Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ...ventromedial medulla (RVM) has been the most studied, whereas little is known about direct corticospinal modulation. Here, we found that stimulation in the anterior cingulate cortex (ACC) potentiated spinal excitatory synaptic transmission and this modulation is independent of the RVM. Peripheral nerve injury enhanced the spinal synaptic transmission and occluded the ACC-spinal cord facilitation. Inhibition of ACC reduced the enhanced spinal synaptic transmission caused by nerve injury. Finally, using optogenetics, we showed that selective activation of ACC-spinal cord projecting neurons caused behavioral pain sensitization, while inhibiting the projection induced analgesic effects. Our results provide strong evidence that ACC stimulation facilitates spinal sensory excitatory transmission by a RVM-independent manner, and that such top-down facilitation may contribute to the process of chronic neuropathic pain.
The performance of Pd/Pt-based electrocatalysts is closely correlated with their surface structure, size and composition. Herein, we prepared uniformly distributed ultra-small PtPd alloyed ...nanoparticles (PtPd ANPs, ∼5 nm) within a robust three-dimensional nitrogen-doped reduced graphene oxide (3D-N-rGO) under hydrothermal conditions. l-Hydroxyproline was employed as reductant, N-doping and swelling agent for 3D-N-rGO. The size and shape of graphene hydrogels were easily adjusted by controlling the reaction temperature, and the formation mechanism was discussed in details. Then, the product was explored for ethylene glycol oxidation reaction (EGOR) and hydrogen evolution reaction (HER). The catalytic activity of PtPd ANPs/3D-N-rGO towards HER is close to the state-of-the-art Pt/C catalyst, and better than that of Pt/C in the case of EGOR. This study has shed some lights on the universal approach to develop next-generation catalysts, which is of great significance for direct alcohol fuel cells.
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•PtPd ANPs/3D-N-rGO was fabricated by a facile L-hyp-mediated hydrothermal method.•L-Hyp was employed as reductant, N-doping and swelling agent for 3D-N-rGO.•The graphene hydrogels were easily modulated by the hydrothermal temperature.•The nanocomposite had outstanding catalytic activity and durability towards EGOR and HER.
Abstract
Biohybrid neural interfaces (BHNIs) are a new class of neuromodulating devices that integrate neural microelectrode arrays (MEAs) and cell transplantation to improve treatment of nerve ...injuries and disorders. However, current BHNI devices are made from abiotic materials that are usually bio‐passive, non‐biodisintegratable, or rigid, which restricts encapsulated cell activity and host nerve reconstruction and frequently leads to local tissue inflammation. Herein, the first MEA composed of all disintegratable hydrogel tissue scaffold materials with synergistic performances of tissue conformal adhesiveness, MEA technologies, tissue scaffolding and stem cell therapy on a time scale appropriate for nerve tissue repair is proposed. In particular, the MEA conductive tracks are made from extracellular matrix (ECM)‐based double‐cross‐linked dual‐electrically conductive hydrogel (ECH) systems with robust tissue‐mimicking chemical/physical properties, electrical conductivity, and an affinity for neural progenitor stem cells. Meanwhile, the MEA hydrogel substrate prepared from transglutaminase‐incorporated gelatin/silk precursors simultaneously promotes gelation and interfacial adhesion between all MEA stacks, leading to rapid and scalable device integration. When the full hydrogel MEA is subjected to various mechanical stimuli and moisture, it is structurally stable with a low impedance (4 ± 3 kΩ) comparable to a recently reported benchmark. With seamless lamination around peripheral nerve fibers, the device permits successive neural signal monitoring for wound condition evaluation, while demonstrating synergistic effects of spatiotemporally controlled electrical stimulation and cell transplantation to accelerate restoration of motor function. This BHNI is completely degraded by 1 month thus eliminating the need for surgical retrieval to stably remain, interact, and further fuse with host tissues, successfully exhibiting compatible integration of biology and an implanted electrical system.
We carry out a combined theoretical and experimental investigation on the population distributions in the ground and excited states of tunnel-ionized nitrogen molecules at various driver wavelengths ...in the near- and midinfrared range. Our results reveal that efficient couplings (i.e., population exchanges) between the ground N_{2}^{+}(X^{2}Σ_{g}^{+}) state and the excited N_{2}^{+}(A^{2}Π_{u}) and N_{2}^{+}(B^{2}Σ_{u}^{+}) states occur in strong laser fields. The couplings result in a population inversion between the N_{2}^{+}(X^{2}Σ_{g}^{+}) and N_{2}^{+}(B^{2}Σ_{u}^{+}) states at wavelengths near 800 nm, which is verified by our experimental observation of the amplification of a seed at ∼391 nm. The result provides insight into the mechanism of free-space nitrogen ion lasers generated in remote air with strong femtosecond laser pulses.
We propose and demonstrate a terahertz (THz) oscilloscope for recording time information of an ultrashort electron beam. By injecting a laser-driven THz pulse with circular polarization into a ...dielectric tube, the electron beam is swept helically such that the time information is uniformly encoded into the angular distribution that allows one to characterize both the temporal profile and timing jitter of an electron beam. The dynamic range of the measurement in such a configuration is significantly increased compared to deflection with a linearly polarized THz pulse. With this THz oscilloscope, nearly 50-fold longitudinal compression of a relativistic electron beam to about 15 fs (rms) is directly visualized with its arrival time determined with 3 fs accuracy. This technique bridges the gap between streaking of photoelectrons with optical lasers and deflection of relativistic electron beams with radio-frequency deflectors, and should have wide applications in many ultrashort electron-beam-based facilities.
Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the ...molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.
The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types ...remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.
As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a ...variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVT
-CeA-vlPAG
circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.
Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVT
-CeA-vlPAG
pathway in a descending facilitatory mechanism underlying neuropathic pain.
Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural ...mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.
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•A new mouse model is established to study long-term observational pain•ICR-BLAR pathway is required for the formation/consolidation of observational pain•Glutamate encodes the synaptic transmission from the ICR to BLAR•Synaptotagmin-2 and RIM3 are key signals for the regulation of observational pain
Zhang et al. show that sibling but not stranger observer mice exhibit observational pain, which requires glutamate transmission from the insular cortex to the basolateral amygdala and is regulated by synaptotagmin-2 and RIM3.
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