Ricerc@Sapienza

Clinical and preclinical studies have highlighted how exposure to aversive events during sensitive developmental periods increases the expression of several stress-related psychiatric disorders later in life, such as depression. However, fortunately only a limited proportion of people exposed to early life adversity develop depression, while other show potentiated resilience.
Why do some individuals become depressed when exposed to early stressful life events while others do not?
Critical early life experiences can have detrimental or beneficial effects on development depending on interaction between genetic and environmental factors.
Early experiences strongly impact the reward brain circuit, a system critically involved in processing of motivational stimuli. We have previously demonstrated that exposure to a postnatal stress (Repeated Cross Fostering (RCF)) induces in C57BL/6J (C57) female mice increased resilience to depression-like phenotype in adult life, as well as an altered response of the preFrontal Cortex-Nucleus Accumbens DA system (one of the most important targets of VTA DA neurons) to motivational stimuli.
Interestingly females of a different inbred strain, DBA2/J (DBA) show opposite behavioral and neurochemical patterns following RCF exposure, leading to increased vulnerability to depression in adults.
Our preliminary electrophysiological data show that resilience observed in RCF C57 animals is related to reduced neurons excitability of dopaminergic neurons in VTA. Based on these results, we predict to find an opposite electrophysiological profile (increased excitability) in VTA DA neurons of RCF DBA mice.
We will also use a pharmacological approach to revert the behavioral and electrophysiological phenotypes observed in both strains modulating excitability of dopaminergic VTA neurons.
The goal of this project is to investigate the role of VTA DA neurons in entering resilience or vulnerability to early stress-induced depression.