Biology subjects

Iskols, M.

Publications and source records attributed to Iskols, M..

4 recordsLinked to original sources

bioRxiv2023

Activity-dependent development of the body's touch receptors

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end organ structures and altered somatosensory neuron central targeting. Single cell RNA sequencing of Piezo2 conditional mutants revealed changes in gene expression in the sensory neurons activated by light mechanical forces, whereas other neuronal classes were less affected. To further test the role of activity in mechanosensory end organ development, we genetically deleted the voltage-gated sodium channel Nav1.6 (Scn8a) in somatosensory neurons throughout development and found that Scn8a mutants also have disrupted somatosensory neuron morphologies and altered electrophysiological responses to mechanical stimuli. Together, these findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of the mechanosensory end organs that underlie our sense of gentle touch.

neuroscience↗

bioRxiv2023

Krause corpuscles of the genitalia are vibrotactile sensors required for normal sexual behavior

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.

neuroscience↗

bioRxiv2023

A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes

Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes 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.

neuroscience↗

bioRxiv2023

Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch

Specialized mechanosensory end organs within mammalian skin--hair follicle-associated lanceolate complexes, Meissner corpuscles, and Pacinian corpuscles--enable our perception of light, dynamic touch1. In each of these end organs, fast-conducting mechanically sensitive neurons, called A{beta} low-threshold mechanoreceptors (A{beta} LTMRs), associate with resident glial cells, known as terminal Schwann cells (TSCs) or lamellar cells, to form complex axon ending structures. Lanceolate-forming and corpuscle-innervating A{beta} LTMRs share a low threshold for mechanical activation, a rapidly adapting (RA) response to force indentation, and high sensitivity to dynamic stimuli1-6. How mechanical stimuli lead to activation of the requisite mechanotransduction channel Piezo27-15 and A{beta} RA-LTMR excitation across the morphologically dissimilar mechanosensory end organ structures is not understood. Here, we report the precise subcellular distribution of Piezo2 and high-resolution, isotropic 3D reconstructions of all three end organs formed by A{beta} RA-LTMRs determined by large volume enhanced Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) imaging. We found that within each end organ, Piezo2 is enriched along the sensory axon membrane and is minimally or not expressed in TSCs and lamellar cells. We also observed a large number of small cytoplasmic protrusions enriched along the A{beta} RA-LTMR axon terminals associated with hair follicles, Meissner corpuscles, and Pacinian corpuscles. These axon protrusions reside within close proximity to axonal Piezo2, occasionally contain the channel, and often form adherens junctions with nearby non-neuronal cells. Our findings support a unified model for A{beta} RA-LTMR activation in which axon protrusions anchor A{beta} RA-LTMR axon terminals to specialized end organ cells, enabling mechanical stimuli to stretch the axon in hundreds to thousands of sites across an individual end organ and leading to activation of proximal Piezo2 channels and excitation of the neuron.

neuroscience↗