Wade Regehr

Illustration of the major elements in chemical synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the wave reaches a synapse, it provokes release of a puff of neurotransmitter molecules, which bind to chemical receptor molecules located in the membrane of another neuron, on the opposite side of the synapse.

Schematic of a chemical synapse between an axon of one neuron and a dendrite of another. Synapses are specialised minute gaps between neurons. The electrical impulses arriving at the axon terminal triggers the release of packets of chemical messengers (neurotransmitters), which diffuse across the synaptic cleft to receptors on the adjacent dendrite temporarily affecting the likelihood that an electrical impulse will be triggered in the latter neuron. Once released the neurotransmitter is rapidly metabolised or is pumped pack into a neuron.

Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. (A) Denotes Purkinje cells, an example of a bipolar neuron. (B) Denotes which are multipolar.

Wade G. Regehr is a Professor of Neurobiology at Harvard Medical School's Department of Neurobiology.^[1][2]

Early biography

Born in Shaunavon, Saskatchewan, Canada, Regehr attended the University of Regina in Canada, then received his Ph.D. at Caltech in applied physics with David Rutledge. His doctorate was at the interface between neuroscience and electrical engingeering.

Research

Regehr's laboratory studies the implication of calcium Ca²⁺ as it affects synaptic strength. Neurons communicate with one another via synapses. Regehr was one of the first to use fluorescent imaging to see the synaptic activity occurring in the brain. A dye alters the fluorenscence properties when attached to calcium, and changes in intracellular calcium are associated with neuronal activity (firing of action potentials). Using fluorescence-microscopy techniques, calcium levels are detected, and therefore the influx of calcium in the presynaptic neuron.^[3]

Calcium processes affect the release of neurotransmitter from the axon terminal. (Occasionally this happens in reverse).^[4]

Chemical synapses are characterized by the presynaptic release of neurotransmitters that diffuse across a synaptic cleft to bind with postsynaptic receptors. A neurotransmitter is a chemical messenger that is synthesized within neurons themselves and released by these same neurons to communicate with their postsynaptic target cells. By studying the physiological process and mechanisms, a further understanding is made of synaptic depression and delayed release of the neurotransmitter, synaptic potentiation, facilitation and other calcium dependent chemical processes.^[1]

Awards

Regehr received the Governor General's Award after receiving his undergraduate degree from the University of Regina. Regehr has been awarded the Senator Jacob Javits Award in the Neurosciences. This award provides funding for a possible seven years to research neurological disorders. The funding is provided by the National Institute of Neurological Disorders and Stroke (NINDS). Regehr's study of short term synaptic plasticity (synapse strength during behavioral tasks) is relevant to neurological disorders such as epilepsy, schizophrenia and depression.^[5]

Regehr also was granted a scholar award from The McKnight Endowment Fund for Neuroscience for The Role of Presynaptic Calcium in Plasticity at Central Synapses in 1993. The McKnight Scholar Awards are given to PhD candidates who have an interest in the study of disorders affecting learning and memory. The funding establishes laboratories for emerging neuroscientists who can develop clinical neuroscience research.^[6][7]

