Biology subjects

de Thomas Wagner, D.

Publications and source records attributed to de Thomas Wagner, D..

3 recordsLinked to original sources

bioRxiv2024

Lamellar Schwann cells in the Pacinian corpuscle potentiate vibration perception

Pacinian corpuscles are among the most sensitive mechanoreceptors found in vertebrates and they are tuned to vibrations in the highest perceptible frequency range (100-2000Hz). One of their anatomical hallmarks is the onion-like cell layers surrounding the central axon. The innermost layers consist of [~]60 densely packed lamellar Schwann cells (LSCs), whose function remains largely unknown. Using high-resolution 3D electron microscopy we found that LSCs in Pacinian corpuscles of the mouse hindlimb do not form concentric rings, but complex, multilayered and intertwining assemblies that are connected via an estimated 5805.1 desmosomes and 4142.5 gap-junctions. LSCs make multiple converging contacts with the afferent axon and its protrusions with desmosomes. Using optogenetic manipulations of LSCs we demonstrate that their activation does not only drive reliable time-locked spiking in the axon, but that their inactivation significantly elevates the thresholds in-situ and increases perceptual thresholds behaviorally. Together these findings provide evidence that LSCs are a key element of somatosensory processing, actively potentiating mechanosensitivity in Pacinian corpuscles. HighlightsO_LIHigh-resolution electron microscopy reveals details of the Pacinian corpuscle C_LIO_LILamellar Schwann cells form claw-like structures with converging axonal contacts C_LIO_LISchwann-cell modulation bidirectionally affects neural coding of Pacinian afferent C_LIO_LIInactivation of lamellar Schwann-cells increases perceptual thresholds C_LI

neuroscience↗

bioRxiv2023

Transformation of neural coding for vibrotactile stimuli along the ascending somatosensory pathway

Perceiving substrate vibrations is a fundamental component of somatosensation. In mammals, action potentials fired by rapidly adapting mechanosensitive afferents are known to reliably time lock to the cycles of a vibration. This stands in contrast to coding in the higher-order somatosensory cortices, where neurons generally encode vibrations in their firing rates, which are tuned to a preferred vibration frequency. How and where along the ascending neuraxis is the peripheral afferent temporal code of cyclically entrained action potentials transformed into a rate code is currently not clear. To answer this question, we probed the encoding of vibrotactile stimuli with electrophysiological recordings along major stages of the ascending somatosensory pathway in mice. Recordings from individual primary sensory neurons in lightly anesthetized mice revealed that rapidly adapting mechanosensitive afferents innervating Pacinian corpuscles display phase-locked spiking for vibrations up to 2000 Hz. This precise temporal code was reliably preserved through the brainstem dorsal column nuclei. The main transformation step was identified at the level of the thalamus, where we observed a significant loss of phase-locked spike timing information accompanied by a further narrowing of tuning curve widths. Using optogenetic manipulation of thalamic inhibitory circuits, we found that parvalbumin-positive interneurons in thalamic reticular nucleus participate in sharpening frequency selectivity and disrupting the precise spike timing of ascending neural signals encoding vibrotactile stimuli. To test the functional implications of these different neural coding mechanisms, we applied frequency-specific microstimulation within the brainstem, which generated frequency selectivity reminiscent of real vibration responses in the somatosensory cortex, whereas microstimulation within thalamus did not. Finally, we applied microstimulation in the brainstem of behaving mice and demonstrated that frequency-specific stimulation could provide informative and robust signals for learning. Taken together, these findings not only reveal novel features of the computational circuits underlying vibrotactile sensation, but could also guide biomimetic stimulus strategies to activate specific nuclei along the ascending somatosensory pathway for sensory neural prostheses.

neuroscience↗

bioRxiv2023

Emergence of a somatosensory tonotopic map for substrate vibration in the brainstem

Perceiving substrate vibrations is a fundamental component of tactile perception. The wide frequency spectrum of vibrations is covered by integrating responses of multiple mechanoreceptors that innervate various subtypes of mechanosensitive end organs, each preferring a specific range: Merkel cells (0.5-10Hz), Meissner corpuscles (10-150Hz) and Pacinian corpuscles (150-1000Hz) in primates. As the density of different end organs greatly varies across the body, each body part potentially has a specific frequency preference. How location (somatotopy) and frequency tuning (tonotopy) are processed along the ascending neuraxis and how they converge to drive responses of individual neurons is poorly understood. In this study, we address this question by combining in vivo peripheral electrophysiology and two-photon calcium imaging along the entire dorsal column-medial lemniscal pathway, including the dorsal root ganglia, dorsal column nuclei (DCN), the thalamus and the cortex. Surprisingly, we found that both frequency, as well as location, are organised into structured maps in the DCN. Furthermore, both maps are intimately related at the fine spatial scale with parallel map gradients that are consistent across the depth of the DCN and preserved along the ascending pathway. Additional sensory mapping experiments based on peripheral characterisation revealed that the tonotopic map only partially reflects the distribution of end organs in the skin and deep tissue. Instead, we show that the emergence of the finescale tonotopy is probably due to the selective dendritic sampling from axonal afferents, right at the first synaptic relay. Taken together, we conclude DCN neural circuits are key to the emergence of these two fine-scale topological organisations in early somatosensory pathways. The underlying computational principle is intriguingly similar to the integration of multiple functional maps along the ascending visual pathways, suggesting a universal law governing the optimization of sensory systems.

neuroscience↗