DNA from macrophages induces fibrosis and vasculopathy through POLR3A/STING/type I interferon axis in systemic sclerosis.

OBJECTIVE: To clarify the role of RNA polymerase III A (POLR3A)/type I IFN in the pathogenesis of SSc. METHODS: Cytosolic DNA and stimulator of IFN genes (STING) pathway in skin or serum of SSc patients were detected by immunofluorescence, immunohistochemistry and western blotting. DNA from human macrophages was transfected to SSc fibroblasts or human umbilical vein endothelial cells (HUVECs) and then markers of POLR3A/STING pathway were detected by real-time qPCR, western blotting and confocal microscopy. After H151 treatment or knocking down POLR3A/STING, type I IFN response, monocytes adhesion and activation of fibroblasts and HUVECs were evaluated. Regulation of IFN regulatory factor 3 (IRF3) on monocyte chemoattractant protein-1 (MCP-1) was determined by chromatin immunoprecipitation. In bleomycin (BLM)-induced SSc mice, the effect of STING knockout or H151 on vasculopathy and fibrosis was assessed. RESULTS: Cytosolic DNA, colocalization of STING with alpha-smooth muscle actin (α-SMA) or CD31 in the skin, and STING pathway in the serum of SSc patients were increased. Macrophage-derived DNA stimulated the translocation of POLR3A from nucleus to the perinuclear region near STING and activated POLR3A/STING/type I IFN response, monocytes adhesion and MCP-1 expression in fibroblasts/HUVECs and collagen overproduction of fibroblasts. The activated IRF3 bound to the promoter of MCP-1. STING deficiency or H151 administration ameliorated fibrosis and vasculopathy both in vitro and in BLM-induced SSc mice. CONCLUSIONS: SSc presented increased DNA leakage and STING pathway activation. DNA from macrophages induced type I IFN signature of fibroblasts and ECs through POLR3A/STING pathway. Blocking POLR3A/STING axis provides a new therapeutic target for SSc.

Cathepsin B/NLRP3/GSDMD axis-mediated macrophage pyroptosis induces inflammation and fibrosis in systemic sclerosis.

BACKGROUND: Pyroptosis is a newly discovered type of programmed cell death associated with inflammatory and fibrotic diseases. Macrophages play an important role in inducing early immune inflammation in systemic sclerosis (SSc). OBJECTIVE: To investigate the effect of macrophages pyroptosis on fibrosis of SSc. METHODS: Pyroptosis/inflammatory markers in serum and skin of SSc patients were detected. Bleomycin (BLM) was subcutaneously injected to establish SSc mouse model. The levels of pyroptosis markers, dermal thickness and collagen deposition in skin were assessed before and after the administration of pyroptosis inhibitors, including MCC950, Disulfiram and necrosulfonamide (NSA). Human-derived monocyte-macrophage cell line (THP-1) or mouse bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and stimulated by silicon dioxide (SiO2) to induce cell pyroptosis. Fibroblasts from patients with SSc were co-cultured with pyroptotic THP-1 cells, and the collagen production was assessed. RESULTS: Pyroptotic/inflammatory proteins, including NLRP3, cleaved-Caspase (CASP)1, GSDMD-N terminal and IL-18 were increased in the serum, and ASC aggregation and GSDMD were elevated in macrophages in the skin of SSc patients. SSc mice showed increased pyroptosis markers, dermal thickness and collagen deposition in skins, which were alleviated by MCC950, Disulfiram and NSA. Pyroptosis of THP-1 cells and BMDMs was induced by LPS/SiO2, and it was reduced by the inhibitors of Cathepsin B, NLRP3, CASP1 and GSDMD. Co-culture with pyroptotic THP-1 cells increased the fibrotic proteins in fibroblasts, which were alleviated by pyroptosis inhibitors. CONCLUSIONS: SSc patients and BLM-induced mouse model presented increased pyroptosis. LPS/SiO2-induced macrophage pyroptosis promoted fibrosis of SSc through Cathepsin B/NLRP3/GSDMD pathway.

