Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511.
Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut 06520-8001.
J Neurosci. 2020 Jul 22;40(30):5857-5870. doi: 10.1523/JNEUROSCI.0910-20.2020. Epub 2020 Jun 29.
The most dynamic period of postnatal brain development occurs during adolescence, the period between childhood and adulthood. Neuroimaging studies have observed morphologic and functional changes during adolescence, and it is believed that these changes serve to improve the functions of circuits that underlie decision-making. Direct evidence in support of this hypothesis, however, has been limited because most preclinical decision-making paradigms are not readily translated to humans. Here, we developed a reversal-learning protocol for the rapid assessment of adaptive choice behavior in dynamic environments in rats as young as postnatal day 30. A computational framework was used to elucidate the reinforcement-learning mechanisms that change in adolescence and into adulthood. Using a cross-sectional and longitudinal design, we provide the first evidence that value-based choice behavior in a reversal-learning task improves during adolescence in male and female Long-Evans rats and demonstrate that the increase in reversal performance is due to alterations in value updating for positive outcomes. Furthermore, we report that reversal-learning trajectories in adolescence reliably predicted reversal performance in adulthood. This novel behavioral protocol provides a unique platform for conducting biological and systems-level analyses of the neurodevelopmental mechanisms of decision-making. The neurodevelopmental adaptations that occur during adolescence are hypothesized to underlie age-related improvements in decision-making, but evidence to support this hypothesis has been limited. Here, we describe a novel behavioral protocol for rapidly assessing adaptive choice behavior in adolescent rats with a reversal-learning paradigm. Using a computational approach, we demonstrate that age-related changes in reversal-learning performance in male and female Long-Evans rats are linked to specific reinforcement-learning mechanisms and are predictive of reversal-learning performance in adulthood. Our behavioral protocol provides a unique platform for elucidating key components of adolescent brain function.
大脑在后脑发育期（儿童期到成年期之间的阶段）经历最活跃的发展。神经影像学研究观察到了青春期期间的形态和功能变化，人们相信这些变化有助于改善决策基础回路的功能。然而，支持这一假设的直接证据有限，因为大多数临床前决策模式不易转化为人类。在这里，我们开发了一种反转学习协议，用于快速评估 30 日龄大的幼鼠在动态环境中的适应性选择行为。使用计算框架阐明了在青春期和成年期发生变化的强化学习机制。使用横断面和纵向设计，我们提供了第一个证据，即在反转学习任务中的基于价值的选择行为在雄性和雌性长耳大仓鼠的青春期期间得到改善，并证明反转表现的增加是由于积极结果的价值更新发生了变化。此外，我们报告说，青春期的反转学习轨迹可靠地预测了成年期的反转表现。这种新颖的行为协议为进行决策的神经发育机制的生物学和系统水平分析提供了独特的平台。人们假设青春期发生的神经发育适应性是与年龄相关的决策改善的基础，但支持这一假设的证据有限。在这里，我们描述了一种使用反转学习范式快速评估青春期大鼠适应性选择行为的新型行为协议。使用计算方法，我们证明了雄性和雌性长耳大仓鼠反转学习表现的年龄相关变化与特定的强化学习机制有关，并且可以预测成年期的反转学习表现。我们的行为协议为阐明青春期大脑功能的关键组成部分提供了独特的平台。
