Biology subjects

Xu, X. H.

Publications and source records attributed to Xu, X. H..

5 recordsLinked to original sources

bioRxiv2026

An expanded toolbox for genetic access to molecularly defined cortical intratelencephalic neuron subtypes

Among the multiple cortical glutamatergic neuron classes, intratelencephalic (IT) neurons represent the largest class and project within the cortex and striatum. IT neurons have been amplified and diversified throughout mammalian evolution and are thought to underlie increasingly complex mammalian cognition. However, despite their diversity and significance in cortical processes, few existing tools connect the molecular signatures to the projection patterns of distinct IT subtypes, limiting our ability to understand their organization and function at a subtype resolution. Here, we illustrate six novel gene knock-in mouse lines based on IT-specific markers, labeling subpopulations with unique cortico-cortical and corticostriatal projection patterns. These include two broad subpopulations with upper-layer (Cux1-Flp) versus lower-layer (Kcnh5-CreER) expression biases, two narrow upper-layer subpopulations with contrasting callosal (Wfs1-Flp) and local (Igfn1-Flp) projection patterns, and two narrow lower-layer subpopulations with contrasting bilateral (Deptor-CreER) versus ipsilateral-predominant (Ptprm-CreER) corticostriatal projection patterns. Upper-layer Wfs1+ and lower-layer Ptprm+ IT neurons also project to perirhinal/ectorhinal cortex with densities that vary across cortical areas. Finally, we use in vivo calcium imaging in mice performing a reach-withdraw-drink task to demonstrate subtype-specific temporal dynamics in upper-layer Wfs1+ versus lower-layer Deptor+ neurons. Our work expands the toolbox of transgenic mice to access molecularly defined IT neuron subpopulations.

neuroscience↗

bioRxiv2025

Motor Cortical Output Integrates Distorted Proprioceptive Feedback

Proprioceptive feedback from muscles is essential for continuous monitoring and precise control of limb movement, yet how such peripheral feedback is integrated into ongoing descending motor cortical dynamics remains largely unclear. Here we used precisely timed optogenetic stimulation of forelimb muscles to manipulate proprioceptive signals during a mouse reach-to-consume task. Mice were able to successfully reach and consume despite muscle stimulation-evoked forelimb deviations. Across the cortex, the caudal forelimb area (CFA) was preferentially activated by muscle-specific proprioceptive inputs and contributed to stabilizing perturbed forelimb movement. CFA extratelencephalic (ET) neurons encoded movement kinematics as well as proprioceptive feedback. At neuron population level, proprioceptive perturbations rapidly deflected CFA ET neural trajectories away from the task-relevant manifold yet exerted only limited effects on evolving task dynamics. These results reveal that descending cortical circuit implements activity subspace separation to encode and integrate distorted proprioceptive feedback while preserving task-relevant output.

neuroscience↗

bioRxiv2023

Cortical network and projection neuron types that articulate serial order in a skilled motor behavior

The coordination of forelimb and orofacial movements to compose an ethological reach-to-consume behavior likely involves neural communication across brain regions. Leveraging wide-field imaging and photo-inhibition to survey across the cortex, we identified a cortical network and a high-order motor area (MOs-c), which coordinate action progression in a mouse reach-and-withdraw-to-drink (RWD) behavior. Electrophysiology and photo-inhibition across multiple projection neuron types within the MOs-c revealed differential contributions of pyramidal tract and corticothalamic (CTMOs) output channels to action progression and hand-mouth coordination. Notably, CTMOs display sustained firing throughout RWD sequence and selectively enhance RWD-relevant activity in postsynaptic thalamus neurons, which also contribute to action coordination. CTMOs receive converging monosynaptic inputs from forelimb and orofacial sensorimotor areas and are reciprocally connected to thalamic neurons, which project back to the cortical network. Therefore, motor cortex corticothalamic channel may selectively amplify the thalamic integration of cortical and subcortical sensorimotor streams to coordinate a skilled motor sequence.

neuroscience↗

bioRxiv2022

A cortical circuit for orchestrating oromanual food manipulation

The seamless coordination of hands and mouth--whether in humans eating corn on the cob or mice extracting sunflower seeds--represents one of evolutions most sophisticated motor achievements. Whereas spinal and brainstem circuits implement basic forelimb and orofacial actions, whether there is a specialized cortical circuit that assembles these actions to enable skilled oromanual manipulation remains unclear. Here, we discover a cortical area and its cell-type-specific circuitry that govern oromanual food manipulation in mice. An optogenetic screen of cortical areas and projection neuron types identified a rostral forelimb-orofacial area (RFO), wherein activation of pyramidal tract (PTFezf2) and intratelencephalic (ITPlxnD1) neurons induced concerted posture, forelimb and orofacial movements resembling eating. In a freely moving pasta-eating behavior, pharmacological RFO inactivation impaired the sitting posture, hand recruitment, and oromanual coordination in pasta eating. RFO PTFezf2 and ITPlxnD1 activity was closely correlated with oromanual pasta manipulation and hand-assisted biting. Optogenetic inhibition revealed that PTsFezf2 regulate dexterous hand and mouth movements while ITsPlxnD1 play a more prominent role in oromanual coordination. RFO forms the hub of an extensive network, with reciprocal connections to cortical forelimb and orofacial sensorimotor areas, as well as insular and visceral areas. Within this cortical network, RFO PTsFezf2 project unilaterally to multiple subcortical, brainstem and spinal areas associated with forelimb and orofacial control, while ITsPlxnD1 project bilaterally to the entire network and the ventrolateral striatum, and can mediate concurrent forelimb and mouth movement in part through their striatal projection. Together, these findings uncover the cell-type-specific implementation of a cortical circuit that orchestrates oromanual manipulation, essential for skilled feeding.

neuroscience↗

bioRxiv2019

Natural naphthoquinones isolated from Lithospermum erythrorhizon suppress dextran sulfate sodium-induced murine experimental colitis

The purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1{beta} and TNF-), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-{kappa}B signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-{kappa}B to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).

biochemistry↗