The Levitan lab studies long-term regulation of electrical activity and the control of neuropeptide release. The former studies are focused on electrical remodeling that contributes to the actions of antipsychotic drugs in the midbrain and promotes arrhythmias in the heart. The latter is aimed at understanding how electrical activity alters release of transmitters that are important for controlling mood, behavior and sensation. These topics are related because channels support the electrical activity that triggers neurosecretion, while motion and fusion of secretory vesicles support transmitter release and delivery of channels to the plasma membrane.
On the channel front, the lab is exploring how antipsychotic drugs increase Kv4.3 K+ channel expression in dopamine neurons known to be important in cognition and reward. In parallel, Kv4.3 downregulation in cardiac myocytes induced by angiotensin receptors is studied because this effect is thought to promote arrhythmias and sudden death. The lab is also collaborating on studies of other K+ channels. For example, Kv2.1 channel effects on apoptosis and exocytosis have been described with Drs. Aizenman (Neurobiology, University Pittsburgh) and Lotan (Physiology and Pharmacology, Tel Aviv University).
Another project uses in vivo fluorescent imaging of green fluorescent protein (GFP) constructs in transgenic Drosophila nerve terminals to determine how patterned electrical activity controls neuropeptide release. By optically detecting vesicle motion and signal transduction, new mechanisms have been discovered that acutely regulate secretion (e.g. vesicle mobilization) and maintain nerve terminal function (capture of transiting vesicles). Future studies will incorporate photoactivatable proteins and multiphoton microscopy to probe how neurons produce activity-dependent changes in secretory activity.
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