Vesicular neurotransmitter release and glutamate transporter function

Our research focuses on the details of fast synaptic transmission. Experiments in the lab incorporate a multidisciplinary approach of electrophysiological, imaging methods, and molecular biological approaches to study the activity of synapses and glutamate transporters. One model system that we use to study synaptic transmission and glutamate uptake are slices from cerebellum.
Stacks Image 477
1) The cerebellum is responsible for coordinated skilled movements and the control of muscle tone. The functional output of the cerebellum is through Purkinje cells. Each Purkinje cell receives excitatory input from thousands of parallel fibers and a single climbing fiber. These excitatory synapses are isolated from one another by Bergmann glia membranes that express a high density of glutamate transporters. In addition, glutamate released into the synaptic cleft is cleared via transporters found on the postsynaptic Purkinje cells. By recording and imaging Purkinje cells and Bergmann glia, we study how transporters can influence the strength of synaptic signals and regulate the signal transduction pathways underlying cerebellar long-lasting plasticity. We are also using computer models and heterologous expression systems to study the biophysical properties of these molecules. By combining these methods, we aim to better understand glutamate transporters and their physiological roles in normal and pathological states.
Stacks Image 480
2) The activity of individual neurons make up the basic unit of neuronal circuit behavior. This activity is dependent on the rules that each neuron uses to integrate synaptic inputs. Knowledge of the temporal properties of synaptic transmission is required to understand synaptic integration. We aim to study how the mechanisms of synaptic transmission and the regulation of vesicular fusion affect Purkinje cell integration and firing properties. This will lead to a basis for understanding the cerebellar functional output that may be affected in motor disorders and disorders of learning and memory. The regulation of synaptic timing by vesiclular release may be a mechanism for refining temporal signaling throughout the nervous system.