We review the experimental and computational data about the propagation of neural signals in myelinated axons in mice,cats,rabbits,and frogs published in the past five decades.In contrast to the natural assumption tha...We review the experimental and computational data about the propagation of neural signals in myelinated axons in mice,cats,rabbits,and frogs published in the past five decades.In contrast to the natural assumption that neural signals occur one by one in time and in space,we figure out that neural signals are highly overlapped in time between neighboring nodes.This phenomenon was occasionally illustrated in some early reports,but seemed to have been overlooked for some time.The shift in time between two successive neural signals from neighboring nodes,defined as relay timeτ,was calculated to be only 16.3μs-87.0μs,i.e.,0.8%-4.4%of the average duration of an action potential peak(roughly 2 ms).We present a clearer picture of the exact physical process about how the information transmits along a myelinated axon,rather than a whole action potential peak,what is transmitted is only a rising electric field caused by transmembrane ion flows.Here in the paper,τrepresents the waiting time until the neighboring node senses an attenuated electric field reaching the threshold to trigger the open state.The mechanisms addressed in this work have the potential to be universal,and may hold clues to revealing the exact triggering processes of voltage-gated ion channels and various brain functions.展开更多
Neutrophil trafficking during inflammation is a highly orchestrated process,coordinating neutrophil recruitment,sterilization of the wound,and inflammation resolution.Although the chemotactic signals guiding neutrophi...Neutrophil trafficking during inflammation is a highly orchestrated process,coordinating neutrophil recruitment,sterilization of the wound,and inflammation resolution.Although the chemotactic signals guiding neutrophil recruitment to sites of inflammation are relatively well understood,our knowledge of mechanisms controlling cessation of neutrophil recruitment and return to normal tissue physiology remains incomplete.To gain insights into these processes,we designed a microfluidic device with an array of chemoattractant reservoirs,which mimics the microenvironment in infected tissues,when multiple clusters of microbes are present.We monitored the temporal dynamics of neutrophil recruitment toward the chemoattractant reservoirs at single cell resolution,for 3 h.We observed robust neutrophil recruitment that reached a plateau after 1.5 h,despite the continuous presence of strong chemoattractant gradients around the reservoirs.The timing of the plateau was dependent on the geometry of the devices and was independent from the number of neutrophils.On the basis of these observations,we ruled out sub-population sensitivity,chemoattractant scavenging,and production of a self-limiting stop signal as potential mechanisms underpinning the plateau in neutrophil recruitment.We found a strong correlation between the temporal stabilization of concentration changes and the plateau in neutrophils recruitment.These results suggest that dynamic aspects of chemoattractant gradients are key for maximizing recruitment during the acute phase of infections and limiting the accumulation of neutrophils as soon as the infection is contained.展开更多
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2017YFA0701302 and 2016YFA0200802)the Fundamental Research Funds of Shandong University,China(Grant No.2018GN030)。
文摘We review the experimental and computational data about the propagation of neural signals in myelinated axons in mice,cats,rabbits,and frogs published in the past five decades.In contrast to the natural assumption that neural signals occur one by one in time and in space,we figure out that neural signals are highly overlapped in time between neighboring nodes.This phenomenon was occasionally illustrated in some early reports,but seemed to have been overlooked for some time.The shift in time between two successive neural signals from neighboring nodes,defined as relay timeτ,was calculated to be only 16.3μs-87.0μs,i.e.,0.8%-4.4%of the average duration of an action potential peak(roughly 2 ms).We present a clearer picture of the exact physical process about how the information transmits along a myelinated axon,rather than a whole action potential peak,what is transmitted is only a rising electric field caused by transmembrane ion flows.Here in the paper,τrepresents the waiting time until the neighboring node senses an attenuated electric field reaching the threshold to trigger the open state.The mechanisms addressed in this work have the potential to be universal,and may hold clues to revealing the exact triggering processes of voltage-gated ion channels and various brain functions.
基金This work was supported by grants from the National Institute of General Medical Sciences(GM092804)National Institute of Allergy and Infectious Diseases(AI113937)and Shriners Hospital for Children.Microfabrication was conducted at the BioMEMS Resource Center at Massachusetts General Hospital,supported by a grant from the National Institute of Biomedical Imaging and Bioengineering(EB002503).
文摘Neutrophil trafficking during inflammation is a highly orchestrated process,coordinating neutrophil recruitment,sterilization of the wound,and inflammation resolution.Although the chemotactic signals guiding neutrophil recruitment to sites of inflammation are relatively well understood,our knowledge of mechanisms controlling cessation of neutrophil recruitment and return to normal tissue physiology remains incomplete.To gain insights into these processes,we designed a microfluidic device with an array of chemoattractant reservoirs,which mimics the microenvironment in infected tissues,when multiple clusters of microbes are present.We monitored the temporal dynamics of neutrophil recruitment toward the chemoattractant reservoirs at single cell resolution,for 3 h.We observed robust neutrophil recruitment that reached a plateau after 1.5 h,despite the continuous presence of strong chemoattractant gradients around the reservoirs.The timing of the plateau was dependent on the geometry of the devices and was independent from the number of neutrophils.On the basis of these observations,we ruled out sub-population sensitivity,chemoattractant scavenging,and production of a self-limiting stop signal as potential mechanisms underpinning the plateau in neutrophil recruitment.We found a strong correlation between the temporal stabilization of concentration changes and the plateau in neutrophils recruitment.These results suggest that dynamic aspects of chemoattractant gradients are key for maximizing recruitment during the acute phase of infections and limiting the accumulation of neutrophils as soon as the infection is contained.