Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MG^A1 neurons) in resilient mice. In addition, this temporal neural plasticity of MG^A1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF–TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MG^A1 neurons, rather than merely activating MG^A1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.

当从逆境中恢复过来时，韧性可以使个人具有心理弹性。在这项研究中，我们确定了在自然恢复力中发挥作用的微电路和相关分子适应。我们发现来自同侧内侧膝状体 (MG) 的丘脑输入激活初级听觉皮层 (A1) 中的小清蛋白 (PV) 中间神经元对于暴露于慢性社交失败压力的小鼠的恢复力至关重要。慢性社交失败压力期间的早期攻击导致 MG 神经元短期超极化，投射到弹性小鼠的A1（MG ^{A1神经元）。}此外，MG ^{A1的这种时间神经可塑性}神经元通过突触前 BDNF-TrkB 信号在随后的应激反应中启动丘脑 PV 神经元的突触发生。^{此外，光遗传学模拟 MG A1}神经元的短期超极化，而不是仅仅激活 MG ^A1神经元，引发了应对压力的先天弹性机制，并在多种动物模型中实现了持续的抗抑郁样作用，代表了靶向神经调节的新策略.