Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse functi...Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.展开更多
A circular thin plate is proposed for vibration attenuation,which is attached alternately by annular piezoelectric unimorphs with resonant shunt circuits.Two kinds of equal frequency resonant shunt circuits are design...A circular thin plate is proposed for vibration attenuation,which is attached alternately by annular piezoelectric unimorphs with resonant shunt circuits.Two kinds of equal frequency resonant shunt circuits are designed to achieve an integrated locally resonant(LR)band gap(BG) with a much smaller transmission factor:(1) the structure is arrayed periodically while the resonant shunt circuits are aperiodic;(2) the resonant shunt circuits are periodic while the structure is aperiodic.The transmission factor curve is calculated,which is validated by the finite element method.Dependences of the LR BG performance upon the geometric and electric parameters are also analyzed.展开更多
基金supported by NIH/NIMH grant R01MH111619(to SQ),R21AG078700(to SQ)Institute of Mental Health Research(IMHR,Level 1 funding,to SQ and DF)institution startup fund from The University of Arizona(to SQ)。
文摘Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.
基金Project supported by the National Natural Science Foundation of China(Nos.11272126,51435006,and 51421062)the Fundamental Research Funds for the Central Universities,HUST:2016JCTD114 and 2015TS121the Research Fund for the Doctoral Program of Higher Education of China(No.20110142120050)
文摘A circular thin plate is proposed for vibration attenuation,which is attached alternately by annular piezoelectric unimorphs with resonant shunt circuits.Two kinds of equal frequency resonant shunt circuits are designed to achieve an integrated locally resonant(LR)band gap(BG) with a much smaller transmission factor:(1) the structure is arrayed periodically while the resonant shunt circuits are aperiodic;(2) the resonant shunt circuits are periodic while the structure is aperiodic.The transmission factor curve is calculated,which is validated by the finite element method.Dependences of the LR BG performance upon the geometric and electric parameters are also analyzed.