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Abd El Hay, M.

Publications and source records attributed to Abd El Hay, M..

3 recordsLinked to original sources

Central infusion of prostaglandin E2 reveals a unified representation of sickness in the mouse insular cortex

During infections, vertebrates develop stereotypic symptoms such as elevated body temperature, reduced appetite, and lethargy. These changes, collectively known as sickness syndrome, are orchestrated by the brain in response to immune mediators released during systemic inflammation. While the roles of subcortical regions, including the hypothalamus and brainstem nuclei, in regulating sickness symptoms are well established, the contribution of the neocortex to the encoding and modulation of the sick state remains less well understood. We examined the neuronal correlates of sickness in the neocortex of awake mice following a single intracerebroventricular (i.c.v.) injection of prostaglandin E2 (PGE2), a well-characterized mediator of sickness. Behavioral analysis revealed that PGE2 elicited a rapid and robust sickness response, characterized by fever, slower locomotion, quiescence, anorexia, and eye squinting. Whole-brain Fos mapping showed that PGE2 generates a distinct neural activation pattern encompassing much of the interoceptive network. Electrophysiological recordings using Neuropixel probes in awake mice together with dimensionality reduction and decoding analysis revealed that neuronal population dynamics in the insular cortex (IC) and the primary somatosensory cortex (SSp), two regions involved in body state representation, encode sickness-related information, such as body temperature, walking velocity, grooming, and eye squinting. However, unlike SSp, ongoing neuronal activity in IC exhibited a better decoding performance for an integrated measure of sickness rather than individual symptoms. Together, these results suggest that PGE2 induces a coordinated physiological and behavioral response akin to a sick state, which is preferentially encoded in the IC.

neuroscience↗

The DREAM implant: A Lightweight, Modular and Cost-Effective Implant System for Chronic Electrophysiology in Head-fixed and Freely Behaving Mice

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. However, current methods for chronically implanting probes present steep trade-offs between cost, ease of use, size, adaptability and long-term stability. SUMMARYIntroducing a lightweight, cost-effective probe implant system for chronic electrophysiology in rodents, optimized for ease of use, probe recovery, experimental versatility and compatibility with behavior. This protocol introduces a novel chronic probe implant system for mice called the DREAM (Dynamic, Recoverable, Economical, Adaptable and Modular), designed to overcome the trade-offs associated with currently available options. The system provides a lightweight, modular and cost-effective solution with standardized hardware elements that can be combined and implanted in straightforward steps and explanted safely for recovery and multiple re-use of probes, significantly reducing experimental costs. The DREAM implant system integrates three hardware modules: (1) a microdrive that can carry all standard silicon probes, allowing experimenters to adjust recording depth across a travel distance of up to 7mm; (2) a 3D-printable, open-source design for a wearable Faraday cage covered in copper mesh for electrical shielding, impact protection and connector placement, and (3) a miniaturized head-fixation system for improved animal welfare and ease of use. The corresponding surgery protocol was optimized for speed (total duration: 2 hours), probe safety and animal welfare. The resulting implants had minimal impact on animals behavioral repertoire, were easily applicable in freely moving and head-fixed contexts and delivered clearly identifiable spike waveforms and healthy neuronal responses for weeks of data collection post-implant. Infections and other surgery complications were extremely rare. As such, the DREAM implant system is a versatile, cost-effective solution for chronic electrophysiology in mice, enhancing animal well-being, and enabling more ethologically sound experiments. Its design simplifies experimental procedures across various research needs, increasing accessibility of chronic electrophysiology in rodents to a wide range of research labs.

neuroscience↗

HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction

Somatosensation, the detection and transduction of external and internal stimuli, has fascinated scientists for centuries. But still, some of the mechanisms how distinct stimuli are detected and transduced are not entirely understood. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, the accessibility to human pluripotent stem cells and the possibility to generate and study human sensory neurons has enriched the somatosensory research field.\n\nBased on our previous work, the generation of functional human mechanoreceptors, we describe here the generation of hESC-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations. One protocol in particular allowed the generation of a sensory neuron population, homogeneously expressing TRPV1, a prototypical marker for nociceptors. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation.\n\nSurprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.

neuroscience↗