Biology subjects

Saab, C. Y.

Publications and source records attributed to Saab, C. Y..

5 recordsLinked to original sources

bioRxiv2026

Automated detection of blink reflexes evoked by optogenetic stimulation of TRPV1-expressing corneal nociceptors in transgenic mice

BackgroundConventional rodent models for the study of corneal pain commonly evoke eye blink reflex using methods that indiscriminately activate polymodal nociceptors, mechanoreceptors, and thermoreceptors at temporal resolutions that dont closely match the sub-second timescale of underlying neural dynamics. New methodWe introduce a novel automated behavioral paradigm for detecting blink reflexes in transgenic TRPV1-ChR2-EYFP mice, enabled by cell-type-specific, millisecond-precision optogenetic stimulation of corneal nociceptors (490 nm light). Using multi-feature quantification, we achieve robust automated detection using univariate and multivariate classifiers. ResultsTRPV1-ChR2-EYFP mice exhibited blink reflexes to high-intensity blue light (490 nm, 10 ms pulses) in a threshold-dependent manner (N=3). Blink probability was 77.1 {+/-} 17.1% at high intensity (2.77 mW/mm2) versus 4.2 {+/-} 4.2% at low intensity (0.46 mW/mm2). Red light (638 nm) produced no intensity-dependent change. Noxious air puff evoked blinks in >95% of trials under all conditions. DeepLabCut-based pose estimation extracted six features quantifying the blink reflex, enabling automated detection with [≥]98% accuracy using univariate and multivariate classifiers. Comparison with existing methodsUnlike conventional air puff paradigms, this optogenetic approach enables precise, cell-type-specific stimulation of corneal nociceptors, supporting automated analysis of blink responses at sub-second resolution. ConclusionsThis video tracking behavioral method using machine learning algorithms that accurately classify blink versus no-blink enables high-throughput and observer-independent empirical assessment of blink reflex, suggestive of corneal pain. Moreover, inducing blink reflex in TRPV1-ChR2 mice using high-intensity blue light also demonstrates nociceptive-specific behavioral responses analogous to somatosensory optogenetically-evoked hindpaw pain in the same animal genotype.

neuroscience↗

bioRxiv2023

Transient gamma events delineate somatosensory modality in S1

Gamma band activity localized to the primary somatosensory cortex (S1) in humans and animals is implicated in the higher order neural processing of painful and tactile stimuli. However, it is unclear if gamma band activity differs between these distinct somatosensory modalities. Here, we coupled a novel behavioral approach with chronic extracellular electrophysiology to investigate differences in S1 gamma band activity elicited by noxious and innocuous hind paw stimulation in transgenic mice. Like prior studies, we found that trial-averaged gamma power in S1 increased following both noxious and innocuous stimuli. However, on individual trials, we noticed that evoked gamma band activity was not a continuous oscillatory signal but a series of transient spectral events. Upon further analysis we found that there was a significantly higher incidence of these gamma band events following noxious stimulation than innocuous stimulation. These findings suggest that somatosensory stimuli may be represented by specific features of gamma band activity at the single trial level, which may provide insight to mechanisms underlying acute pain.

neuroscience↗

bioRxiv2023

Spinal Cord Stimulation using time-dynamic pulses achieves faster and longer reversal of allodynia compared to tonic pulses in a rat model of neuropathic pain

