Wade Regehr, Ph.D.

Professor of Neurobiology

Harvard Medical School
Dept of Neurobiology
220 Longwood Ave
Boston, MA 02115
Telephone: 617-432-0435
Fax: 617- 734-7557
Email: wade_regehr@hms.harvard.edu

Our 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, including retrograde signaling by endocannabinoids.  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. In recent years we have begun to study small circuits.

Most of the studies have been performed on synapses in the cerebellum, which are well described anatomically, accessible and relatively easy to study. Many studies are also performed within the LGN at synapses between retinal ganglion cells, local interneurons that can release GABA from their dendrites, and thalamic relay neurons. The primary experimental approaches are 2 photon imaging of calcium, electrophysiological measurements, and the manipulation of cell firing with channelrhodopsin-2. These studies will be augmented by serial electron microscopy, array tomography, in vivo studies, the development of transgenic mice and behavior.  

References:

• Abbott LF, Regehr WG (2004) Synaptic computation. Nature 431: 796-803. 
• Safo PK, Regehr WG (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48: 647-659.
• Brenowitz SD, Regehr WG (2005) Associative short-term synaptic plasticity mediated by endocannabinoids. Neuron 45: 419-431.
• Beierlein M, Fioravante D, Regehr WG (2007) Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity. Neuron 54: 949-959.
• Acuna-Goycolea C, Brenowitz SD, Regehr WG (2008) Active Dendritic Conductances Dynamically Regulate GABA Release from Thalamic Interneurons. Neuron 57: 420-431.
• Carey MR, Regehr WG (2009) Noradrenergic control of associative synaptic plasticity by selective modulation of instructive signals. Neuron 62: 112-122.
• Best AR, Regehr WG (2009) Inhibitory regulation of electrically coupled neurons in the inferior olive is mediated by asynchronous release of GABA. Neuron 62: 555-56.
• Myoga MH, Beierlein M, Regehr WG (2009) Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials. J Neurosci 29: 7803-7814.

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