The Role of Serotonin on Cortex Development

This project aims to improve the understanding of the interaction between early life stress and serotonergic signalling on brain development, which can potentially influence behaviour in later life and contribute to e.g. anxiety and depression. In particular it will study the novel hypothesis that prenatal stress (PNS) results in changes in the balance of serotonin (5HT) signalling via 5HT1A and 5HT7 receptors that affect neuronal development. Focus will be on the cerebral cortex as it is associated with the processing of sensory information, decision making, memory storage and executive functions.
The hypothesis is based on recent reports that have identified abnormalities in serotonin signalling during brain development as risk factors for the development of autism, schizophrenia, anxiety disorders and depression in humans. In animal studies, experimental manipulations of 5HT signalling during early development cause changes in the cerebral cortex architecture and behavioural changes in later life. Furthermore, preliminary data has shown that PNS significantly changes the effect of 5HT1A/7 receptor activation in cortical neuron growth, and that PNS can shift the balance of cortical 5HT1A and 5HT7 receptor expression.
The two main objectives of the project are:
To characterise the effects of 5HT1A and 5HT7 signalling on neuronal growth and synapse formation of the different cortical neuron types.
To study the effects of PNS on 5HT1A and 5HT7 signalling as a potential mechanism that mediates stress effects on cortical development.
Primary cortical cultures from non-stressed and stressed rat pups will be used as a model system. A combination of genetic (gene expression profiling, siRNA), immuncytochemical, pharmacological and electrophysiological techniques will be used to study the interactions between PNS, 5HT1A and 5HT7 signalling on cortical neuron growth, synapse formation and neuronal network function.