Biology subjects

Elseedy, H.

Publications and source records attributed to Elseedy, H..

3 recordsLinked to original sources

bioRxiv2026

Chemogenetic activation of hypothalamic oxytocin neurons reorients face exploration toward the eyes in macaques

Oxytocin (OT) shapes social behavior across species. However, in humans and non-human primates, its effects have been studied mainly through exogenous administration, despite uncertainty about the extent to which peripherally administered OT reaches the brain and limited control over the neural pathways it engages. To overcome these limitations, we developed a chemogenetic approach targeting the endogenous OT system by selectively activating OT neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of macaques using excitatory DREADDs. We combined this approach with digit-tracking, a non-invasive, calibration-free assay of face exploration in freely moving animals. In this task, subjects explored blurred face images through a finger-controlled viewing window, providing a proxy for gaze exploration and enabling behavioral assessment of OT neuron activation. DREADD-mediated activation redirected ongoing face exploration toward the eyes at the expense of non-face regions, increasing the consistency of eye-directed exploration and the time spent inspecting the eyes once reached. Immunohistochemical analysis confirmed selective DREADD expression in OT neurons of the PVN and SON. These findings provide the first causal evidence in primates that hypothalamic OT neurons regulate social visual orienting by increasing exploration of the eyes, thereby linking a hallmark effect of intranasal OT administration to defined central OT pathways and establishing chemogenetic access to this system in freely behaving macaques.

neuroscience↗

bioRxiv2026

Sex differences in epigenetic mechanisms of chronic pain-induced depression

Chronic pain is a major risk factor for depression, yet the molecular mechanisms underlying this comorbidity remain poorly understood, particularly in women. To address this gap, we systematically investigated sex differences in the epigenomic adaptations associated with chronic pain-induced depressive-like behaviors. Neuropathic pain was induced in the mouse using the sciatic nerve cuff model, and molecular analyses were performed in the anterior cingulate cortex (ACC), a key brain region implicated in both pain and affective processing. We profiled genome-wide DNA methylation, three histone modifications (H3K27ac, H3K4me1, and H3K27me3), and gene expression using EM-seq, Cut&Tag sequencing, and RNA-seq, respectively. Differential analyses were conducted for each molecular layer and integrated through gene co-expression network analysis. We found that chronic pain induced extensive remodeling of DNA methylation and histone modification landscapes in both sexes. Strikingly, these changes occurred at largely distinct genomic loci in males and females, revealing pronounced sex-specific epigenetic responses. Despite this divergence, the affected regions displayed similar regulatory organization, including enrichment at shared genic features, transcription factor binding sites, and chromatin profiles. Importantly, these adaptations converged on partly overlapping genes, biological pathways, and co-expression modules across sexes. The most affected gene modules were predominantly associated with synapse-related processes, consistent with previous knowledge, and were closely connected to modules enriched for epigenetic regulatory functions. Together, these findings indicate that chronic pain engages sex-specific epigenetic mechanisms that ultimately converge on common functional outcomes. Such convergence highlights the potential value of targeting sex-specific epigenetic substrates in future therapeutic strategies.

neuroscience↗

bioRxiv2019

The GABA-Glutamate supramammillary-dorsal Dentate Gyrus pathway controls theta and gamma oscillations in the DG during paradoxical sleep

Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to fully characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice. At the cellular level, we show that the SuML-DG neurons co-release GABA and glutamate on dentate granule cells and increase the activity of a subset of DG granule cells. At the network level, we show that activation of the SuML-DG pathway increases theta power and frequency during PS as well as gamma power during PS and waking in the DG. At the behavioral level, we show that the activation of this pathway does not change animal behavior during PS, induces awakening during slow wave sleep and increases motor activity during waking. These results suggest that the SuML-DG pathway is capable of supporting the increase of theta and gamma power in the DG observed during PS and plays an important modulatory role of DG network activity during this state.\n\nSignificant statementAn increase of theta and gamma power in the dentate gyrus (DG) is an hallmark of paradoxical (REM) sleep (PS) and is suggested to promote learning and memory consolidation by synchronizing hippocampal networks and increasing its outputs to cortical targets. However the neuronal networks involved in such control of DG activity during PS are poorly understood. The present study identifies a population of GABA/Glutamate neurons in the lateral supramammllary nucleus (SuML) innervating the DG that could support such control during PS. Indeed, we show that activation of these SuML-DG projections increase theta power and frequency as well as gamma power in the DG specifically during PS and modulate activity of a subset of DG granule cells.

neuroscience↗