Spinal cord stimulation (SCS) utilizing time-dynamic pulses (TDPs) is an emergent field of neuromodulation that continuously and automatically modulates pulse parameters. We previously demonstrated that TDPs delivered for 60 min at sub-paresthesia amplitudes significantly reversed allodynia in a rat model of neuropathic pain. Because we observed these anti-allodynic effects persisted post-cessation, we investigated the extended temporal dynamics of SCS-induced analgesia. We hypothesized that TDPs achieve a longer duration of analgesia than tonic stimulation. Both TDPs and tonic stimulation reversed PWT to near pre-chronificiation levels within 30 minutes. Most TDPs exhibited significantly slower ramp-up slope (analgesia wash-in rates) compared to tonic stimulation (amplitude modulation: 0.16{+/-}0.03 min-1, pulse width modulation: 0.18{+/-}0.05 min-1, stochastic modulation: 0.17{+/-}0.04 min-1, tonic: 0.31{+/-}0.06 min-1). All TDPs showed slower wind-down slopes (analgesia wash-out rates) compared to tonic (-0.29{+/-}0.07 min-1), with pulse width modulation (-0.11{+/-}0.02 min-1) reaching significance. Extending SCS from 60 to 90 minutes revealed all TDPs maintain analgesic efficacy longer than tonic stimulation, which decreased significantly at both 75 and 90 minutes (from 13.8{+/-}0.5 g to 12.3{+/-}0.9 g and to 11.0{+/-}0.5 g, respectively). Although TDPs and tonic stimulation comparably mitigated allodynia, TDPs generally exhibited slower temporal dynamics, suggesting longer-lasting analgesic effects and potentially different mechanisms of action.

neuroscience↗

bioRxiv2021

Distinct neocortical mechanisms underlie human SI responses to median nerve and laser evoked peripheral activation

Magneto- and/or electro-encephalography (M/EEG) are non-invasive clinically-relevant tools that have long been used to measure electromagnetic fields in somatosensory cortex evoked by innocuous and noxious somatosensory stimuli. Two commonly applied stimulation paradigms that produce distinct responses in primary somatosensory cortex (SI) linked to innocuous and noxious sensations are electrical median nerve (MN) stimulation and cutaneous laser-evoked (LE) stimulation to the dorsum of the hand, respectively. Despite their prevalence, the physiological mechanisms that produce stereotypic macroscale MN and LE responses have yet to be fully articulated, limiting their utility in understanding brain dynamics associated with non-painful and/or painful somatosensation. Through a literature review, we detailed features of MN and LE responses source-localized to SI that are robust and reproducible across studies. We showed that the first peak in the MN response at [~]20 ms post-stimulus (i.e., MN N1) corresponds to outward-directed deep-to-superficial electrical current flow through the cortical laminae, which is followed by inward-directed current at [~]30 ms (i.e., MN P1). In contrast, the initial LE response occurs later at [~]170 ms (i.e., LE N1) and is oriented inward and opposite the direction of the MN N1. We then examined the neocortical circuit mechanisms contributing to the robust features of each response using the Human Neocortical Neurosolver (HNN) neural modeling software tool (Neymotin et al., 2020). Using HNN as a hypothesis development and testing tool, model results predicted the MN response can be simulated with a sequence of layer specific thalamocortical and cortico-cortical synaptic drive similar to that previously reported for tactile evoked responses (Jones et al., 2007; Neymotin et al., 2020), with the novel discovery that an early excitatory input to supragranular layers at [~]30 ms is an essential mechanism contributing to the inward current flow of the MN P1. Model results further predicted that the initial [~]170 ms inward current flow of the LE N1 was generated by a burst of repetitive gamma-frequency ([~]40 Hz) excitatory synaptic drive to supragranular layers, consistent with prior reports of LE gamma-frequency activity. These results make novel and detailed multiscale predictions about the dynamic laminar circuit mechanisms underlying temporal and spectral features of MN and LE responses in SI and can guide further investigations in follow-up studies. Ultimately, these findings may help with the development of targeted therapeutics for pathological somatosensation, such as somatic sensitivity and acute neuropathic pain.

neuroscience↗

bioRxiv2019

Automated and rapid self-report of nociception in transgenic mice.

A time-resolved, conscious report of detected nociceptive stimuli in mice offers an opportunity to examine the relationship between higher order neural circuits and pain perception. We have developed a detection behavior in transgenic mice that leverages temporally precise and cell-specific stimulation to elicit self-reports of nociception. Conscious reporting of peripheral nociceptive input may help identify neural mechanisms that generate pain perception.

animal behavior and cognition↗