Wade Regehr

Wade Regehr, PhD

Bullard Professor of Neurobiology

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.

regehr researchExperimental 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."

Publications View
Introduction of synaptotagmin 7 promotes facilitation at the climbing fiber to Purkinje cell synapse.
Authors: Authors: Weyrer C, Turecek J, Harrison B, Regehr WG.
Cell Rep
View full abstract on Pubmed
Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex.
Authors: Authors: Guo C, Rudolph S, Neuwirth ME, Regehr WG.
Elife
View full abstract on Pubmed
Presynaptic short-term plasticity persists in the absence of PKC phosphorylation of Munc18-1.
Authors: Authors: Wang CC, Weyrer C, Fioravante D, Kaeser PS, Regehr WG.
J Neurosci
View full abstract on Pubmed
Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.
Authors: Authors: Turecek J, Regehr WG.
Elife
View full abstract on Pubmed
Cerebellum-Specific Deletion of the GABAA Receptor d Subunit Leads to Sex-Specific Disruption of Behavior.
Authors: Authors: Rudolph S, Guo C, Pashkovski SL, Osorno T, Gillis WF, Krauss JM, Nyitrai H, Flaquer I, El-Rifai M, Datta SR, Regehr WG.
Cell Rep
View full abstract on Pubmed
Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.
Authors: Authors: Han KS, Chen CH, Khan MM, Guo C, Regehr WG.
Nat Neurosci
View full abstract on Pubmed
Meissner corpuscles and their spatially intermingled afferents underlie gentle touch perception.
Authors: Authors: Neubarth NL, Emanuel AJ, Liu Y, Springel MW, Handler A, Zhang Q, Lehnert BP, Guo C, Orefice LL, Abdelaziz A, DeLisle MM, Iskols M, Rhyins J, Kim SJ, Cattel SJ, Regehr W, Harvey CD, Drugowitsch J, Ginty DD.
Science
View full abstract on Pubmed
Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions.
Authors: Authors: Khan MM, Regehr WG.
Elife
View full abstract on Pubmed
Cerebellar Purkinje cell activity modulates aggressive behavior.
Authors: Authors: Jackman SL, Chen CH, Offermann HL, Drew IR, Harrison BM, Bowman AM, Flick KM, Flaquer I, Regehr WG.
Elife
View full abstract on Pubmed
Diverse roles of Synaptotagmin-7 in regulating vesicle fusion.
Authors: Authors: Huson V, Regehr WG.
Curr Opin Neurobiol
View full abstract on Pubmed