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Dedek, C.

Publications and source records attributed to Dedek, C..

3 recordsLinked to original sources

Encoding of vibrotactile stimuli by mechanoreceptors in rodent glabrous skin

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in rodent glabrous skin has received scant attention, unlike in primates where glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability) whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in rats and mice, we measured the reliability and precision of LTMR responses to different tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting (SA) based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RAI and RAII afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models (GLMs) to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that co-activation patterns play a greater role in population coding than for dichotomously tuned primates RAs. Significance StatementOur sense of touch starts with activation of nerve fibres in the skin. Although response properties of various fibre types are well-established in other species (e.g. primates), quantitative characterization in rats and mice is limited. To fill this gap, we performed a comprehensive electrophysiological investigation into the coding properties of tactile fibres in rodent non-hairy skin and then simulated these fibres to explain differences in their responses. We show that rodent tactile fibres resemble those from other species, but that their heterogeneity at the population level may differ, with potentially important implications for encoding of touch. Simulations reveal intrinsic mechanisms that support this heterogeneity and provide a useful tool to explore somatosensation in rodents.

neuroscience↗

Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain processing neurons across sex in rats and humans

Excitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of NMDAR synaptic responses are conserved between males and females as well as from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain-processing neurons of adult Sprague Dawley rats and human organ donors, including both sexes. By combining patch-clamp recordings of outward miniature excitatory postsynaptic currents with non-biased data analyses, we uncovered a wide range of decay constants of excitatory synaptic events within individual lamina I neurons. Decay constants of quantal synaptic responses were distributed in a continuum from 1-20 ms to greater than 1000 ms, suggesting that individual lamina I neurons contain AMPA receptor (AMPAR)-only as well as GluN2A-, GluN2B-, and GluN2D-NMDAR-dominated synaptic events. This intraneuronal heterogeneity in AMPAR- and NMDAR-mediated decay kinetics was observed across sex and species. However, we discovered a decreased relative contribution of GluN2B-dominated NMDAR responses as well as larger amplitude GluN2D-like events at human lamina I synapses compared to rodent synapses, suggesting species differences relevant to NMDAR subunit-targeting therapeutic approaches. The conserved heterogeneity in decay rates of excitatory synaptic events within individual lamina I pain-processing neurons may enable synapse-specific forms of plasticity and sensory integration within dorsal horn nociceptive networks.

neuroscience↗

Reproducible and fully automated testing of nocifensive behavior in mice

Pain in rodents is often inferred from their withdrawal to noxious stimulation, using the threshold stimulus intensity or response latency to quantify pain sensitivity. This usually involves applying stimuli by hand and measuring responses by eye, which limits reproducibility and throughput to the detriment of preclinical pain research. Here, we describe a device that standardizes and automates pain testing by providing computer-controlled aiming, stimulation, and response measurement. Optogenetic and thermal stimuli are applied to the hind paw using blue and infrared light, respectively. Red light delivered through the same light path assists with aiming, and changes in its reflectance off the paw are used to measure paw withdrawal latency with millisecond precision at a fraction of the cost and data processing associated with high-speed video. Using standard video, aiming was automated by training a neural network to recognize the paws and move the stimulator using motorized linear actuators. Real-time data processing allows for closed-loop control of stimulus initiation and termination. We show that stimuli delivered with this device are significantly less variable than hand-delivered stimuli, and that reducing stimulus variability is crucial for resolving stimulus-dependent variations in withdrawal. Slower stimulus waveforms whose stable delivery is made possible with this device reveal details not evident with typical photostimulus pulses. Moreover, the substage video reveals a wealth of "spontaneous" behaviors occurring before and after stimulation that can considered alongside withdrawal metrics to better assess the pain experience. Automation allows comprehensive testing to be standardized and carried out efficiently.

animal behavior and cognition↗