Wade Regehr, PhD

My long-term goal is to determine how presynaptic neurons influence the firing of their targets and to understand how physiologically significant computations are performed by synapses. Fast chemical synapses are the primary means of communication between neurons. They are constantly modified by a variety of mechanisms in ways that are vital to memory formation and normal brain function. With calcium implicated in almost every aspect of transmission, my focus has been on the many basic questions regarding calcium control of synaptic strength in the mammalian brain.

It is clear that many calcium dependent processes work together to control the release of neurotransmitter. These include synaptic facilitation, chemical messenger mediated release, depression and delayed release of neurotransmitter. My strategy has been to examine each of these mechanisms in isolation and then to determine how they interact to control synapses during realistic spike trains. Most of the studies have been performed on synapses in the cerebellum, which are well described anatomically, accessible and relatively easy to study. To explore the physiological relevance of various aspects of synaptic transmission we have recently started to study the synapse between retinal ganglion cells and thalamic relay neurons. In future years the primary experimental approaches will remain imaging of ionic levels within cells and electrophysiological measurements. It is anticipated, however, that these approaches will be augmented by 2-photon imaging with molecularly engineered indicators based on GFP.

Experimental arrangement for monitoring presynaptic calcium. A climbing fiber was labeled with a green calcium indicator and a Purkinje cell was labeled with a red dye.

"With calcium implicated in almost every aspect of transmission, my focus has been on the many basic questions regarding calcium control of synaptic strength in the mammalian brain."