Sheriar

Biography

Sheriar Hormuzdi obtained a PhD from the Ohio State University, USA, and undertook postdoctoral research positions with Paul Bornstein (University of Washington, Seatle) and Hannah Monyer (Heidelberg University, Germany) before being awarded a Research Councils UK academic fellowship to continue research on electrical synapses in 2005.

Research Interest

Gap junctions, comprising intercellular channels composed of connexin (Cx) and pannexin (Px) proteins, provide a pathway for the passage of ions, secondary messenger molecules, and metabolites, thereby organizing an ensemble of cells into a biochemically- and electrically-coupled syncytium. Their importance is implied from the presence of 20 human connexin genes with different temporal and spatial expression patterns, and is evident from the phenotypes of mouse connexin knockouts and of inherited connexin disorders in humans. In neurons, gap junctions form the structural underpinnings of electrical synapses. Dual-cell recording experiments that reveal gap junction-mediated voltage responses have highlighted the unique ability of these structures to coordinate hyperpolarizing and depolarizing responses in connected cells with a high temporal precision. These features make them particularly suited for influencing excitability and action potential probability, and for synchronizing neuronal discharges and mediating oscillations - the rhythmic activity of large neuronal populations thought to be a means by which neurons are selected for further joint processing. Such population activity has been linked to behavioural states and is altered in a variety of neuyrological diseases like epilepsy, leading to the speculation that electrical synapses may underlie brain function and dysfunction. Indeed, recent studies on mice deficient in Cx36, a major component of electrical synapses, have indicated that the protein is required for synchrony in large neuronal networks, and for normal circadian activity, motor-coordination, and memory recall - conclusively demonstrating that coupling of neurons by a gap junction protein is important for the emergence of activity patterns and behaviour. While the above studies have gained recognition for the importance of gap junction-mediated communication in neurons and have indicated that electrical synapses are more prevalent than previously suspected, they also suggest that the distribution of electrical synapses in individual circuits is very specific, and have drawn attention to the paucity of information on the physiological and functional consequences of electrical synapses in individual neural systems. Determining the significance of electrical synapses and identifying the mechanisms that lead to a neuron-specific distribution of electrical synapses are my general research goals. My research employs biochemical, electrophysiological, cell biological, and molecular approaches and utlilizes animal models and stereotaxic delivery of viral constructs to determine electrical synaptic circuitry and function in the normal and pathological brain.