Biology subjects

Schnepel, P.

Publications and source records attributed to Schnepel, P..

3 recordsLinked to original sources

bioRxiv2024

Control of spatiotemporal activation of organ-specific fibers in the vagus nerve by intermittent interferential current stimulation

Vagus nerve stimulation (VNS) is emerging as potential treatment for several chronic diseases, however, limited control of fiber activation to promote desired effects over side effects restricts clinical translation. Here we describe a new VNS method that relies on intermittent, interferential sinusoidal current stimulation (i2CS) through implanted, multi-contact epineural cuffs. In swine, i2CS elicits specific nerve potentials and end organ responses, distinct from equivalent non-interferential sinusoidal stimulation. Comparing experimental results with anatomical trajectories of nerve fascicles from end organs to the stimulation electrode indicates that i2CS activates organ-specific fascicles rather than the entire nerve. Experimental results and anatomically realistic, physiologically validated biophysical models of the vagus nerve demonstrate that i2CS reduces fiber activation at the focus of interference. Current steering and repetition frequency determine spatiotemporal pattern of vagal fiber activation, allowing tunable and precise control of neural and organ responses. In experiments in a cohort of anesthetized swine, i2CS has improved selectivity for a desired effect, mediated by smaller bronchopulmonary fibers, over a side effect, mediated by larger laryngeal fibers, compared to non-interferential sinusoidal or square pulse VNS.

neuroscience↗

bioRxiv2023

Cortical cellular encoding of thermotactile integration

Recent evidence suggests that primary sensory cortical regions play a role in the integration of information from multiple sensory modalities. How primary cortical neurons integrate multisensory information is unclear, partly because multisensory interactions in the cortex are typically weak or modulatory. To address this question, we take advantage of the robust representation of thermal (cooling) and tactile stimuli in mouse forepaw primary somatosensory cortex (fS1). Using a thermotactile detection task, we show that the perception of threshold level cool or tactile information is enhanced when they are presented simultaneously compared to presentation alone. To investigate the cortical correlates of thermotactile integration, we performed in vivo extracellular recordings from fS1 during unimodal and bimodal stimulation of the forepaw. Unimodal stimulation evoked thermal- or tactile- specific excitatory and inhibitory responses of fS1 neurons. The most prominent features of bimodal, thermotactile stimulation are the recruitment of unimodally silent fS1 neurons, non-linear integration features and a change in the response dynamics to favor longer response durations. Together, we identify quantitative and qualitative changes in cortical encoding that may underlie the improvement in perception of multisensory, thermotactile surfaces during haptic exploration.

neuroscience↗

bioRxiv2018

Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models.

Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide the first systematic test of this hypothesis across 4 mouse models (Fmr1-/y, Cntnap2-/-, 16p11.2del/+, Tsc2+/-), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reductions in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization and spontaneous spiking were essentially normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo, despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype, but appears to reflect homeostatic stabilization of synaptic drive, rather than driving network hyperexcitability in autism.

neuroscience↗