It has long been observed that a subset of individuals within a population respond more favorably to stress than the rest of the population. This study aims to uncover the intrinsic molecular and cellular factors that modulate the protective effects toward a specific stressor: the toxic misfolding of the human α-synuclein protein, which is implicated in the degeneration of dopamine neurons in Parkinson’s Disease. Previously published work from our group has established that isogenic populations of the nematode C. elegans overexpressing α-synuclein from an integrated transgene exhibit reproducible and progressive age-dependent dopaminergic neurodegeneration. By utilizing this model system, we hypothesized that genetic and epigenetic factors, along with downstream targets of these factors, can be discovered that relate to the resilience exhibited by select animals in combating the stress of α-synuclein in dopamine neurons more effectively than others. We have developed a trans-generational behavioral enrichment scheme whereby individuals that express α-synuclein in dopamine neurons are selected for resilience in the context of the Basal Slowing Response (BSR), a quantifiable readout associated with dopamine neuron dysfunction. Selective propagation of animals that exhibit a BSR more like wild-type across subsequent generations has yielded heritable enrichment that has been found to last through four or more generations, after which it resets to resemble the defective BSR that individuals expressing α-synuclein in dopamine neurons characteristically exhibit. Along with examining the degeneration of dopamine neurons in strains of C. elegans over-expressing candidate neuro-protective genes, as well as strains of C. elegans under-expressing these same genes via RNAi, a better understanding of the innate cellular mechanisms that resilient individuals employ to actively combat the stress of α-synuclein in dopamine neurons can be ascertained.