Synapses are believed to represent the computational units of the brain and synaptic plasticity is believed to underlie many essential brain functions including information processing. Yet, due to inaccessibility of most central synapses to conventional experimental techniques, many basic synaptic mechanisms and their computational significance remain elusive. Research in my laboratory is focused on understanding the mechanisms and regulation of neurotransmitter release in central synapses in healthy and disease conditions. Our second major interest is elucidating the functional roles of presynaptic processes in synaptic plasticity and information processing. We are currently developing three main projects to address these questions by:

1. Studying presynaptic release mechanisms and synaptic vesicle cycling at the level of individual synapses. Using super-resolution imaging techniques in combination with advanced image analysis and computational approaches we can simultaneously visualize movements and release of several vesicles inside a synapse. In parallel, we use high-resolution capacitance measurements to detect and study fusion of individual synaptic vesicles at active zones.

2. Investigating how presynaptic processes give rise to short-term plasticity and how this plasticity determines information processing by individual synapses and functional circuits. Using natural spike trains recorded in behaving rodents we extend this analysis from individual synapses to the circuit level, and investigate synaptic interactions in basic feed-forward and feed-back circuits.

3. Relating deregulation in synaptic mechanisms with the impairment of information processing observed in many developmental diseases, such as Fragile X syndrome. We use mouse model of Fragile X syndrome and a variety of imaging, electrophysiological, biochemical and behavioral approaches to analyze how synaptic function and plasticity in cortical and hippocampal neurons is affected in this disorder.

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