l, Evolution of preference score (n = 9 hChR2, n = 9 control; **P < 0.001, ***P < 0.0001). m, FOS expression in response to optogenetic activation of t-hCO in the S1. Images of FOS expression (left), and quantification (n = 3 per group; *P < 0.05, **P < 0.01 and ***P < 0.001) (right) are shown. Scale bar, 100 μm. Data are presented as mean ± s.e.m. BLA, basolateral amygdala; MDT, mediodorsal nucleus of the thalamus; PAG, periaqueductal grey.
