Plasticity of excitatory and inhibitory synapses during pathology

A major focus of our lab is to understand how the coordinated plasticity of excitatory and inhibitory synapses is altered during different pathologies. In many brain disorders there is thought to be an imbalance between excitation and inhibition in key brain regions (eg. autism, schizophrenia, down syndrome). Therefore understanding how excitatory and inhibitory synapses function together to maintain the correct excitability of neurons and their circuits is essential to understand how these disorders develop. To study this we interrogate the plasticity of both excitatory and inhibitory synapses, and the function of a number of disease-associated proteins that are involved in synaptic function.We use a range of methods including advanced imaging, electrophysiology and biochemistry.  In particular we have a focus on using advanced live-confocal, glutamate uncaging, FRAP, FRET and super-resolution imaging techniques.

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The nanoscale composition of synapses

Another key area of research in the lab is to characterize the nanoscale changes that occur at synapses during plasticity and pathology.  My previous work has shown the nanoscale structure of synapses and the distribution of synapse-associated proteins is important for our understanding of synaptic function (Smith et al. 2014, Neuron). We utilize a range of super-resolution imaging techniques to further this goal (STED, STORM and SIM), combined with the development of novel computational methods to analyze data from super-resolution imaging modalities. Further, our lab is lucky to have its own super-resolution Structured Illumination Microscope (SIM) to fully explore the nanoscale structure of synapses and their associated proteins.