Somatosensory cortical signature of facial nociception and vibrotactile touch-induced analgesia.

Pain relief by vibrotactile touch is a common human experience. Previous neurophysiological investigations of its underlying mechanism in animals focused on spinal circuits, while human studies suggested the involvement of supraspinal pathways. Here, we examine the role of primary somatosensory cortex (S1) in touch-induced mechanical and heat analgesia. We found that, in mice, vibrotactile reafferent signals from self-generated whisking significantly reduce facial nociception, which is abolished by specifically blocking touch transmission from thalamus to the barrel cortex (S1B). Using a signal separation algorithm that can decompose calcium signals into sensory-evoked, whisking, or face-wiping responses, we found that the presence of whisking altered nociceptive signal processing in S1B neurons. Analysis of S1B population dynamics revealed that whisking pushes the transition of the neural state induced by noxious stimuli toward the outcome of non-nocifensive actions. Thus, S1B integrates facial tactile and noxious signals to enable touch-mediated analgesia.

Inhibition of JAK1/STAT3 pathway by 2-methoxyestradiol ameliorates psoriatic features in vitro and in an imiquimod-induced psoriasis-like mouse model.

Psoriasis is characterized by hyperproliferative keratinocytes, dilated capillaries and leukocyte infiltration. 2-Methoxyestradiol (2-ME) has shown significant inhibition on proliferation, angiogenesis and inflammation. To evaluate the anti-psoriatic potential of 2-ME, psoriasis-like dermatitis was induced by topical application of imiquimod (IMQ) on the dorsal skin of C57BL/6 mice for seven consecutive days, followed by treatment of vehicle or 2-ME ointment from Day 4 on. The psoriasis area and severity index (PASI) was assessed daily. On Day 8, skin histology and spleen index were assessed. The effects of 2-ME on the proliferation, apoptosis, cell cycle, vascular endothelial growth factor A (VEGFA), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways of HaCaT cells stimulated by interleukin-17 (IL-17A) were detected, together with its effect on the proliferation, tube formation and VEGF receptor expression of human umbilical vein endothelial cells (HUVECs). We found that topical 2-ME treatment significantly improved IMQ-induced psoriasis-like dermatitis and decreased the PASI scores, the activation of STAT3 in the skin (P < 0.05), and the spleen index in mice (P < 0.01). In vitro, 2-ME inhibited the proliferation of HaCaT cells by inducing apoptosis and G2/M phase arrest (P < 0.01). Moreover, 2-ME suppressed IL-17A-induced VEGFA (2.5 µM: P < 0.05; 5 µM: P < 0.01) and phosphorylation of STAT3 by blocking p-JAK1 in HaCaT cells and prevented tube formation (P < 0.01) and proliferation by targeting VEGF receptors 1 (VEGFR1) and 2 (VEGFR2) in HUVECs. We conclude that 2-ME alleviated psoriasis in vivo and in vitro by inhibiting JAK1/STAT3 pathway and was a promising therapeutic agent for psoriasis.

The whisking oscillator circuit.

Central oscillators are primordial neural circuits that generate and control rhythmic movements1,2. Mechanistic understanding of these circuits requires genetic identification of the oscillator neurons and their synaptic connections to enable targeted electrophysiological recording and causal manipulation during behaviours. However, such targeting remains a challenge with mammalian systems. Here we delimit the oscillator circuit that drives rhythmic whisking-a motor action that is central to foraging and active sensing in rodents3,4. We found that the whisking oscillator consists of parvalbumin-expressing inhibitory neurons located in the vibrissa intermediate reticular nucleus (vIRtPV) in the brainstem. vIRtPV neurons receive descending excitatory inputs and form recurrent inhibitory connections among themselves. Silencing vIRtPV neurons eliminated rhythmic whisking and resulted in sustained vibrissae protraction. In vivo recording of opto-tagged vIRtPV neurons in awake mice showed that these cells spike tonically when animals are at rest, and transition to rhythmic bursting at the onset of whisking, suggesting that rhythm generation is probably the result of network dynamics, as opposed to intrinsic cellular properties. Notably, ablating inhibitory synaptic inputs to vIRtPV neurons quenched their rhythmic bursting, impaired the tonic-to-bursting transition and abolished regular whisking. Thus, the whisking oscillator is an all-inhibitory network and recurrent synaptic inhibition has a key role in its rhythmogenesis.

