Wade Regehr, Ph.D.

Professor of Neurobiology
  • Regehr Lab
  • 617/432-0435

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.

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.

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.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.

  1. Hull CA, Chu Y, Thanawala M, Regehr WG. Hyperpolarization induces a long-term increase in the spontaneous firing rate of cerebellar Golgi cells. April 3, 2013. The Journal of neuroscience : the official journal of the Society for Neuroscience.

    Link to Abstract
  2. Thanawala MS, Regehr WG. Presynaptic calcium influx controls neurotransmitter release in part by regulating the effective size of the readily releasable pool. March 13, 2013. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  3. Pressler RT, Regehr WG. Metabotropic glutamate receptors drive global persistent inhibition in the visual thalamus. February 6, 2013. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  4. Chu Y, Fioravante D, Thanawala M, Leitges M, Regehr WG. Calcium-dependent isoforms of protein kinase C mediate glycine-induced synaptic enhancement at the calyx of Held. October 3, 2012. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  5. Fioravante D, Myoga MH, Leitges M, Regehr WG. Adaptive regulation maintains posttetanic potentiation at cerebellar granule cell synapses in the absence of calcium-dependent PKC. September 19, 2012. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  6. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, Steinberg J, Crawley JN, Regehr WG, Sahin M. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. August 30, 2012. Nature.

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  7. Regehr WG. Short-term presynaptic plasticity. July 1, 2012. Cold Spring Harbor perspectives in biology.

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  8. Brenowitz SD, Regehr WG. Presynaptic imaging of projection fibers by in vivo injection of dextran-conjugated calcium indicators. April 1, 2012. Cold Spring Harbor protocols.

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  9. Hull C, Regehr WG. Identification of an inhibitory circuit that regulates cerebellar Golgi cell activity. January 12, 2012. Neuron.

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  10. Fioravante D, Chu Y, Myoga MH, Leitges M, Regehr WG. Calcium-dependent isoforms of protein kinase C mediate posttetanic potentiation at the calyx of Held. June 9, 2011. Neuron.

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  11. Myoga MH, Regehr WG. Calcium microdomains near R-type calcium channels control the induction of presynaptic long-term potentiation at parallel fiber to purkinje cell synapses. April 6, 2011. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  12. Fioravante D, Regehr WG. Short-term forms of presynaptic plasticity. February 23, 2011. Current opinion in neurobiology.

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  13. Carey MR, Myoga MH, McDaniels KR, Marsicano G, Lutz B, Mackie K, Regehr WG. Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses. November 17, 2010. Journal of neurophysiology.

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  14. Carey MR, Regehr WG. Phosphatase activity controls the ups and downs of cerebellar learning. August 26, 2010. Neuron.

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  15. Antal M, Acuna-Goycolea C, Pressler RT, Blitz DM, Regehr WG. Cholinergic activation of M2 receptors leads to context-dependent modulation of feedforward inhibition in the visual thalamus. April 6, 2010. PLoS biology.

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  16. Best AR, Regehr WG. Identification of the synthetic pathway producing the endocannabinoid that mediates the bulk of retrograde signaling in the brain. February 11, 2010. Neuron.

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  17. Crowley JJ, Fioravante D, Regehr WG. Dynamics of fast and slow inhibition from cerebellar golgi cells allow flexible control of synaptic integration. September 24, 2009. Neuron.

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  18. Kim JC, Cook MN, Carey MR, Shen C, Regehr WG, Dymecki SM. Linking genetically defined neurons to behavior through a broadly applicable silencing allele. August 13, 2009. Neuron.

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  19. Regehr WG, Carey MR, Best AR. Activity-dependent regulation of synapses by retrograde messengers. July 30, 2009. Neuron.

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  20. Myoga MH, Beierlein M, Regehr WG. Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials. June 17, 2009. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  21. Best AR, Regehr WG. Inhibitory regulation of electrically coupled neurons in the inferior olive is mediated by asynchronous release of GABA. May 28, 2009. Neuron.