Selected articles

• Xu-Friedman Matthew A, Regehr Wade G (2008) Retrograde tuning of tuning. Neuron 2008;59(1):3-5.
• Best Aaron R; Regehr Wade G (2008) Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. The Journal of Neuroscience 2008;28(25):6508-15.
• Acuna-Goycolea Claudio; Brenowitz Stephan D; Regehr Wade G (2008) Active dendritic conductances dynamically regulate GABA release from thalamic interneurons. Neuron 2008;57(3):420-31.
• Safo Patrick; Regehr Wade G (2008) Timing dependence of the induction of cerebellar LTD. Neuropharmacology 2008;54(1):213-8.
• Brenowitz Stephan D; Regehr Wade G (2007) Reliability and heterogeneity of calcium signaling at single presynaptic boutons of cerebellar granule cells. Journal of Neuroscience 2007;27(30):7888-98.
• Beierlein Michael; Fioravante Diasynou; Regehr Wade G (2007) Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity. Neuron 2007;54(6):949-59.
• Crowley John J; Carter Adam G; Regehr Wade G (2007) Fast vesicle replenishment and rapid recovery from desensitization at a single synaptic release site. Journal of Neuroscience 2007;27(20):5448-60.
• Beierlein Michael; Regehr Wade G (2006) Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. Journal of Neuroscience 2006;26(39):9935-43.
• Beierlein Michael; Regehr Wade G (2006) Brief bursts of parallel fiber activity trigger calcium signals in bergmann glia. The Journal of Neuroscience 2006;26(26):6958-67.
• Brenowitz Stephan D; Best Aaron R; Regehr Wade G (2006) Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells. Journal of Neuroscience 2006;26(25):6841-50.
• Safo Patrick K; Cravatt Benjamin F; Regehr Wade G (2006) Retrograde endocannabinoid signaling in the cerebellar cortex. Cerebellum 2006;5(2):134-45.
• Foster Kelly A; Crowley John J; Regehr Wade G (2005) The influence of multivesicular release and postsynaptic receptor saturation on transmission at granule cell to Purkinje cell synapses. Journal of Neuroscience 2005;25(50):11655-65.
• Safo Patrick K; Regehr Wade G (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 2005;48(4):647-59.
• Xu-Friedman Matthew A; Regehr Wade G (2005) Dynamic-clamp analysis of the effects of convergence on spike timing. II. Few synaptic inputs. Journal of Neurophysiology 2005;94(4):2526-34.
• Xu-Friedman Matthew A; Regehr Wade G (2005) Dynamic-clamp analysis of the effects of convergence on spike timing. I. Many synaptic inputs. Journal of Neurophysiology 2005;94(4):2512-25.
• Beierlein Michael; Regehr Wade G (2005) Conventional synapses for unconventional cells. Neuron 2005;46(5):694-6.
• Blitz Dawn M; Regehr Wade G (2005) Timing and specificity of feed-forward inhibition within the LGN. Neuron 2005;45(6):917-28.
• Brenowitz Stephan D; Regehr Wade G (2005) Associative short-term synaptic plasticity mediated by endocannabinoids. Neuron 2005;45(3):419-31.
• Abbott L F; Regehr Wade G (2004) Synaptic computation. Nature 2004;431(7010):796-803.
• Blitz Dawn M; Foster Kelly A; Regehr Wade G (2004) Short-term synaptic plasticity: a comparison of two synapses. Nature Reviews Neuroscience 2004;5(8):630-40.
• Foster Kelly A; Regehr Wade G (2004) Variance-mean analysis in the presence of a rapid antagonist indicates vesicle depletion underlies depression at the climbing fiber synapse. Neuron 2004;43(1):119-31.
• Beierlein Michael; Gee Kyle R; Martin Vladimir V; Regehr Wade G (2004) Presynaptic calcium measurements at physiological temperatures using a new class of dextran-conjugated indicators. Journal of Neurophysiology 2004;92(1):591-9.
• Brown Solange P; Safo Patrick K; Regehr Wade G (2004) Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. Journal of Neuroscience 2004;24(24):5623-31.
• Xu-Friedman Matthew A; Regehr Wade G (2004) Structural contributions to short-term synaptic plasticity. Physiological Reviews 2004;84(1):69-85.
• Blitz Dawn M; Regehr Wade G (2003) Retinogeniculate synaptic properties controlling spike number and timing in relay neurons. Journal of Neurophysiology 2003;90(4):2438-50.