Gut microbiota characterization in Chinese patients with alopecia areata.

BACKGROUND: The gut microbiota is known to play a key role in autoimmune diseases. OBJECTIVES: To identify and compare the characteristics in the gut microbial composition of patients with alopecia areata (AA) and healthy controls (HCs). METHODS: In a cross-sectional discovery cohort, we enrolled 33 patients with AA and 35 HCs from the same geographic location in Shanghai, China. The 16S rRNA gene sequencing and bioinformatic analyses were conducted to analyze DNA extracted from the subjects. RESULTS: The α-diversity of the AA group demonstrated no statistically significant differences compared with the HC group (P > 0.05). However, the overall gut microbial communities in the AA group were distinct from the HCs (P = 0.0096). We also adopted a random forest model to select three AA-associated OTU biomarkers: OTU1237(Achromobacter), OTU257(Megasphaera), and OTU1784(Lachnospiraceae Incertae Sedis). CONCLUSION: The overall gut microbial composition for AA was distinct from that of HCs. The gut microbial markers we identified may potentially be used for earlier diagnosis and as therapeutic targets.

Constructing an adult orofacial premotor atlas in Allen mouse CCF.

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors.

Palmar erythema and palmar papules as predictors for dermatomyositis-related acute/subacute interstitial lung disease: a retrospective study.

OBJECTIVES: DM-related acute/subacute interstitial lung disease (A/S-ILD) remains a big therapeutic challenge due to its insidious onset and rapid development. In the present study, we aimed to investigate the association between clinical features of DM and ILD. METHODS: We retrospectively assessed skin manifestations, muscle damage, laboratory tests, concurrent ILD and malignancy in 207 patients with DM and analysed the high-risk factors for ILD. RESULTS: In the 207 DM patients, 153 patients had ILD, in which 131 had chronic ILD (CILD) and 22 had A/S-ILD. The proportions of mechanic's hands, palmar papules and muscle weakness, as well as anti-melanoma differentiation-associated gene 5 (MDA5) antibody and lactic dehydrogenase (LDH), alanine aminotransferase (ALT) and ferritin in the ILD group were significantly higher compared with the non-ILD group. The onset age over 56 years, mechanic's hands and muscle weakness were independent predictive factors for ILD. The proportions of palmar papules, palmar erythema, anti-MDA5 antibody, ALT, aspartate aminotransferase (AST), LDH and ESR in the A/S-ILD group were higher compared with the CILD group. Palmar erythema and palmar papules were independent predictive factors for A/S-ILD. Palmar papules were positively correlated with anti-MDA5 antibody. CONCLUSION: The onset age over 56 years, mechanic's hands or muscle weakness predicted the incidence of DM-related ILD, while palmar erythema or palmar papules could predict potential DM-related A/S-ILD.

The PD-1/PD-L1 pathway in murine hair cycle transition: a potential anagen phase regulator.

