Fig. 4: TrkB⁺ and Ret⁺ Krause corpuscle afferents are fast-conducting, low-threshold mechanical vibration sensors.

a, Schematic of mechanical stimulation of the glans penis during in vivo MEA recording of L6 DRG neurons. The blue object on the opposite side of the indenter stabilizes the glans penis. b, The histogram of spike latency (grey bars) after optogenetic activation (1 ms pulse, blue bar) of a TrkB⁺ Krause corpuscle neuron of the penis. c–e, The optotagged TrkB⁺ neuron in b exhibits robust activation by brushing (c), rapid adaptation to step indentations (d) and phase-locking properties to sinewave vibration stimuli (120 Hz, 19 mN) (e). f, Schematic of in vivo calcium imaging of L6 DRG neurons. Inset: electrical stimulation was applied to the exposed dorsal nerve of clitoris after mechanical stimulation of the clitoris. g,h, Representative calcium signals after step indentations in the clitoris (g) and penis (h). For g and h, scale bars, 5% ΔF/F (vertical) and 5 s (horizontal). All TrkB⁺ neurons (13 in the clitoris, 16 in the penis) and a subset of Ret⁺ neurons (9 out of 18 in the clitoris, 8 out of 10 in the penis) showed an ON–OFF response, while the remaining Ret⁺ neurons showed only an ON response (bottom). i, Comparison of indentation thresholds (log₂ scale) of TrkB⁺ and Ret⁺ Krause afferents. Statistical analysis was performed using two-way ANOVA with Tukey’s multiple-comparison test. j, Representative responses of TrkB⁺ Krause corpuscle afferents to ramping-force vibration stimuli of varying frequencies applied on the penis (top). Left, raster plot of spikes from an optotagged TrkB⁺ neuron across five repeated trials. Right, calcium signals from a TrkB⁺ Krause afferent across three trials. The horizontal dashed lines indicate the criteria of response (5 × s.d. of the baseline); the vertical dashed lines indicate the timing of response onset. k, Normalized frequency turning curves. The mechanical threshold for each vibration frequency is normalized to the minimum threshold of the neuron (individual neurons, grey; average, black). NR, no response. n indicates the number of neurons. For i, data are mean ± s.d. The diagrams in a and f were created by G. Park.

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