Biology subjects

Joseph, O.

Publications and source records attributed to Joseph, O..

2 recordsLinked to original sources

bioRxiv2025

Anatomical and molecular organization of the nociceptive medial thalamus

The medial thalamus (MTh) is a critical hub for integrating the affective and motivational dimensions of pain, yet its cellular and circuit organization remains poorly defined. Here, we combine activity-dependent genetic tagging, whole-brain clearing and light-sheet imaging, single-cell transcriptomics, and viral circuit tracing to build a comprehensive anatomical and molecular atlas of nociceptive and opioidergic neurons within the MTh. We show that acute and chronic pain activate distinct, spatially localized microdomains across multiple MTh subnuclei, including the central medial, interanteromedial, mediodorsal, and xiphoid nuclei. Activity-dependent tagging reveals a stable ensemble of nociceptive neurons that remains engaged across acute and chronic pain states, suggesting persistent thalamic encoding of affective nociception. Using fluorescent in situ hybridization, we find that most nociceptive-activated neurons express Oprm1, and that nearly all Oprm1+ neurons are activated by nociceptive stimuli, identifying a pain-active, {micro}-opioid receptor-expressing population in MTh (MThMOR). Rabies-based tracing demonstrates that MThMOR neurons receive convergent inputs from nociceptive and inhibitory regions including the anterior cingulate cortex, periaqueductal gray, parabrachial nucleus, and habenula, while projecting broadly to cortical, subcortical, and brainstem structures involved in pain, arousal, and motivation. Enkephalinergic inputs to MTh arise from distinct, non-nociceptive populations, suggesting parallel pathways for nociceptive transmission and endogenous opioid modulation. Together, these findings define the anatomical and molecular organization of the nociceptive medial thalamus and highlight MThMOR neurons as a cell-type-specific substrate for the development of targeted opioid-based pain therapies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=57 SRC="FIGDIR/small/692629v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@a1e6b3org.highwire.dtl.DTLVardef@13112eborg.highwire.dtl.DTLVardef@d125caorg.highwire.dtl.DTLVardef@107fd80_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

AxoDen: An Algorithm for the Automated Quantification of Axonal Density in defined Brain Regions

The rodent brain contains 70,000,000+ neurons interconnected via complex axonal circuits with varying architectures. Neural pathologies are often associated with anatomical changes in these axonal projections and synaptic connections. Notably, axonal density variations of local and long-range projections increase or decrease as a function of the strengthening or weakening, respectively, of the information flow between brain regions. Traditionally, histological quantification of axonal inputs relied on assessing the mean fluorescence intensity within a rectangle placed in the brain region-of-inter-est. Despite yielding valuable insights, this conventional method is notably susceptible to background fluorescence, post-acquisition adjustments, and inter-researcher variability. Additionally, it fails to account for the non-uniform innervation across brain regions, thus overlooking critical data such as innervation percentages and axonal distribution patterns. In response to these challenges, we introduce AxoDen, an open-source semi-automated platform designed to increase the speed and rigor of axon quantifications for basic neuroscience discovery. AxoDen processes user-defined brain regions-of-interests incorporating dynamic thresholding of grayscales-transformed images to facilitate binarized pixel measure-ments. Thereby AxoDen segregates the image content into signal and non-signal categories, effectively eliminating background interference and enabling the exclusive measurement of fluorescence from axonal projections. AxoDen provides detailed and accurate representations of axonal density and spatial distribution. AxoDens advanced yet user-friendly platform enhances the reliability and efficiency of axonal density analysis and facilitates access to unbiased high-quality data analysis with no technical background or coding experience required. AxoDen is freely available to everyone as a valuable neuroscience tool for dissecting axonal innervation patterns in precisely defined brain regions.

neuroscience↗