Stressful behavior is transferred epigenetically. Here we study the biophysical mechanism of such epigenetic inheritance. Mice were exposed to varying protocols of tone-shock fear conditioning: a predictable group exposed to repetitions of consistent pairs of tone-shock; an unpredictable group exposed to tone and shocks in a random order; a naïve control [MOU1] group exposed to home cage conditions. After two weeks, all groups were exposed to the tone only for three days. The unpredictable group exhibited significantly higher freezing than both control and predictable groups on all three days, pointing to an enhanced fear response and reduced extinction. This enhanced response was accompanied by reduced pots-burst after-hyperpolarization (AHP) amplitude in pyramidal neurons of the anterior insula. In the other hand, both unpredictable and predictable stress showed lower AHP amplitude in the Basolateral amygdala.Subjects of the three groups were paired for breeding, and first-generation offspring were exposed to one tone-mild shock pair followed by three days of tone-alone exposure. Offspring of both predictable and unpredictable subjects exhibited significantly higher freezing levels than offspring of naïve parents, with significantly higher responsiveness in offspring of the unpredictable group.Additionally, offspring of the unpredictable group were born with lower AHP amplitude in the anterior insula neurons.These results indicate that experiencing unpredictable stress can alter the neuronal properties of the insula's neurons and the behavioral response to fear. [MOU1]If you use ‘naïve’ in graphs use it here too.