Mom matters: Expound the influence of the interaction between maternal 5-HTT genotype and maternal care on offspring’s individual neurodevelopment

Serotonin plays a prominent role in a wide range of psychiatric disorders.

Importantly, serotonin (5-HT) is not only a neurotransmitter but also a neurotrophic factor during brain development, contributing to neurodevelopmental disorders (NDDs).

One largely neglected source of 5-HT affecting development is maternal serotonergic genotype, which can influence offspring through the placenta and by changing maternal care behaviour.

As a pediatrician, I am interested in the latter, as it -unlike the biological route- can be modified, providing an opening for early intervention for children with NDDs.

Here, I will delineate for the first time how maternal serotonin transporter (5-HTT) genotype affects maternal care behaviour and impacts offspring development from an individual perspective.To understand the influence of maternal 5-HTT genotype on offsprings development related to sex and genotype, I will use the well-established 5-HTT knockout (5-HTT-/-) rat modeling 5-HTT gene variance in humans and affecting maternal care.

First, I will examine maternal care behaviours in wild-type and 5-HTT-/- mothers, and the developmental trajectories of male and female offspring with varying 5-HTT genotypes by tests assessing social and emotional behaviour from infancy to adulthood. Included are highly sophisticated analyzes of ultrasonic vocalizations, which I am an expert in.

Second, I will elucidate the offsprings brain-wide neuronal activity pattern using cutting-edge brain clearing and 3D lightsheet microscopy.

To test causality and provide a lead for an early intervention, I will determine if enrichment ameliorates maternal care and improves offspring development.

This project is expected to uncover how mother genotype influences offspring development in the context of behaviours relevant to NDDs and whether the developmental trajectory can be improved through a non-pharmacological intervention.