Biology subjects

Lehnert, B. P.

Publications and source records attributed to Lehnert, B. P..

4 recordsLinked to original sources

bioRxiv2025

Fast-conducting mechanonociceptors uniquely engage reflexive and affective pain circuitry to drive protective responses

Nociceptors detect damaging stimuli and evoke pain in healthy animals. We conducted an optogenetic activation screen to identify genetically defined nociceptor populations that elicit place aversion and nocifensive behaviors in response to stimulation. Smr2Cre- and Bmpr1bCre-labeled A{delta} high-threshold mechanoreceptors (HTMRs) emerged as two of the few nociceptor populations, and we focused on investigating their physiological, morphological, functional, and synaptic properties. These neurons densely innervate skin and other organs, are activated only by intense, potentially damaging stimuli, and are necessary for protective responses to sharp mechanical stimuli. Centrally, A{delta}-HTMRs projections span multiple spinal segments and terminate across spinal cord laminae, forming strong, monosynaptic connections onto anterolateral tract projection neurons, including antenna cells of the deep dorsal horn. A{delta}-HTMRs also engage a local spinal reflex circuit enabling a remarkably rapid limb withdrawal. Thus, A{delta}-HTMRs are myelinated nociceptors with unique properties that can be exploited for development of new analgesics.

neuroscience↗

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↗

bioRxiv2022

The encoding of touch by somatotopically aligned dorsal column subdivisions

The somatosensory system decodes a range of tactile stimuli to generate a coherent sense of touch. Discriminative touch of the body depends on signals conveyed from peripheral mechanoreceptors to the brain via the spinal cord dorsal column and its brainstem target the dorsal column nuclei (DCN)1, 2. Models of somatosensation emphasize that fast-conducting low- threshold mechanoreceptors (LTMRs) innervating the skin drive the DCN3, 4. However, post- synaptic dorsal column neurons (PSDCs) within the spinal cord dorsal horn also collect mechanoreceptor signals and form a second major input to the DCN5-7. The significance of PSDCs and their contributions to the coding of touch have remained unclear since their discovery. Here, we show that direct LTMR inputs to the DCN convey vibrotactile stimuli with high temporal precision, whereas PSDCs primarily encode touch onset and the intensity of sustained contact into the high force range. LTMR and PSDC signals topographically re-align in the DCN to preserve precise spatial detail. Different DCN neuron subtypes have specialized responses that are generated by unique combinations of LTMR and PSDC inputs. Thus, LTMR and PSDC subdivisions of the dorsal column encode different tactile features and differentially converge in the DCN to generate unique ascending sensory processing streams.

neuroscience↗

bioRxiv2021

Mechanoreceptor synapses in the brainstem shape the central representation of touch

Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, potentially reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we find that disproportionate representation of glabrous skin emerges over postnatal development at the first synapse between peripheral mechanoreceptors and their central targets in the brainstem. Mechanoreceptor synapses undergo developmental refinement that depends on proximity of their terminals to glabrous skin, such that those innervating glabrous skin make synaptic connections that expand their central representation. In mice that do not sense gentle touch, mechanoreceptors innervating glabrous skin still make more powerful synaptic connections in the brainstem. We propose that the skin region a mechanoreceptor innervates controls refinement of its central synapses over development to shape the representation of touch in the brain.

neuroscience↗