Programmed cell death protein-1 (PD-1) is primarily recognized as an inhibitory receptor involved in the regulation of immunological tolerance. However, recent studies have indicated that PD-1/PD-L1 signaling could also regulate the functions of nonimmune cells and may be involved in regulating hair biology. In this study, we showed in a mouse model of depilation-induced hair cycling that PD-1/PD-L1 are expressed in the murine epidermis and hair follicle (HF) in a hair cycle-dependent manner. During HF morphogenesis, PD-1 expression was strongly decreased during the anagen phase compared with the catagen and telogen phases. PD-L1 expression was enhanced during the catagen phase compared with the anagen and telogen phases. Moreover, direct blockade of PD-L1 not only accelerated hair anagen phase onset but also delayed catagen progression. In conclusion, our findings indicated that PD-1/PD-L1 signaling may act as a negative regulator of hair cycle transition. Anti-PD-1/PD-L1 therapy may thus be a promising strategy for treating anagen-reduced hair loss.

General anesthetics activate a potent central pain-suppression circuit in the amygdala.

General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeAGA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeAGA neurons. CeAGA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeAGA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeAGA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeAGA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeAGA as a potential powerful therapeutic target for alleviating chronic pain.

Remarkable improved photoelectric performance of SnS2 field-effect transistor with Au plasmonic nanostructures.

The development of photoelectric devices for high integration and miniaturization in the semiconductor industry can be pushed forward by the thriving research of two-dimensional layered metal dichalcogenides (2D-LMDs). SnS2 nanosheets have an evident photoresponse to both ultraviolet and partial visible light, but only with a fair photoelectric performance limited by their atomic-layer thickness. Here, we report a convenient and simple method to dramatically enhance the electrical and photoelectric performance of the SnS2 flake. By integrating SnS2 with Au plasmonic nanostructures, the photocurrent (I ph) increased by over 20 times. The corresponding responsivity (R), light gain (G), and detectivity (D*) have been improved by ∼2200%, 2200% and 600%, respectively. The responsivity and detectivity of the Au NPs-SnS2 field-effect transistor (FET) at 532 nm are 1125.9 A W-1 and 2.12 × 1011 Jones. Though atomically thin, the hybrid SnS2 photodetector, benefiting from local surface plasmonic resonance, achieves an excellent photoelectric performance that is not usually possible with a pristine SnS2-only device.

The mechanism of Co oxyhydroxide nano-islands deposited on a Pt surface to promote the oxygen reduction reaction at the cathode of fuel cells.

With the rapid development of fuel cell technology, the low reduction rate of oxygen on Pt-based cathodes is generally considered the main obstacle. Pt/transition metal alloys (Pt-Ms) or Pt/transition metal oxides (Pt-MO x ) can be formed by doping transition metal atoms into the lattice of the Pt layer or depositing onto the surface of the Pt layer to intensify the catalytic activity of the electrodes. In this work, a stepwise solution chemical reduction method for high dispersion of cobalt oxyhydroxide (-OCoOH) deposited onto the facet of Pt as nano-islands and the mechanism of promoting the oxygen reduction reaction (ORR) at the cathode have been investigated by density functional theory (DFT) calculation. As a result, the electrocatalytic activity of Pt with nano-island -OCoOH structure was 3.6 times that of the Pt/C catalyst, which indicated that promoting the desorption of the first O atom and weakening the adsorption capacity of the interfacial junction Pt for the second O atom from adsorbed oxygen attributed to the migration of d-band center in Pt and the existence of the Co hydroxyl group.

Mechanism analysis of Au, Ru noble metal clusters modified on TiO2 (101) to intensify overall photocatalytic water splitting.

Accelerating the separation and migration of photo-carriers (electron-hole pairs) to improve the photo-quantum utilization efficiency in photocatalytic overall water splitting is highly desirable. Herein, the photo-deposition of Ru or Au noble metal clusters with superior electronic properties as a co-catalyst on the (101) facet of anatase TiO2 and the mechanism of intensifying the photocatalysis have been investigated by calculation based density functional theory (DFT). As a result, the as-synthesized Ru/TiO2 and Au/TiO2 exhibit high hydrogen evolution reaction (HER) activity. Such a greatly enhanced HER is attributed to the interfacial interactivity of the catalysts due to the existence of robust chemical bonds (Ru-O-Ti, Au-O-Ti) as electron-traps that provide the photogenerated electrons. In addition, the formation of new degenerate energy levels due to the existence of Ru-4d and Au-5d electronic impurity states leads to the narrowing of the band gap of the catalysts. In addition, the as-synthesized Au/TiO2 exhibits more faster HER rate than Ru/TiO2, which is attributed to the effects of surface plasmon resonance (SPR) as a synergistic effect of plasmon-induced 'hot' electrons that enhance the harvesting of the final built-in electric field and promote the migration and separation of the photo-carriers, which efficiently facilitates hydrogen evolution from the photocatalytic overall water splitting reaction.

Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia.

OBJECTIVES: To investigate whether autophagy mediates 2-methoxyestradiol (2-ME)-inhibited hypoxia-induced fibrosis and endothelial-to-mesenchymal transition (endoMT) in SSc. METHODS: Autophagy in the skin of SSc patients was assessed by transmission electron microscopy. SSc skin fibroblasts and human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic (1% O2) conditions with 2-ME or autophagy inhibitor. Collagen I and connective tissue growth factor (CTGF) in fibroblasts and vascular endothelial (VE)-cadherin, CD31, vimentin and α-smooth muscle actin (α-SMA) in HUVECs were examined by western blotting. Autophagic markers were evaluated by confocal microscopy and immunofluorescence. RESULTS: SSc skins presented increased autolysosomes, LC3-II, collagen I and CTGF. Hypoxia-challenged fibroblasts and HUVECs formed more autophagosomes and autolysosomes, with increased LC3 and decreased P62. Meanwhile, hypoxia increased collagen I and CTGF in fibroblasts and increased vimentin and α-SMA but decreased VE-cadherin and CD31 in HUVECs. Bafilomycin A1 increased LC3-II and P62 in fibroblasts and HUVECs and decreased collagen I and CTGF in fibroblasts and vimentin and α-SMA in HUVECs, while upregulating VE-cadherin and CD31. 3-methyladenine decreased autophagy and fibrosis in fibroblasts and endothelial-to-mesenchymal transition in HUVECs. 2-ME-treated HUVECs showed more autophagosomes and fewer autolysosomes while 2-ME-treated fibroblasts showed fewer of both. Moreover, 2-ME decreased LC3-II and increased P62 in fibroblasts and increased both in HUVECs. Inhibition of autophagy by 2-ME showed the same effect with bafilomycin A1 on fibroblast collagen synthesis as well as endothelial and mesenchymal markers in HUVECs. CONCLUSION: Autophagy mediated hypoxia-induced fibroblast collagen synthesis and endoMT in SSc, which could be reversed by 2-ME.

Effect of Ru, Rh, Mo, and Pd Adsorption on the Electronic and Optical Properties of Anatase TiO2(101): A DFT Investigation.

Adsorbed metal atoms and metal doping onto TiO2 can effectively enhance the optical and photocatalytic activity of photocatalytic efficiency of titanium dioxide (TiO2), favoring the extension of its optical absorption spectrum and the efficiency of hydrogen generation. To investigate the possible mechanism causing potential improvement of photocatalytic activity, the electronic and optical properties of the anatase TiO2(101) plane with different adsorbed metal atom have been theoretically calculated through density functional theory (DFT) method. Adsorption of Pd and Ru atoms increases the delocalization of the density of states, with an impurity state near the Fermi level. Moreover, the investigated adsorbed metal atoms (Mo, Pd, Ru, Rh) narrow the band gap of anatase TiO2, thus enhancing the probability of photoactivation by visible light. The orbital hybridization of the d orbit from the adsorbed metal atom and the p orbit from the O of the defect site increases the Schottky barrier of the electronic structure.

SnSe2 Field-Effect Transistor with High On/Off Ratio and Polarity-Switchable Photoconductivity.

