The role of neurotransmitter release in synapse formation

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Neurons in the brain communicate with each other at specialised points of contact, synapses, where chemicals called neurotransmitters are released from one side and activate receptors on the other. A huge amount of work over many years has sought to understand how synapses are formed (and, often, eliminated) during development. This is now an increasingly relevant goal, as it is believed that many neurodevelopmental disorders, such as autism and schizophrenia, may result from disruptions to the process of synapse formation. Therefore, a greater understanding of these processes could lead to new biomarkers or even treatments for these disorders.This proposal focuses on the role of neuronal activity in synapse formation. It has long been understood that activity can determine whether synapses are maintained or eliminated after they have been formed. Our recently published work, together with new preliminary data, now suggests that a particular form of activity, namely spontaneous neurotransmitter release, may in fact operate earlier in development to drive synapse formation itself. Our goal in this study is to examine how two different forms of neurotransmitter release (that evoked by neuronal firing, and that occurring spontaneously) regulate the formation of, and ultimately numbers of, different types of mammalian central nervous system synapses.