The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet ho...The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.展开更多
The fetal and infant origins of adult disease hypothesis proposed that the roots of adult chronic disease lie in the effects of adverse environments in fetal life and early infancy. In addition to the fetal period, fe...The fetal and infant origins of adult disease hypothesis proposed that the roots of adult chronic disease lie in the effects of adverse environments in fetal life and early infancy. In addition to the fetal period, fertilization and early embryonic stages, the critical time windows of epigenetic reprogramming, rapid cell differentiation and organogenesis, are the most sensitive stages to environmental disturbances. Compared with embryo and fetal development, gametogenesis and maturation take decades and are more vulnerable to potential damage for a longer exposure period. Therefore, we should shift the focus of adult disease occurrence and pathogenesis further back to gametogenesis and embryonic development events, which may result in intergenerational, even transgenerational, epigenetic re-programming with transmission of adverse traits and characteristics to offspring. Here, we focus on the research progress relating to diseases that originated from events in the gametes and early embryos and the potential epigenetic mechanisms involved.展开更多
基金This work was supported by the STI2030-Major Projects(2021ZD0203700/2021ZD0203703)the National Natural Science Foundation of China(31771151,32171030,and 32100829),the Lingang Lab(LG202104-01-03)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010200).
文摘The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
基金supported by Special Fund for the National Key Research and Development Plan (2017YFC1001303)National Natural Science Foundation of China (81490742 and 31571556)
文摘The fetal and infant origins of adult disease hypothesis proposed that the roots of adult chronic disease lie in the effects of adverse environments in fetal life and early infancy. In addition to the fetal period, fertilization and early embryonic stages, the critical time windows of epigenetic reprogramming, rapid cell differentiation and organogenesis, are the most sensitive stages to environmental disturbances. Compared with embryo and fetal development, gametogenesis and maturation take decades and are more vulnerable to potential damage for a longer exposure period. Therefore, we should shift the focus of adult disease occurrence and pathogenesis further back to gametogenesis and embryonic development events, which may result in intergenerational, even transgenerational, epigenetic re-programming with transmission of adverse traits and characteristics to offspring. Here, we focus on the research progress relating to diseases that originated from events in the gametes and early embryos and the potential epigenetic mechanisms involved.