All animals need to be resilient to perturbations in their internal and external environments. Mechanisms that ensure or promote resilience must exist on a large variety of time scales, from milliseconds to years for long-lived animals such as humans. Moreover, many psychiatric disorders may be expressed as a lack of resilience to a variety of stresses, so understanding the fundamental principles and cellular mechanisms that promote resilience in individuals and the population will provide a set of backbone concepts that will inform our understanding of the loss of resilience seen in mental illnesses. This computational/theoretical project will explore a number of hypotheses and potential mechanisms that may contribute to increasing the resilience of neurons and circuits to perturbation. Specific Aim #1 will explore the hypothesis that neurons with multiple voltage-dependent currents with overlapping properties will be more resilient to perturbation than neurons with fewer currents. Specific Aim #2 will characterize and explore the dynamic range of small reciprocally inhibitory circuits in response to perturbation. Of particular interest is whether resilience at one level of organization percolates to the next level. Specific Aim #3 will study a newly refined model of homeostatic tuning of intrinsic excitability and determine if homeostatic changes in response to a single, short-term perturbation result in changes of resilience towards repeat presentations of the same perturbation or qualitatively different perturbations. These studies may provide insight into how repeated insults “accrue” to produce long-term changes in mental health.