SnSe2 field-effect transistor was fabricated based on exfoliated few-layered SnSe2 flake, and its electrical and photoelectric properties have been investigated in detail. With the help of a drop of de-ionized (DI) water, the SnSe2 FET can achieve an on/off ratio as high as ~ 104 within 1 V bias, which is ever extremely difficult for SnSe2 due to its ultrahigh carrier density (1018/cm3). Moreover, the subthreshold swing and mobility are both improved to ∼ 62 mV/decade and ~ 127 cm2 V-1 s-1 at 300 K, which results from the efficient screening by the liquid dielectric gate. Interestingly, the SnSe2 FET exhibits a gate bias-dependent photoconductivity, in which a competition between the carrier concentration and the mobility under illumination plays a key role in determining the polarity of photoconductivity.

2-Methoxyestradiol inhibits hypoxia-induced scleroderma fibroblast collagen synthesis by phosphatidylinositol 3-kinase/Akt/mTOR signalling.

Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc. Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 µM). The protein levels of HIF-1α, CTGF, collagen I, p-Akt and p-mTOR were examined by western blotting or immunofluorescence. Apoptosis and cell cycle of fibroblasts were assessed by flow cytometry and by measuring caspase 3 activity, and cell proliferation was evaluated by Cell Counting Kit-8. Results: The expressions of HIF-1α and CTGF were increased in skins of SSc patients compared with healthy controls. Hypoxia up-regulated the protein levels of HIF-1α, CTGF and collagen I in SSc fibroblasts. In contrast, 2-ME inhibited PI3K/Akt/mTOR pathway and down-regulated protein levels of HIF-1α, CTGF and collagen I. Knockdown of HIF-1α reduced expressions of CTGF and collagen I, which were further down-regulated by 2-ME intervention. Moreover, 2-ME promoted the apoptosis and inhibited the proliferation of SSc fibroblasts by arresting the cell cycle at the G2/M phase. Conclusion: 2-ME reduced the production of CTGF and collagen I in SSc fibroblasts induced by hypoxia through PI3K/Akt/mTOR/HIF-1α signalling and inhibited the proliferation of fibroblasts. These findings suggested that 2-ME could be employed as a promising antifibrotic therapy for SSc.

MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline.

In vivo calcium imaging using a 1-photon-based miniscope and a microendoscopic lens enables studies of neural activities in freely behaving animals. However, the high and fluctuating background, the inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals emitted from imaged neurons inherent in this 1-photon imaging method present major challenges for extracting neuronal signals reliably and automatically from the raw imaging data. Here, we develop a unifying algorithm called the miniscope 1-photon imaging pipeline (MIN1PIPE), which contains several stand-alone modules and can handle a wide range of imaging conditions and qualities with minimal parameter tuning and automatically and accurately isolate spatially localized neural signals. We have quantitatively compared MIN1PIPE with other existing partial methods using both synthetic and real datasets obtained from different animal models and show that MIN1PIPE has superior efficiency and precision in analyzing noisy miniscope calcium imaging data.

Parallel Inhibitory and Excitatory Trigemino-Facial Feedback Circuitry for Reflexive Vibrissa Movement.

Animals employ active touch to optimize the acuity of their tactile sensors. Prior experimental results and models lead to the hypothesis that sensory inputs are used in a recurrent manner to tune the position of the sensors. A combination of electrophysiology, intersectional genetic viral labeling and manipulation, and classical tracing allowed us to identify second-order sensorimotor loops that control vibrissa movements by rodents. Facial motoneurons that drive intrinsic muscles to protract the vibrissae receive a short latency inhibitory input, followed by synaptic excitation, from neurons located in the oralis division of the trigeminal sensory complex. In contrast, motoneurons that retract the mystacial pad and indirectly retract the vibrissae receive only excitatory input from interpolaris cells that further project to the thalamus. Silencing this feedback alters retraction. The observed pull-push circuit at the lowest-level sensorimotor loop provides a mechanism for the rapid modulation of vibrissa touch during exploration of peri-personal space.