• Brown Solange P; Brenowitz Stephan D; Regehr Wade G (2003) Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nature Neuroscience 2003;6(10):1048-57.
• Brenowitz Stephan D; Regehr Wade G (2003) "Resistant" channels reluctantly reveal their roles. Neuron 2003;39(3):391-4.
• Brenowitz Stephan D; Regehr Wade G (2003) Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells. Journal of Neuroscience 2003;23(15):6373-84.
• Chen Chinfei; Regehr Wade G (2003) Presynaptic modulation of the retinogeniculate synapse. Journal of Neuroscience 2003;23(8):3130-5.
• Xu-Friedman Matthew A; Regehr Wade G (2003) Ultrastructural contributions to desensitization at cerebellar mossy fiber to granule cell synapses. Journal of Neuroscience 2003;23(6):2182-92.
• Kreitzer AC, Carter AG, Regehr WG (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34:787-796.
• Foster Kelly A; Kreitzer Anatol C; Regehr Wade G (2002) Interaction of postsynaptic receptor saturation with presynaptic mechanisms produces a reliable synapse. Neuron 2002;36(6):1115-26.
• Carter Adam G; Regehr Wade G (2003) Quantal events shape cerebellar interneuron firing. Nature Neuroscience 2002;5(12):1309-18.
• Kreitzer Anatol C; Regehr Wade G (2002) Retrograde signaling by endocannabinoids. Current Opinion in Neurobiology 2002;12(3):324-30.
• Kreitzer Anatol C; Carter Adam G; Regehr Wade G (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 2002;34(5):787-96.
• Chen Chinfei; Blitz Dawn M; Regehr Wade G (2002) Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. Neuron 2002;33(5):779-88.
• Carter Adam G; Vogt Kaspar E; Foster Kelly A; Regehr Wade G (2002) Assessing the role of calcium-induced calcium release in short-term presynaptic plasticity at excitatory central synapses. Journal of Neuroscience 2002;22(1):21-8.
• Zucker Robert S; Regehr Wade G (2002) Short-term synaptic plasticity. Annual Review of Physiology 2002;64():355-405.
• Kreitzer A C; Regehr W G (2001) Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. Journal of Neuroscience 2001;21(20):RC174.
• Xu-Friedman M A; Harris K M; Regehr W G (2001) Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells. Journal of Neuroscience 2001;21(17):6666-72.
• Kreitzer A C; Regehr W G (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 2001;29(3):717-27.
• Vogt K E; Regehr W G (2001) Cholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus. Journal of Neuroscience 2001;21(1):75-83.
• Chen C; Regehr W G (2000) Developmental remodeling of the retinogeniculate synapse. Neuron 2000;28(3):955-66.
• Xu-Friedman M A; Regehr W G (2000) Maximinis. Nature Neuroscience 2000;3(12):1229-30.
• Kreitzer A C; Gee K R; Archer E A; Regehr W G (2000) Monitoring presynaptic calcium dynamics in projection fibers by in vivo loading of a novel calcium indicator. Neuron 2000;27(1):25-32.
• Carter A G; Regehr W G (2000) Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. Journal of Neuroscience 2000;20(12):4423-34.
• Xu-Friedman M A; Regehr W G (2000) Probing fundamental aspects of synaptic transmission with strontium. Journal of Neuroscience 2000;20(12):4414-22.
• Dittman J S; Kreitzer A C; Regehr W G (2000) Interplay between facilitation, depression, and residual calcium at three presynaptic terminals. Journal of Neuroscience 2000;20(4):1374-85.
• Kreitzer A C; Regehr W G (2000)Modulation of transmission during trains at a cerebellar synapse. Journal of Neuroscience 2000;20(4):1348-57.
• Chen C; Regehr W G (1999) Contributions of residual calcium to fast synaptic transmission. Journal of Neuroscience 1999;19(15):6257-66.
• Xu-Friedman M A; Regehr W G (1999)Presynaptic strontium dynamics and synaptic transmission. Biophysical Journal 1999;76(4):2029-42.
• Sabatini B L; Regehr W G (1999) Timing of synaptic transmission. Annual Review of Physiology 1999;61():521-42.
