Biology subjects

Mahrous, A. A.

Publications and source records attributed to Mahrous, A. A..

3 recordsLinked to original sources

bioRxiv2025

Loss of 5-HT2C Receptor Function Alters Motor Behavior and 5-HT2A Receptor Expression in Uninjured and Spinal Cord Injured Mice

The 5-HT2C receptor is involved in the regulation of spinal motor function, specifically in both volitional and involuntary motor behavior. It contributes to various aspects of voluntary movement, such as locomotion, gait, coordination, and muscle contraction, as well as to involuntary motor behavior like spasms, which affect many individuals with spinal cord injury. Despite its known involvement in motor function, little is known about the physiological role of the 5-HT2C receptor and the changes it undergoes after spinal cord injury. In this study, we have investigated the volitional and involuntary motor behavior of male and female uninjured and spinal cord injured knock-out mice that lack the functional 5-HT2C receptor by comparing these genetically manipulated mice to typical-functioning sex-matched wildtype mice. Behavioral assessments revealed differences in volitional muscle strength and coordination, as well as hyperreflexia, between the groups observed. Additionally, ex vivo sacral cord preparation data suggest that 5-HT2C receptor knock-out mice exhibit less spasm-like activity than wildtype mice, corroborating our results from behavioral testing in which the flexor withdrawal reflex of the hindlimbs was assessed. To investigate potential compensatory changes in 5-HT2C receptor expression following spinal cord injury, western blot analysis was performed on lumbar and sacral spinal cord tissue from wildtype and 5-HT2C receptor knock-out mice before and after injury. Both sex and injury status significantly influenced 5-HT2C receptor relative expression and distribution of these receptors in both spinal cord regions. Through a comprehensive approach combining behavioral assessments, electrophysiological experiments, and whole-tissue protein analysis, our findings provide strong evidence that the 5-HT2C receptor plays a critical role in both volitional motor function and involuntary motor behavior, and the relative expression of the 5-HT2C receptor is influenced by both sex and injury status.

neuroscience↗

bioRxiv2024

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.

neuroscience↗

bioRxiv2023

GABA Increases Sensory Transmission In Monkeys

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.

neuroscience↗