Synaptic Modulation Mediated by Hyperpolarization-Activated Ion Channels

University Of California-Berkeley, Berkeley CA

Investigators

Abstract

0075842 Zucker Neurons communicate by releasing chemical transmitters at synaptic contacts. This project will explore mechanisms by which a hormone, serotonin, regulates synaptic transmission at a neuromuscular junction in crayfish, a preparation that is particularly accessible to modern cell biological probes. Serotonin increases transmitter release by elevating the cyclic adenosine 5'-monophosphate (cAMP) concentration in nerve terminals, which activates a particular presynaptic ion channel referred to as Ih. We will explore the mechanism by which Ih influences transmitter release. We will look for roles for Ca2+ influx through Ih channels and connections to cytoskeletal proteins, because such proteins and Ca2+ are known to influence transmitter release. Ih channels also may mediate the induction of a long-term facilitation (LTF) of synaptic enhancement following presynaptic activity. We will establish whether there are for Ih and cytoskeletal proteins in LTF induction. Serotonergic modulation of transmission involves increasing the size of the presynaptic store of releasable transmitter; we will determine whether LTF works the same way. Finally, we plan to measure the spatio-temporal profile of changes in cAMP concentration accompanying serotonin action and LTF. Serotonergic regulation of synaptic transmission is a critical locus for control of complex behaviors such as learning and memory. Pharmacological modification of synapses and serotonergic pathways are increasingly used to treat a large variety of neurological and psychiatric disorders. This project provides the basic knowledge essential for the understanding of complex behaviors and the development of therapeutic strategies.