We use sophisticated imaging and electrophysiological approaches to investigate synaptic function. Our research program seeks to understand the mechanisms by which signal transduction pathways modulate neurotransmission and consequently, behavior. Much of our research is directed to understand the control of neurotransmitter release and we are particularly interested in presynaptic calcium signalling and its control of neurotransmission in normal physiology and aging. We also have a longstanding program to determine how G protein coupled receptor mechanisms control synaptic transmission and how calcium signaling and modulatory mechanisms control behavior. These include projects to understand locomotor behaviors coordinated by spinal pattern generators, developmental changes and neurodegenerative changes. We are also interested in how postsynaptic signaling contributes to diseases of the brain.
We maintain collaborations with laboratories across North America, including the Dubuc laboratory (Montreal), the Hamm Laboratory (Vanderbilt) and the Morgan laboratory (Marine Biological Laboratory. We also collaborate with a number of laboratories in the UIC Neuroscience community. Notably with the laboratories of Leon Tai, Ernesto Bongarzone, Chris Peters, Kuei Tseng and Orly Lazarov.
Research Projects
In the presynaptic terminal we have discovered, in collaboration with Dr Heidi Hamm's laboratory at Vanderbilt University, how G proteins interact with key components of the synaptic vesicle fusion machinery. We are particularly interested in the mechanisms by which Gβγ interacts with the core fusion apparatus - the SNARE complex - to mediate synaptic plasticity.
Our Lattice Light - Sheet Microscope (LLSM) provides an alternative, high speed, low excitation intensity 4D imaging technique, with the Z-plane limited by the coherently interfering Bessel Beam’s array thickness (~400nm). LLSM was designed by Dr. Eric Betzig at Janelia Farm Research Center to provide high spatio-temporal imaging biological systems using an adjustable light sheet at low photobleaching and photo-toxicity. Ultra-thin modulation of the lattice structure also allows for development of structured illumination intermediate resolution microscopy (SIM) and improvements to resolution may be made using adaptive optics.
We are developing a holographic imaging system for this microscope and other light sheet modalities based on FINCH imaging to enable extraction of phase information, increasing the resolution and to provide high-speed volumetric imaging solutions.
We are interested in local gating of command systems
Command neurons of the locomotor system in vertebrates provide output to Central Pattern generators throughout the spinal cord. Local activity of the central pattern generators can enhance or suppress this output depending on phase or stage of activity. In this way local circuits involved in behavior profoundly control their own inputs.
We study presynaptic calcium signaling in physiology and pathology
Presynaptic calcium transients evoke neurotransmitter release. These transients are evoked by action potentials, depolarization and the opening of voltage dependent calcum channels. Control of these signals, along with homeostatic control of calcium in presynaptic terminals is little understood. We seek to understand the physiology and pathology of these systems.
We study activity dependent synapse formation in healthy and diseased brains.
This work continues the important and groundbreaking work of Dr Akira Yoshii who sadly passed away from cancer in 2023.
We study how synapses regulate palmitoylation and depalmitoylation which underlie trafficking of synaptic proteins including PSD-95. Our work focuses on a depalmitoylation enzyme Palmitoyl-Protein Thioesterase 1 (PPT1), which is mutated in neurogenetic disorder Batten's disease. A second major focus is the tuberous sclerosis complex 1(Tsc1) gene, which mediates Brain Derived Neurotrophic Factor (BDNF) signaling and regulates protein synthesis. Defects in this gene cause tuberous sclerosis, a rare disease that affects several organ systems and neurological symptoms include seizures, mental retardation and autistic behaviors. In an effort to clarify the role of Tsc in this disease, we are altering expression levels of the Tsc-1 protein.We will study dysregulated synaptic plasticity and abnormal connectivity of brain regions and neuronal network activity in Tsc-1 mutant brain.