Ricerc@Sapienza

The relationship existing between stress and development of psychopathologies is widely studied as psychiatric disorders, including depression, affect large numbers of people worldwide. Luckily, not all individuals are equally affected by exposure to aversive events, indicating a role for the interplay between genetic and environmental factors in determining the behavioural outcome. We have previously shown that the RCF manipulation (a stressing disruption of the newborn-mother relationship) of C57 females induces pro-resilience behavior in adults via a long-lasting reduction of both hyperpolarization-activated (Ih) current and evoked cell excitability in identified DAergic neurons of the intermediate VTA (D'Addario et al., 2021). Here, we aim to expand our research and show that, in a mirrored way, the susceptibility to depression shown by adult DBA RCF females is paralleled by a potentiation of both Ih current and cell excitability in those neurons. We also predict that DBA males will lack such alterations, as they are unaffected by RCF. Last, we want to investigate whether the long-lasting modulation of DAergic neurons equally affects all VTA neurons, or, rather, is induced in a cell/area-selective manner. To do so, we will adopt a multidisciplinary approach based on the use of behavioral tests, slice patch-clamp recording, in vivo intraVTA infusion of drugs and retrograde labelling / mapping of VTA neurons. We hope that our studies will help demonstrating that the long-term (epigenetic) modulation of the electrophysiological profile of TH+ neurons of the intermediate VTA represents the `crosslink between post-natal stressing experience and development of resilience/depression in adulthood of individuals with different genetic background.