Department of Foundational Sciences and Humanities, Discipline of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Center for Neurobiology of Stress Resilience and Psychiatric Disorders, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Int J Mol Sci. 2020 Apr 24;21(8):3008. doi: 10.3390/ijms21083008.
Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses. Here, we tested the hypothesis that the extent of PFC inhibition of the BLA following fear learning is greater in adults than in adolescents, using anesthetized in vivo recordings to measure local field potentials (LFPs) evoked by stimulation of PFC or auditory thalamic (MgN) inputs to BLA. We found that BLA LFPs evoked by stimulation of MgN inputs were enhanced in adults following fear conditioning. Fear conditioning also led to reduced summation of BLA LFPs evoked in response to PFC train stimulation, and increased the capacity of PFC inhibition of MgN inputs in adults. These data suggest that fear conditioning recruits additional inhibitory capacity by PFC inputs to BLA in adults, but that this capacity is weaker in adolescents. These results provide insight into how the development of PFC inputs may relate to age differences in memory retention and persistence following aversive learning.
青春期的特点是更容易发展出恐惧和焦虑相关障碍。青少年还表现出更高的恐惧反应和厌恶学习，这些反应和学习对行为干预有抵抗力，这可能与支持恐惧学习的电路改变有关。这些特征与内侧前额叶皮层 (PFC) 对基底外侧杏仁核 (BLA) 的输入在青少年时期的持续发育有关，这些输入调节神经活动，并有助于恐惧反应的精细化。在这里，我们使用麻醉状态下的活体记录来测量 PFC 或听觉丘脑 (MgN) 刺激对 BLA 诱发的局部场电位 (LFP)，测试了以下假设：在恐惧学习后，PFC 对 BLA 的抑制程度在成年人中比在青少年中更大。我们发现，在恐惧条件反射后，刺激 MgN 输入诱发的 BLA LFP 在成年人中增强。恐惧条件反射还导致对 PFC 刺激反应的 BLA LFP 总和减少，并增加了成年人中 PFC 对 MgN 输入的抑制能力。这些数据表明，恐惧条件反射通过成年人的 PFC 输入招募了额外的抑制能力，但在青少年中这种能力较弱。这些结果提供了深入了解 PFC 输入的发育如何与厌恶学习后记忆保留和持久性的年龄差异有关。
