The relationship between dendritic spikes and synaptic development (360G-Wellcome-109302_Z_15_A)

Synaptic maturation and plasticity are essential for the establishment and refinement of neuronal circuits in the brain. Studies showing that dendritic excitability actively contributes to neuronal computation has redefined the classical concept of dendrites being passive electrical cables. Local NMDA-mediated dendritic spikes have been shown to alter synaptic plasticity and are associated with local rises in calcium concentration. Therefore, NMDA-mediated events are likely to influence the strength of the synapses, further underlying the importance of these receptors during synapse formation and information processing. However, these events have not been studied during brain development. Therefore, this research project aims to investigate the emergence of local dendritic NMDA-dependent spikes during development in vivo and in vitro in mice using electrophysiological techniques and calcium imaging. Our main goal is to understand whether these events drive synaptic formation and maturation or whether they require mature synapses to occur. We will both induce and block NMDA-spikes and observe the effects on synaptic maturation. Using sensory-deprived animals, the experience-dependency of these dendritic spikes will also be assessed. Furthermore, a knock-in mouse line of PSD95-eGFP, a major postsynaptic scaffolding protein, will be used to examine whether this protein is a marker for synaptic maturation.