Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates ...inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs. VNS broadly stimulates these fibers without specificity. We used optogenetics to selectively stimulate vagus efferent or afferent fibers. Anterograde efferent fiber stimulation or anterograde (centripetal) sensory afferent fiber stimulation both conferred kidney protection from ischemia-reperfusion injury. We identified the C1 neurons-sympathetic nervous system-splenic nerve-spleen-kidney axis as the downstream pathway of vagus afferent fiber stimulation. Our study provides a map of the neural circuits important for kidney protection induced by VNS, which is critical for the safe and effective clinical application of VNS for protection from acute kidney injury.
The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay ...neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus.
Abstract
Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to ...current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.
Activation of rostral ventrolateral medullary catecholaminergic (RVLM-CA) neurons e.g., by hypoxia is thought to increase sympathetic outflow thereby raising blood pressure (BP). Here we test whether ...these neurons also regulate breathing and cardiovascular variables other than BP. Selective expression of ChR2-mCherry by RVLM-CA neurons was achieved by injecting Cre-dependent vector AAV2-EF1α-DIO-ChR2-mCherry unilaterally into the brainstem of dopamine-β-hydroxylase(Cre/0) mice. Photostimulation of RVLM-CA neurons increased breathing in anesthetized and conscious mice. In conscious mice, photostimulation primarily increased breathing frequency and this effect was fully occluded by hypoxia (10% O(2)). In contrast, the effects of photostimulation were largely unaffected by hypercapnia (3 and 6% CO(2)). The associated cardiovascular effects were complex (slight bradycardia and hypotension) and, using selective autonomic blockers, could be explained by coactivation of the sympathetic and cardiovagal outflows. ChR2-positive RVLM-CA neurons expressed VGLUT2 and their projections were mapped. Their complex cardiorespiratory effects are presumably mediated by their extensive projections to supraspinal sites such as the ventrolateral medulla, the dorsal vagal complex, the dorsolateral pons, and selected hypothalamic nuclei (dorsomedial, lateral, and paraventricular nuclei). In sum, selective optogenetic activation of RVLM-CA neurons in conscious mice revealed two important novel functions of these neurons, namely breathing stimulation and cardiovagal outflow control, effects that are attenuated or absent under anesthesia and are presumably mediated by the numerous supraspinal projections of these neurons. The results also suggest that RVLM-CA neurons may underlie some of the acute respiratory response elicited by carotid body stimulation but contribute little to the central respiratory chemoreflex.
Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result of autonomic responses ...triggered by prostaglandin E2 action on EP3 receptors expressed by neurons in the median preoptic nucleus (MnPO
neurons). To investigate the identity of MnPO
neurons, we first used
hybridization to show coexpression of EP3R and the VGluT2 transporter in MnPO neurons. Retrograde tracing showed extensive direct projections from MnPO
but few from MnPO
neurons to a key site for fever production, the raphe pallidus. Ablation of MnPO
but not MnPO
neurons abolished fever responses but not changes in Tb induced by behavioral stress or thermal challenges. Finally, we crossed EP3R conditional knock-out mice with either VGluT2-IRES-cre or Vgat-IRES-cre mice and used both male and female mice to confirm that the neurons that express EP3R and mediate fever are glutamatergic, not GABAergic. This finding will require rethinking current concepts concerning the central thermoregulatory pathways based on the MnPO
neurons being GABAergic.
Body temperature is regulated by the CNS. The rise of the body temperature, or fever, is an important brain-orchestrated mechanism for fighting against infectious or inflammatory disease, and is tightly regulated by the neurons located in the median preoptic nucleus (MnPO). Here we demonstrate that excitatory MnPO neurons mediate fever and examine a potential central circuit underlying the development of fever responses.
► A simple calcium phosphate conversion-coating route was exploited on magnesium alloy AZ91D. ► Concentration of Ca2+ and PO43- ions in the solution determined the coating composition. ► Low PO43- ...coating bath produced a coating containing high hydroxyapatite content. ► While high PO43- solution was beneficial for high proportion of DCPD deposition. ► Results revealed that the hydroxyapatite coating offered better corrosion resistance than DCPD.
The effect of varying Ca2+total and PO43-total concentrations (nine conditions in total) on the formation of calcium phosphate conversion coatings on magnesium alloy AZ91D was investigated. Corrosion performance was evaluated by measurement of polarisation behaviour and also by salt spray testing. A consistent trend was observed of improved corrosion performance with reduced ionic concentrations. Low PO43-total concentration was found to be especially important for the attainment of good corrosion resistance. Both direct measurement using X-ray photoelectron spectroscopy and chemical modelling using MEDUSA software indicated an increase in hydroxyapatite content of the coating accompanying the improved corrosion resistance.
The two-stage vibration isolation and positioning platform provides passive and active isolation in all directions and translation. It uses a unique combination of position sensors, geophones and ...broadband seismometers to provide unprecedented levels of isolation.
•The paper presents the two-stage vibration isolation and positioning platform used in Advanced LIGO gravitational waves detectors.•The system can support a 1000kg of sensitive equipment and operate in ultra-high vacuum.•Each of the two stages provide passive and active isolation in all directions of translation and rotation (12 axis).•The active control strategy uses a unique combination of relative sensors, geophones and broadband seismometers.•The system reduces the motion to the level of 10−11 m/Hz at 1Hz and 10−12 m/Hz at 10Hz.
New generations of gravity wave detectors require unprecedented levels of vibration isolation. This paper presents the final design of the vibration isolation and positioning platform used in Advanced LIGO to support the interferometer's core optics. This five-ton two-and-half-m wide system operating in ultra-high vacuum. It features two stages of isolation mounted in series. The stages are imbricated to reduce the overall height. Each stage provides isolation in all directions of translation and rotation. The system is instrumented with a unique combination of low noise relative and inertial sensors. The active control provides isolation from 0.1Hz to 30Hz. It brings the platform motion down to 10−11 m/Hz at 1Hz. Active and passive isolation combine to bring the platform motion below 10−12 m/Hz at 10Hz. The passive isolation lowers the motion below 10−13 m/Hz at 100Hz. The paper describes how the platform has been engineered not only to meet the isolation requirements, but also to permit the construction, testing, and commissioning process of the fifteen units needed for Advanced LIGO observatories.
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