Development of functional neuronal networks

We are interested in understanding the process of information transfer at the chemical synapse and its relation to neuronal output. A large part of our work in this area focuses on understanding how neurotransmitter is released at individual presynaptic boutons and how they subsequently activate postsynaptic receptors. To tackle these questions we make use of fluorescent genetically-encoded probes that provide a functional readout of calcium, vesicle recycling, glutamate release and voltage, together with super-resolution microscopy to probe synapse structure at the nanoscale. Our aim is to combine the highly sensitive synaptic reporters currently available to characterize pre- and postsynaptic function at the level of a single synapse and, more globally, along an entire dendritic structure. Together with readouts of synaptic output (elecrohpysiology and voltage indicators), we hope to understand how the spatiotemporal integration of synaptic inputs onto a neuron controls its output.

A central question in neuroscience is to understand the wiring of the brain: how do neurons form synaptic connections and how do they develop into the mature structures found in adult brains? This question is particularly important in light of the recent evidence for a link between the process of synapse formation/maturation and neurodevelopmental disorders. We use a combination of different genetically-encoded reporters of both neuronal structure and function, together with serial block-face scanning electron microscopy, to follow the evolution of a synapse throughout the process of synaptogenesis and to provide a systematic map of the spatial distribution of excitatory and inhibitory inputs across a neuron. Our aim is to be able to image the gradual development of synapses at multiple spatial scales, from single synapses to entire dendritic maps of excitation and inhibition, and follow their maturation and modification by neuronal activity.