OPC Maturation Article Presentation


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Presentation for the Nature paper: Bergles, et al. Glutamatergic synapses on
oligodendrocyte precursor
cells in the hippocampus, request download for animations

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OPC Maturation Article Presentation

  1. 1. <ul><li>Glutamatergic synapses on </li></ul><ul><li>oligodendrocyte precursor </li></ul><ul><li>cells in the hippocampus </li></ul><ul><li>Dwight E. Bergles*, J. David B. Roberts², Peter Somogyi²& Craig E. Jahr* </li></ul><ul><li>* Vollum Institute, L474, Oregon Health Sciences University, Portland, </li></ul><ul><li>Oregon 97201, USA </li></ul><ul><li>²MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, </li></ul><ul><li>University of Oxford, Oxford OX1 3TH, UK </li></ul><ul><li>NATURE |VOL 405 | 11 MAY 2000 |www.nature.com </li></ul>HHMI-IMBS Presentation: Richard Myers
  2. 2. In vitro OPC maturation is blocked by glutamate Ca2+ ion AMPA Receptor Ca2+ Channel Glutamate Molecule Ca2+ ion X Glutamate Molecule OPC Mature Oligodendrocyte Inward Current X
  3. 3. Currents in NG2+ OPCs Figure 1 Synaptic responses from identi®ed OPCs in hippocampal slices. a, Currentclamp recording of membrane responses to current injection (-80 to 140 pA; step size, 20 pA). b, Evoked responses to Schaffer collateral/commissural ®bre stimulation, recorded in voltage-clamp (holding potential, -90 mV; lower trace) and current-clamp (membrane potential = -90 mV; upper trace). Traces are averages of 15 consecutive responses recorded from the same cell. Stimulus: 30mA, 100ms. c, Reconstruction of a biocytin-®lled OPC. d, Micrograph of the same OPC as in d, visualized by AMCAconjugated streptavidin. e, NG2-immunoreactivity of same region of the slice as shown in d. Scale bars for c and d, 20mm; d and e are at the same magni®cation.
  4. 4. Neuron to OPC signal in rat brain <ul><li>CA3 neurons were stimulated with Glutamate </li></ul><ul><li>Signal was relayed to CA1 neurons and then OPCs </li></ul><ul><li>OPC membrane current was measured </li></ul><ul><li>Currents abolished by TTX (Na+ channel blocker) </li></ul>OPC
  5. 5. AMPA receptors on OPCs receive glutamate signals AMPA Receptor Ca2+ Channel Ca2+ ion Glutamate Molecule Ca2+ ion X OPC Inward Current Blocked X NBQX (AMPA Receptor Inhibitor) X
  6. 6. Glutamate induced currents in OPCs requires Ca2+ influx Cd2+ ion AMPA Receptor Ca2+ Channel Ca2+ ion Glutamate Molecule Ca2+ ion X OPC Inward Current Blocked X Glutamate Molecule Cd2+ ion
  7. 7. EM of Neuron-OPC synaptic interation <ul><li>b : Axon bouton forming a synpase </li></ul><ul><li>s : dendritic spine from neighboring neuron </li></ul><ul><li>black: biocytin labeled OPC </li></ul><ul><li>Notice the glutamate vesicles forming at the bouton membrane </li></ul>
  8. 8. EM of Neuron-OPC synaptic interation <ul><li>OPC labeled with NG2 silver stain </li></ul><ul><li>f : OPC targeted by vesicle signaling as opposed to neighboring neuron </li></ul><ul><li>OPC membrane is thinner than neighboring neurons </li></ul>
  9. 9. Neurons control self-myelination through regulation of OPC maturation Mature Oligodendrocyte OPCs do not mature OPC Maturation Demyelination Remyelination X