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 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 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 MGA1 neurons, rather than merely activating MGA1 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. [Display omitted] • Primary auditory cortex (A1) parvalbumin interneurons activate in response to stress • Short-term hyperpolarization of A1-projecting thalamic neurons promotes resilience • Temporal neural plasticity initiates thalamic synaptogenesis via BDNF-TrkB signaling • Mimicking short-term hyperpolarization achieves sustained antidepressant-like effects In response to chronic social stress, A1 parvalbumin interneurons are activated by a short-term hyperpolarization of thalamic inputs that elicits BDNF-TrkB-dependent presynaptic synaptogenesis to promote resilience. [ABSTRACT FROM AUTHOR]