Krause corpuscles of the genitalia are vibrotactile sensors required for normal sexual behavior
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Abstract
Krause corpuscles, first discovered in the 1850s, are enigmatic sensory structures with unknown physiological properties and functions found within the genitalia and other mucocutaneous tissues. Here, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of the mouse penis and clitoris and project to a unique sensory terminal region of the spinal cord. Using in vivo electrophysiology and calcium imaging, we found that both Krause corpuscle afferent types are A-fiber rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Optogenetic activation of male Krause corpuscle afferent terminals evoked penile erection, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males as well as reduced sexual receptivity of females. Thus, Krause corpuscles, which are particularly dense in the clitoris, are vibrotactile sensors crucial for normal sexual behavior.
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emerged from axons that occasionally passed through Krause corpuscles (fig. S6).
The identify of the neurons that make up these corpuscles is very interesting! Could you explain more how you excluded other sensory fibers from involvement in these corpuscles? For instance it is not obvious to me that fibers that pass through a corpuscle are not involved in its formation. Some quantification of the location of other sensory neurons in the glans/clitoris and their overlap with Krause corpuscles would be very helpful for me here.
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the structural similarity between mouse andhuman Krause corpuscles
Even though you referenced a few papers that discussed Krause corpuscles in humans, this interpretation is difficult to assert based on the data shown. A direct comparison between the cited work and your work may be helpful in order to include this.
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Heatmaps are normalized equally across the tissue types
It would be helpful to have the scale bar in J show the density counts that correspond to "low" and "high"
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An initial survey of mouse genetic tools revealed that two alleles, TrkBCreERand RetCreER (16, 17), efficiently labeled NF200+ Krause corpuscle neurons with high specificity in both female and male genitalia. TrkBCreER(tamoxifen at P5) labeled dorsal root ganglion (DRG) sensory neuron axons that terminate in nearly all Krause corpuscles of both the clitoris and penis (Fig. 2A, and fig. S2, A and B, and S4A), and it did not label other, non-Krause corpuscle, axonal endings in genital tissue.
This is a really important and useful finding! Sharing the data for the specificity of this genetic strategy and quantification of which other fibers are labeled (and in what proportion) would be helpful
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in vivo calcium imaging experiments using both male and female mice that express GCaMP6 in the TrkB+ or Ret+ DRG sensory neuron populations (Fig. 4F)
An example video of DRG calcium responses to mechanical stimuli would be so cool to see here!
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Tdtamato
Typo: Tdtomato
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We found that direct optogenetic stimulation of the penis (10 Hz, 2 ms pulse for 20 s) of TrkBCreER; AvilFlpo; R26FSF-LSL-ReaChR mice, which express ReaChR in TrkB+ Krause corpuscle afferents, led to erectile responses in 6 out of 10 animals. In contrast, light pulses did not evoke erection when delivered to the penis of control animals lacking opsin (Fig. 5C). Moreover, optical stimulation of the glans penis of mice expressing a faster opsin, CatCh (32), in TrkB+ Krause corpuscle afferents using a higher frequency stimulus (20Hz, 1ms pulse for 20s) led to erectile responses in 5 out of 5 animals tested
What leads to the different physiological responses of optogenetic stimulation between stimulation paradigms and between constructs? How does optogenetic stimulation compare with responses to mechanical stimulation?
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Nevertheless, these findings indicate that optogenetic activation of TrkB+ Krause corpuscle afferents is sufficient to initiate sexual reflexes in male mice.
This finding is very exciting, is it also true for female mice? Is it possible to test the female sexual reflex in mice?
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