Developmentally distinct architectures in top-down circuits.
Developmentally distinct architectures in top-down circuits.
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自上而下电路中发展独特的架构。
DOI：
10.1101/2023.08.27.555010
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
DeNardo,LauraA
中科院分区：
文献类型：
--
作者：
Klune,CassandraB;Goodpaster,CaitlinM;Gongwer,MichaelW;Gabriel,ChristopherJ;Chen,Rita;Jones,NicoS;Schwarz,LindsayA;DeNardo,LauraA
内侧前额叶皮质(MPFC)在学习、情绪和决策中发挥着关键作用，包括在个体如何应对威胁方面--。MPFC经历了一个独特的旷日持久的发展过程，突触密度、皮质厚度、远程连接和神经元编码特性的变化持续到成年早期。模型表明，在成年之前，发育缓慢的mPFC不能充分调节发育较快的皮质下中心的活动。他们提出，在发育过程中，皮质下系统的增强影响是青少年独特的行为策略的基础，增加对皮质下结构的mPFC控制最终允许成人行为的出现。然而，随着个人的成熟，逐步加强自上而下的控制如何导致行为的非线性变化仍不清楚。为了解决这种差异，我们在这里监测和操纵了动物对威胁做出反应时发育中的大脑活动，建立了前额边缘回路活动与幼年、青少年和成年小鼠行为策略之间的直接因果联系。我们没有线性地加强mPFC突触连接逐渐调节行为，而是在针对杏仁基底外侧核(BLA)和伏隔核(NAC)的mPFC回路的行为作用中发现了多个发育开关。我们表明，这些变化伴随着轴突修剪，同时mPFC-BLA和mPFC-NAC通路的突触连接功能得到加强，这两条通路以不同的速度成熟。我们的结果揭示了开发mPFC电路如何通过不同的体系结构，使它们能够最佳地适应特定年龄挑战的需求。
The medial prefrontal cortex (mPFC) plays a key role in learning, mood and decision making, including in how individuals respond to threats–. mPFC undergoes a uniquely protracted development, with changes in synapse density, cortical thickness, long-range connectivity, and neuronal encoding properties continuing into early adulthood–. Models suggest that before adulthood, the slow-developing mPFC cannot adequately regulate activity in faster-developing subcortical centers,. They propose that during development, the enhanced influence of subcortical systems underlies distinctive behavioural strategies of juveniles and adolescents and that increasing mPFC control over subcortical structures eventually allows adult behaviours to emerge. Yet it has remained unclear how a progressive strengthening of top-down control can lead to nonlinear changes in behaviour as individuals mature,. To address this discrepancy, here we monitored and manipulated activity in the developing brain as animals responded to threats, establishing direct causal links between frontolimbic circuit activity and the behavioural strategies of juvenile, adolescent and adult mice. Rather than a linear strengthening of mPFC synaptic connectivity progressively regulating behaviour, we uncovered multiple developmental switches in the behavioural roles of mPFC circuits targeting the basolateral amygdala (BLA) and nucleus accumbens (NAc). We show these changes are accompanied by axonal pruning coinciding with functional strengthening of synaptic connectivity in the mPFC-BLA and mPFC-NAc pathways, which mature at different rates. Our results reveal how developing mPFC circuits pass through distinct architectures that may make them optimally adapted to the demands of age-specific challenges.