The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral...Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.展开更多
Adult male mice emit highly complex ultrasonic vocalizations(USVs)in response to female conspecifics.Such US Vs,thought to facilitate courtship behaviors,are routinely measured as a behavioral index in mouse models of...Adult male mice emit highly complex ultrasonic vocalizations(USVs)in response to female conspecifics.Such US Vs,thought to facilitate courtship behaviors,are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism.While the regulation of US Vs by genetic factors has been extensively characterized,the neural mechanisms that control USV production remain largely unknown.Here,we report that optogenetic activation of the medial preoptic area(mPOA)elicited the production of USVs that were acoustically similar to courtship US Vs in adult mice.Moreover,mPOA vesicular GABA transporter-positive(Vgat +)neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons.Furthermore,ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males.Together,these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.展开更多
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金funded by the National Natural Science Foundation of China(32173021)the Natural Science Foundation of Hunan Province(2024JJ5184)+2 种基金the Hunan Provincial Science&Technology Major Project(2022sfq30,20231F18)the Key Projects of Hunan Provincial Education Department(23A0196)the Earmarked Fund for Hunan Agriculture Research System(HARS-07).
文摘Deamidation, a type of post-translational modification commonly considered a hallmark of protein“aging” and function decay, is increasingly recognized for its pivotal role in regulating biologicalprocesses and viral infection. Our previous study has demonstrated that the deamidation of replicationand transcription activator (RTA), a master regulator of ubiquitous and oncogenic Kaposi's sarcomaassociated herpesvirus (KSHV), mediated by phosphoribosylformylglycinamidine synthetase (PFAS),hinders its nuclear import and transcriptional activity. Here we report that the viral glutamine amidotransferase (vGAT) pseudo-enzyme is exploited to facilitate KSHV lytic infection by inhibiting RTAdeamidation. To be more specific, vGAT interacts with both RTA and cellular PFAS, and inhibits PFASmediated RTA deamidation, thus facilitating RTA nuclear localization and suppressing nuclear factorkappa B (NF-κB) signaling activation, as well as augmenting RTA-mediated transcriptional activationof viral open reading frames (ORFs). In addition, vGAT appears to regulate the deamidation process ofseveral viral ORFs of KSHV. Collectively, these findings unveil that a viral pseudo-enzyme is exploitedto enhance viral infection via deamidation regulation.
基金the National Natural Science Foundation of China (31871066, 31471065)the National Basic Research Development Program (973 Program) of China (2015CB559201)+2 种基金the Thousand Young Talents Program of Chinathe Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32010200)as part of the Chinese Academy of Science interdisciplinary innovation team
文摘Adult male mice emit highly complex ultrasonic vocalizations(USVs)in response to female conspecifics.Such US Vs,thought to facilitate courtship behaviors,are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism.While the regulation of US Vs by genetic factors has been extensively characterized,the neural mechanisms that control USV production remain largely unknown.Here,we report that optogenetic activation of the medial preoptic area(mPOA)elicited the production of USVs that were acoustically similar to courtship US Vs in adult mice.Moreover,mPOA vesicular GABA transporter-positive(Vgat +)neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons.Furthermore,ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males.Together,these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.