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  22. Carey MR, Regehr WG. Noradrenergic control of associative synaptic plasticity by selective modulation of instructive signals. April 16, 2009. Neuron.

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  23. Xu-Friedman MA, Regehr WG. Retrograde tuning of tuning. July 10, 2008. Neuron.

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  24. Best AR, Regehr WG. Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. June 18, 2008. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  25. Acuna-Goycolea C, Brenowitz SD, Regehr WG. Active dendritic conductances dynamically regulate GABA release from thalamic interneurons. February 7, 2008. Neuron.

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  26. Brenowitz SD, Regehr WG. Reliability and heterogeneity of calcium signaling at single presynaptic boutons of cerebellar granule cells. July 25, 2007. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  27. Safo P, Regehr WG. Timing dependence of the induction of cerebellar LTD. June 26, 2007. Neuropharmacology.

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  28. Beierlein M, Fioravante D, Regehr WG. Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity. June 21, 2007. Neuron.

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  29. Crowley JJ, Carter AG, Regehr WG. Fast vesicle replenishment and rapid recovery from desensitization at a single synaptic release site. May 16, 2007. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  30. Beierlein M, Regehr WG. Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. September 27, 2006. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  31. Beierlein M, Regehr WG. Brief bursts of parallel fiber activity trigger calcium signals in bergmann glia. June 28, 2006. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  32. Brenowitz SD, Best AR, Regehr WG. Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells. June 21, 2006. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  33. Safo PK, Cravatt BF, Regehr WG. Retrograde endocannabinoid signaling in the cerebellar cortex. January 1, 2006. Cerebellum (London, England).

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  34. Foster KA, Crowley JJ, Regehr WG. The influence of multivesicular release and postsynaptic receptor saturation on transmission at granule cell to Purkinje cell synapses. December 14, 2005. The Journal of neuroscience : the official journal of the Society for Neuroscience.

    Link to Abstract
  35. Safo PK, Regehr WG. Endocannabinoids control the induction of cerebellar LTD. November 23, 2005. Neuron.

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  36. Xu-Friedman MA, Regehr WG. Dynamic-clamp analysis of the effects of convergence on spike timing. I. Many synaptic inputs. October 1, 2005. Journal of neurophysiology.

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  37. Xu-Friedman MA, Regehr WG. Dynamic-clamp analysis of the effects of convergence on spike timing. II. Few synaptic inputs. October 1, 2005. Journal of neurophysiology.

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  38. Beierlein M, Regehr WG. Conventional synapses for unconventional cells. June 2, 2005. Neuron.

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  39. Blitz DM, Regehr WG. Timing and specificity of feed-forward inhibition within the LGN. March 24, 2005. Neuron.

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  40. Brenowitz SD, Regehr WG. Associative short-term synaptic plasticity mediated by endocannabinoids. February 3, 2005. Neuron.

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  41. Abbott LF, Regehr WG. Synaptic computation. October 14, 2004. Nature.

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  42. Blitz DM, Foster KA, Regehr WG. Short-term synaptic plasticity: a comparison of two synapses. August 1, 2004. Nature reviews. Neuroscience.

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  43. Foster KA, Regehr WG. Variance-mean analysis in the presence of a rapid antagonist indicates vesicle depletion underlies depression at the climbing fiber synapse. July 8, 2004. Neuron.

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  44. Beierlein M, Gee KR, Martin VV, Regehr WG. Presynaptic calcium measurements at physiological temperatures using a new class of dextran-conjugated indicators. July 1, 2004. Journal of neurophysiology.

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  45. Brown SP, Safo PK, Regehr WG. Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. June 16, 2004. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  46. Xu-Friedman MA, Regehr WG. Structural contributions to short-term synaptic plasticity. January 1, 2004. Physiological reviews.