• Atluri P P; Regehr W G (1998)Delayed release of neurotransmitter from cerebellar granule cells. Journal of Neuroscience 1998;18(20):8214-27.
• Dittman J S; Regehr W G (1998) Calcium dependence and recovery kinetics of presynaptic depression at the climbing fiber to Purkinje cell synapse. Journal of Neuroscience 1998;18(16):6147-62.
• Sabatini B L; Regehr W G (1998)Optical measurement of presynaptic calcium currents. Biophysical Journal 1998;74(3):1549-63.
• Dittman J S; Regehr W G (1997 Mechanism and kinetics of heterosynaptic depression at a cerebellar synapse. Journal of Neuroscience 1997;17(23):9048-59.
• Regehr W G (1997)Interplay between sodium and calcium dynamics in granule cell presynaptic terminals. Biophysical Journal 1997;73(5):2476-88.
• Chen C; Regehr W G (1997)The mechanism of cAMP-mediated enhancement at a cerebellar synapse. Journal of Neuroscience 1997;17(22):8687-94.
• Sabatini B L; Regehr W G (1997) Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. Journal of Neuroscience 1997;17(10):3425-35.
• Sabatini B L; Regehr W G (1996) Timing of neurotransmission at fast synapses in the mammalian brain. Nature 1996;384(6605):170-2.
• Atluri P P; Regehr W G (1996) Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse. Journal of Neuroscience 1996;16(18):5661-71.
• Dittman J S; Regehr W G (1996) Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse. Journal of Neuroscience 1996;16(5):1623-33.
• Tank D W; Regehr W G; Delaney K R (1995) A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement. Journal of Neuroscience 1995;15(12):7940-52.
• Sabatini B L; Regehr W G (1995) Detecting changes in calcium influx which contribute to synaptic modulation in mammalian brain slice. Neuropharmacology 1995;34(11):1453-67.
• Mintz I M; Sabatini B L; Regehr W G (1995) Calcium control of transmitter release at a cerebellar synapse. Neuron 1995;15(3):675-88.
• Regehr W G; Atluri P P (1995) Calcium transients in cerebellar granule cell presynaptic terminals. Biophysical Journal 1995;68(5):2156-70.
• Regehr W G; Tank D W (1994) Dendritic calcium dynamics. Current Opinion in Neurobiology 1994;4(3):373-82.
• Regehr W G; Armstrong C M (1994) Dendritic function. Where does it all begin? Current Biology 1994;4(5):436-9.
• Regehr W G; Mintz I M (1994) Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Neuron 1994;12(3):605-13.
• Regehr W G; Delaney K R; Tank D W (1994) The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse. Journal of Neuroscience 1994;14(2):523-37.
• Regehr W; Kehoe J S; Ascher P; Armstrong C (1993) Synaptically triggered action potentials in dendrites. Neuron 1993;11(1):145-51.
• Regehr W G; Tank D W (1992) Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells. Journal of Neuroscience 1992;12(11):4202-23.
• Regehr W G; Konnerth A; Armstrong C M (1992) Sodium action potentials in the dendrites of cerebellar Purkinje cells. Proceedings of the National Academy of Sciences of the United States of America 1992;89(12):5492-6.
• Regehr W G; Tank D W (1991) The maintenance of LTP at hippocampal mossy fiber synapses is independent of sustained presynaptic calcium. Neuron 1991;7(3):451-9.
• Regehr W G; Tank D W (1991) Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice. Journal of Neuroscience Methods 1991;37(2):111-9.
• Regehr W G; Tank D W (1990) Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CA1 pyramidal cell dendrites. Nature 1990;345(6278):807-10.
• Regehr W G; Pine J; Cohan C S; Mischke M D; Tank D W (1989) Sealing cultured invertebrate neurons to embedded dish electrodes facilitates long-term stimulation and recording. Journal of Neuroscience Methods 1989;30(2):91-106.
• Regehr W G; Connor J A; Tank D W (1989) Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation. Nature 1989;341(6242):533-6.
• Regehr W G; Pine J; Rutledge D B (1988) A long-term in vitro silicon-based microelectrode-neuron connection. IEEE Transactions on Bio-Medical Engineering 1988;35(12):1023-32.

See also

• Axon terminals

References