Structural properties of fast glutamate signaling

Ionotropic glutamate receptors (iGluR) are ligand-gated ion channels that are fundamental to nearly all brain functions. A central determinant of iGluR function is opening of its ion channel in response to synaptic release of glutamate. We are interested in understanding the fundamental mechanisms coupling agonist binding to ion channel opening, and how, once the channel is open, ions including Ca2+ flow through the membrane. This work is done in collaboration with Dr. Huan-Xiang Zhou, a computational biologist, at the University of Illinois at Chicago.

NMDA receptors in brain development and circuits

NMDA receptors contribute broadly to the development of brain circuits and to a variety of behaviors. To study the role of NMDA receptors in health and disease, we use a model organism, zebrafish, where we can rapidly manipulate its genome. We are particularly interested in the role of NMDA receptors in circuits involved in visual processing and habituation. This work is being done in collaboration with Dr. Howard Sirotkin at Stony Brook University.

GABAergic signaling in circuit development

GABA subtype A receptors (GABAA receptors) are ligand-gated ion channels found throughout the central nervous system. In contrast to glutamate-gated ion channels, GABA-mediated channels mediate inhibition rather than excitation. The balance of excitation and inhibition is critical to the normal development of brain circuits. We are interested in defining how modulation of the GABAergic system by benzodiazepines early in development, as occurs in the clinic for premature infants, affects circuit maturation.

Dynamics of ribbon synapses in the retina [Continuation of work initiated by Gary G. Matthews]

Ribbon synapses carry out specialized function in sensory systems and share molecular features with conventional synapses. We are interested in understanding the basic mechanism of vesicle fusion and recycling and the specialized role ribbon synapses play in sensory dynamics. This work is done in collaboration with Dr. David Zenisek at Yale University.

Glutamate signaling in disease

Dysfunction of iGluRs, including the NMDA receptor subtype, are implicated in a variety of neurological and neuropsychiatric disorders. We are particularly interested in disorders caused by direct dysfunction of NMDA receptors, so-called channelopathies. We are focusing on two such channelopathies: auto-antibodies targeting the GluN2A and GluN2B subunits in Systemic Lupus Erythematosus (SLE) that are associated with neuropsychiatric and cognitive deficits and de novo missense mutations in NMDA receptor subunits associated with early-onset epilepsy. Our experiments with anti-GluN2 antibodies in lupus are done in collaboration with Dr. Betty Diamond at the Feinstein Institute, while our epilepsy studies are done in collaboration with Dr. Lou Manganas, a pediatric neurologist at Stony Brook University Hospital who specializes in epilepsy. 

Our labs are part of The Center for Nervous System Disorder

Basic insights today leading to the clinical solutions of tomorrow...

Other investigators include: 

• Simon Halegoua, Center Director

• Joshua Plotkin

• Roger Sher

• Markus Riessland

Affiliations

• Department of Neurobiology & Behavior

• Department of Biochemistry and Cell Biology

• Department of Surgery

• Neuroscience Institute