From parents to offspring: Influence of approaching/avoidance parental phenotypes on progeny

Individuals are hardwired to approach pleasure and to avoid negative stimuli. Nonetheless, Approach/Avoidance (A/A) conflict arises when a situation elicits these two opposite drives, simultaneously. I selected three sub-populations of male and female mice based on their withdrawing, balanced or advancing response to an A/A conflict task (i.e., avoiding (AV), balancing (BA) and approaching (AP) mice). The neuronal substrates sustaining the selected phenotypes were investigated by immunofluorescence methods, focusing on the oxytocinergic modulation (OXT) of dopamine (DA) neurons via oxytocin receptors (OTR), in the ventral tegmental area (VTA). The behavioral consequences of parental phenotypes on the progenies were evaluated. I found that AP male mice were characterized by a greater number of VTA-DA neurons, enriched in OTR, compared to controls and the AP paternal phenotype was able to bias descendants’ behaviors. Indeed, the offspring of AP fathers were more approaching and faster at the A/A conflict task, more prone towards novel stimuli compared to the offspring of AV fathers, and less anxious compared to controls. Conversely, AV females were characterized by lower VTA-DA cell density compared to controls, but maternal phenotype did not impact offspring’s response to A/A conflict. Maternal phenotype effects on progenies were sex-specific, affecting response to novelty only in female offspring and anxiety levels only in males. Finally, no phenotype effect on spontaneous parental care was observed. On the contrary, AV paternal phenotype influenced pup-retrieval behaviors of fathers and, indirectly, of their female mates, when separated from their pups. Given abnormal A/A motivation has been recognized in several psychological and psychiatric diseases, investigations on the mechanisms involved in A/A phenotype transmission and the development of transgenerational animal preclinical models are coveted.