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  47. Blitz DM, Regehr WG. Retinogeniculate synaptic properties controlling spike number and timing in relay neurons. October 1, 2003. Journal of neurophysiology.

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  48. Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. September 21, 2003. Nature neuroscience.

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  49. Brenowitz SD, Regehr WG. "Resistant" channels reluctantly reveal their roles. July 31, 2003. Neuron.

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  50. Brenowitz SD, Regehr WG. Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells. July 16, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

    Link to Abstract
  51. Chen C, Regehr WG. Presynaptic modulation of the retinogeniculate synapse. April 15, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

    Link to Abstract
  52. Xu-Friedman MA, Regehr WG. Ultrastructural contributions to desensitization at cerebellar mossy fiber to granule cell synapses. March 15, 2003. The Journal of neuroscience : the official journal of the Society for Neuroscience.

    Link to Abstract
  53. Foster KA, Kreitzer AC, Regehr WG. Interaction of postsynaptic receptor saturation with presynaptic mechanisms produces a reliable synapse. December 19, 2002. Neuron.

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  54. Carter AG, Regehr WG. Quantal events shape cerebellar interneuron firing. December 1, 2002. Nature neuroscience.

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  55. Kreitzer AC, Regehr WG. Retrograde signaling by endocannabinoids. June 1, 2002. Current opinion in neurobiology.

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  56. Kreitzer AC, Carter AG, Regehr WG. Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. May 30, 2002. Neuron.

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  57. Chen C, Blitz DM, Regehr WG. Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. February 28, 2002. Neuron.

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  58. Carter AG, Vogt KE, Foster KA, Regehr WG. Assessing the role of calcium-induced calcium release in short-term presynaptic plasticity at excitatory central synapses. January 1, 2002. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  59. Zucker RS, Regehr WG. Short-term synaptic plasticity. January 1, 2002. Annual review of physiology.

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  60. Kreitzer AC, Regehr WG. Cerebellar depolarization-induced suppression of inhibition is mediated by endogenous cannabinoids. October 15, 2001. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  61. Xu-Friedman MA, Harris KM, Regehr WG. Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells. September 1, 2001. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  62. Kreitzer AC, Regehr WG. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. March 1, 2001. Neuron.

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  63. Vogt KE, Regehr WG. Cholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus. January 1, 2001. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  64. Chen C, Regehr WG. Developmental remodeling of the retinogeniculate synapse. December 1, 2000. Neuron.

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  65. Xu-Friedman MA, Regehr WG. Maximinis. December 1, 2000. Nature neuroscience.

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  66. Kreitzer AC, Gee KR, Archer EA, Regehr WG. Monitoring presynaptic calcium dynamics in projection fibers by in vivo loading of a novel calcium indicator. July 1, 2000. Neuron.

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  67. Xu-Friedman MA, Regehr WG. Probing fundamental aspects of synaptic transmission with strontium. June 15, 2000. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  68. Carter AG, Regehr WG. Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. June 15, 2000. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  69. Kreitzer AC, Regehr WG. Modulation of transmission during trains at a cerebellar synapse. February 15, 2000. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  70. Dittman JS, Kreitzer AC, Regehr WG. Interplay between facilitation, depression, and residual calcium at three presynaptic terminals. February 15, 2000. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  71. Chen C, Regehr WG. Contributions of residual calcium to fast synaptic transmission. August 1, 1999. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  72. Xu-Friedman MA, Regehr WG. Presynaptic strontium dynamics and synaptic transmission. April 1, 1999. Biophysical journal.

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  73. Sabatini BL, Regehr WG. Timing of synaptic transmission. January 1, 1999. Annual review of physiology.

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  74. Atluri PP, Regehr WG. Delayed release of neurotransmitter from cerebellar granule cells. October 15, 1998. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  75. Dittman JS, Regehr WG. Calcium dependence and recovery kinetics of presynaptic depression at the climbing fiber to Purkinje cell synapse. August 15, 1998. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  76. Sabatini BL, Regehr WG. Optical measurement of presynaptic calcium currents. March 1, 1998. Biophysical journal.

