Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host def...Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult（removing offending factors）and restoring structure and function of the brain（establish homeostasis）.The timing of these protective functions of the immune response is vital,since chronic inflammation展开更多
Most conceptual and computational models assume that synaptic transmission is reliable, a simplification rarely substantiated by data. The functional consequences of the recruitment of high and low initial release pro...Most conceptual and computational models assume that synaptic transmission is reliable, a simplification rarely substantiated by data. The functional consequences of the recruitment of high and low initial release probability synapses on the reliability and precision of their postsynaptic targets are studied in a multi-compartmental model of a hippocampal CA1 pyramidal cell. We show that changes in the firing rate of CA3 afferent inputs (rate remapping) are not reflected in the firing rate of the CA1 cell but in the reliability and precise timing of some of its action potentials, suggesting that a signature of remapping may be found in the precise spike timing of CA1. Our results suggest that about half of the action potentials produced by a CA1 cell can potentially carry reliable information in their precise timing with about 25 ms precision, a time scale on the order of the gamma cycle. We show further that reliable events were primarily elicited by CA3 synapses in a state of low probability of release. Overall, our results suggest that the non-uniform distribution of initial release probabilities observed experimentally achieves an optimum yielding simultaneously high precision and high reliability, and allows large populations of CA3 synapses to contribute to the production of reliable CA1 spiking events.展开更多
There has been a surge of diagnosis of autism spectrum disorders （ASD） over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, res...There has been a surge of diagnosis of autism spectrum disorders （ASD） over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.展开更多
文摘Acquired neurological injuries initiate a pathological cascade of secondary injury processes,including inflammation,which continue for days to weeks following injury.Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult（removing offending factors）and restoring structure and function of the brain（establish homeostasis）.The timing of these protective functions of the immune response is vital,since chronic inflammation
文摘Most conceptual and computational models assume that synaptic transmission is reliable, a simplification rarely substantiated by data. The functional consequences of the recruitment of high and low initial release probability synapses on the reliability and precision of their postsynaptic targets are studied in a multi-compartmental model of a hippocampal CA1 pyramidal cell. We show that changes in the firing rate of CA3 afferent inputs (rate remapping) are not reflected in the firing rate of the CA1 cell but in the reliability and precise timing of some of its action potentials, suggesting that a signature of remapping may be found in the precise spike timing of CA1. Our results suggest that about half of the action potentials produced by a CA1 cell can potentially carry reliable information in their precise timing with about 25 ms precision, a time scale on the order of the gamma cycle. We show further that reliable events were primarily elicited by CA3 synapses in a state of low probability of release. Overall, our results suggest that the non-uniform distribution of initial release probabilities observed experimentally achieves an optimum yielding simultaneously high precision and high reliability, and allows large populations of CA3 synapses to contribute to the production of reliable CA1 spiking events.
文摘There has been a surge of diagnosis of autism spectrum disorders （ASD） over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.
