The Hey-Kyoung Lee Lab is interested in exploring the cellular and molecular changes that happen at synapses to allow memory storage. We use various techniques, including electrophysiological recording, biochemical and molecular analysis, and imaging, to understand the cellular and molecular changes that happen during synaptic plasticity. Currently, we are examining the molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems. In particular, we found that loss of vision elicits global changes in excitatory synaptic transmission in the primary visual cortex. Vision loss also triggers specific synaptic changes in other primary sensory cortices, which we postulate underlies sensory compensation in the blind. One of our main research goals is to understand the mechanisms underlying such cross-modal synaptic plasticity. We are also interested in elucidating the events that occur in diseased brains. In collaboration with other researchers, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.

Research in the Alfredo Kirkwood Laboratory is directed toward elucidating the basic mechanisms by which visual experience can modify cortical connections in the visual cortex and how those mechanisms are regulated. In visual cortical slices, we investigate two forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). These two forms of synaptic plasticity are currently the most comprehensive models of the elementary mechanisms underlying naturally occurring plasticity. We are currently focused on how synaptic inhibition and the action of neuromodulators regulate the induction of LTP and LTD during development. We hope to gain a better understanding of how naturally occurring plasticity is regulated.

The Lau Lab uses a combination of computational and experimental approaches to study the atomic and molecular details governing the function of protein complexes involved in intercellular communication. We study ionotropic glutamate receptors (iGluRs), which are ligand-gated ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. iGluRs are important in synaptic plasticity, which underlies learning and memory. Receptor dysfunction has been implicated in a number of neurological disorders.

The David Linden Laboratory has used both electrode and optical recording in cerebellar slice and culture model systems to explore the molecular requirements for induction and expression of these phenomena. Along the way, we discovered a new form of plasticity. In addition, we have expanded our analysis to include use-dependent synaptic and non-synaptic plasticity in the cerebellar output structure, the deep nuclei. Our investigations are central to understanding the cellular substrates of information storage in a brain area where the behavioral relevance of the inputs and outputs is unusually well defined. In addition, our investigations have potential clinical relevance for cerebellar motor disorders and for disorders of learning and memory generally.

The Laboratory of Richard L. Huganir is interested in the mechanisms that regulate synaptic transmission and synaptic plasticity. Our general approach is to study molecular and cellular mechanisms that regulate neurotransmitter receptors and synapse function. We are currently focusing our efforts on the mechanisms that underlie the regulation of the glutamate receptors, the major excitatory neurotransmitter receptors in the brain.

Research in the Shigeki Watanabe Lab focuses on the cellular and molecular characterizations of rapid changes that occur during synaptic plasticity. Our team is working to determine the composition and distribution of proteins and lipids in the synapse as well as understand how the activity alters their distribution. Ultimately, we seek to discover how the misregulation of protein and lipid compositions lead to synaptic dysfunction. Our studies make use of cutting-edge electron microscopy techniques in combination with biochemical and molecular approaches.

The Paul Worley Lab examines the molecular basis of learning and memory. In particular, we cloned a set of immediate early genes (IEGs) that are rapidly transcribed in neurons involved in information processing, and that are essential for long term memory. IEG proteins can directly modify synapses and provide insight into cellular mechanisms that support synapse-specific plasticity.

Epilepsy affects 1-3% of the population and can have a profound impact on general health, employment and quality of life. Medial temporal lobe epilepsy (MTLE) develops in some patients following head injury or repeated febrile seizures. Those affected may first suffer spontaneous seizures many years after the initial insult, indicating that the neural circuit undergoes a slow pathologic remodeling over the interim. There are currently no methods of preventing the development of MTLE. It is our goal to better understand the process in order to slow, halt, and ultimately reverse it. Our laboratory draws on electrophysiology, molecular biology, and morphology to study the contribution of dysregulated neurogenesis and newborn neuron connectivity to the development of MTLE. We build on basic research in stem cell biology, hippocampal development, and synaptic plasticity. We work closely with colleagues in the Institute for Cell Engineering, Neurology, Neurosurgery, Biomedical Engineering, and Radiology. As physician neuropathologists our grounding is in tissue alterations underlying human neurologic disease; using human iPSC-derived neurons and surgical specimens we focus on the pathophysiological processes as they occur in patients. By understanding changes in cell populations and morphologies that affect the circuit, and identifying pathologic alterations in gene expression that lead to the cell-level abnormalities, we hope to find treatment targets that can prevent the remodeling and break the feedback loop of abnormal activity > circuit change > abnormal activity.