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  77. Dittman JS, Regehr WG. Mechanism and kinetics of heterosynaptic depression at a cerebellar synapse. December 1, 1997. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  78. Chen C, Regehr WG. The mechanism of cAMP-mediated enhancement at a cerebellar synapse. November 15, 1997. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  79. Regehr WG. Interplay between sodium and calcium dynamics in granule cell presynaptic terminals. November 1, 1997. Biophysical journal.

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  80. Sabatini BL, Regehr WG. Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. May 15, 1997. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  81. Connors BW, Regehr WG. Neuronal firing: does function follow form? December 1, 1996. Current biology : CB.

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  82. Sabatini BL, Regehr WG. Timing of neurotransmission at fast synapses in the mammalian brain. November 14, 1996. Nature.

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  83. Atluri PP, Regehr WG. Determinants of the time course of facilitation at the granule cell to Purkinje cell synapse. September 15, 1996. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  84. Dittman JS, Regehr WG. Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse. March 1, 1996. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  85. Tank DW, Regehr WG, Delaney KR. A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement. December 1, 1995. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  86. Sabatini BL, Regehr WG. Detecting changes in calcium influx which contribute to synaptic modulation in mammalian brain slice. November 1, 1995. Neuropharmacology.

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  87. Mintz IM, Sabatini BL, Regehr WG. Calcium control of transmitter release at a cerebellar synapse. September 1, 1995. Neuron.

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  88. Regehr WG, Atluri PP. Calcium transients in cerebellar granule cell presynaptic terminals. May 1, 1995. Biophysical journal.

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  89. Regehr WG, Tank DW. Dendritic calcium dynamics. June 1, 1994. Current opinion in neurobiology.

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  90. Regehr WG, Armstrong CM. Dendritic function. Where does it all begin? May 1, 1994. Current biology : CB.

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  91. Regehr WG, Mintz IM. Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. March 1, 1994. Neuron.

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  92. Regehr WG, Delaney KR, Tank DW. The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse. February 1, 1994. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  93. Regehr W, Kehoe JS, Ascher P, Armstrong C. Synaptically triggered action potentials in dendrites. July 1, 1993. Neuron.

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  94. Regehr WG, Tank DW. Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells. November 1, 1992. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  95. Regehr WG, Konnerth A, Armstrong CM. Sodium action potentials in the dendrites of cerebellar Purkinje cells. June 15, 1992. Proceedings of the National Academy of Sciences of the United States of America.

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  96. Garyantes TK, Regehr WG. Electrical activity increases growth cone calcium but fails to inhibit neurite outgrowth from rat sympathetic neurons. January 1, 1992. The Journal of neuroscience : the official journal of the Society for Neuroscience.

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  97. Regehr WG, Tank DW. The maintenance of LTP at hippocampal mossy fiber synapses is independent of sustained presynaptic calcium. September 1, 1991. Neuron.

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  98. Regehr WG, Tank DW. Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice. April 1, 1991. Journal of neuroscience methods.

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  99. Regehr WG, Tank DW. Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CA1 pyramidal cell dendrites. June 28, 1990. Nature.

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  100. Regehr WG, Pine J, Cohan CS, Mischke MD, Tank DW. Sealing cultured invertebrate neurons to embedded dish electrodes facilitates long-term stimulation and recording. November 1, 1989. Journal of neuroscience methods.

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  101. Regehr WG, Connor JA, Tank DW. Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation. October 12, 1989. Nature.

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  102. Regehr WG, Pine J, Rutledge DB. A long-term in vitro silicon-based microelectrode-neuron connection. December 1, 1988. IEEE transactions on bio-medical engineering.

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Harvard Medical School
Dept of Neurobiology
220 Longwood Ave
Boston MA 02115