Uncovering morphological and functional features of somatosensory neurons innervating hairy skin and genitalia

Abstract

Somatosensory stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG), while different skin types host a diversity of sensory structures with distinct tuning properties and functions. Achieving a holistic view of how this diverse neuronal population relays sensory information from different types of skin to the central nervous system (CNS) has been challenging with existing tools. We used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. In the first part of my thesis, we systematically characterized the morphological and physiological properties of the distinct DRG neuron subtypes innervating hairy skin. Using a newly generated somatosensory neuron genetic toolbox, we performed morphological analysis to reveal the unique cutaneous axon arborization areas and branching patterns of each primary somatosensory neuron subtype. Physiological analysis showed that these subtypes also exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space. In the second part of my thesis, we focused on the specialized sensory structures in the genitalia, known as Krause corpuscles. Although they were discovered in the 1850s, the physiological properties and functions of Krause corpuscles have remained unknown. Utilizing mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed 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. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate distinct female and male mating behaviors.