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Beyond our genetic destiny: we are our life’s experiences

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Beyond our genetic destiny: we are our life’s experiences

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  1. The human brain, a 3-pound mass of interwoven nerve cells determines our sensations, emotions, memory, intelligence, creativity, thought and action. It is the part of our anatomy that truly makes us who we are. It is more complex and versatile than any computer. Understanding how the brain works is one of the greatest challenges for science in the 21st century. Centre for Synaptic Plasticity Glutamate receptor and Synaptic Plasticity Beyond our genetic destiny: we are our life’s experiences

  2. Long term potentiation: the synaptic basis of memory Tim Bliss

  3. Glutamate is the major excitatory neurotransmitter in the CNS and acts on four main sub-classes of receptor NMDA AMPA Kainate mGlu Jeff Watkins AMPA Kainate

  4. Bi-directional synaptic plasticity: LTP and LTD long-term potentiation ( ) Transduction Induction Expression long-term depression ( )

  5. AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature361, 31-39

  6. Two forms of LTD in the perirhinal cortex NMDAR-LTD mGluR-LTD NMDAR mGluR AMPAR AMPAR

  7. Kei Cho Jihoon Jo Heon Seok

  8.    N 1 2 1+2 C 3+4 3 4 PICK1 GRIP NSF AP2 100 ms 100 pA 1 3 2 4 Pep2-EVKI 1 Hz Pep2-SVKE Inhibition of the PICK1-GluA2 interaction blocks mGluR-LTD but not NMDAR-LTD NMDAR-LTD mGluR-LTD 1 2 1+2 3 3+4 4 100 ms D-AP5 100 pA 1 2 3 4 Pep2-EVKI Pep2-SVKE Pep2-EVKI Pep2-EVKI Pep2-SVKE 5 Hz Pep2-SVKE Jo et al, (2008) Neuron. 60, 1095-1111

  9. b-gal NCS-1 Merged b-gal + Luciferase-RNAi 1 1 2 1+2 2 1+2  3 4 3+4 3 4 3+4 D-AP5 100 ms 100 ms 100 pA b-gal + NCS-1-RNAi 100 pA 2 1 1 2 3 3 4 4 NCS-1 RNAi NCS-1 RNAi  Luciferase RNAi Control cells 5 Hz 1 Hz   NCS-1 RNAi blocks mGluR-LTD but not NMDAR-LTD Β-gal NCS-1 Merged Luciferase RNAi NCS-1 RNAi NMDAR-LTD mGluR-LTD Jo et al, (2008) Neuron. 60, 1095-1111

  10. GST-PICK1354-416 GST-PICK1 1-135 GST-PICK1full GST-PICK1121-354 354 135 416 121 GST-PICK1 BAR PDZ 50 1 10 100 1000 [Ca2+]free (mM) NCS-1 PICK1 Interactions between PICK1 and NCS-1 Ca sensitivity of NCS-1 and PICK1 interactions NCS-1 binds the BAR domain of PICK1 NCS-1 Jo et al, (2008) Neuron. 60, 1095-1111

  11.    The GST-BAR fusion protein blocks mGluR-LTD but not NMDAR-LTD NMDAR-LTD mGluR-LTD 2 1+2 1 1 2 1+2 3 3+4 4 3 3+4 4 100 ms 100 ms D-AP5 100 pA 1 100 pA 1 2 2 3 3 4 4 GST-BAR GST GST-BAR GST-BAR GST GST-BAR GST 5 Hz GST 1 Hz Jo et al, (2008) Neuron. 60, 1095-1111

  12. mGluR- LTD in the perirhinal cortex Jo et al, (2008) Neuron. 60, 1095-1111

  13. AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature361, 31-39

  14. PMT Simultaneous whole-cell recording and Ca2+ imaging form neurons in slices Alford, Frenguelli et al, (1993) J. Physiol. 469, 693-716

  15. PMT Simultaneous whole-cell recording and Ca2+ imaging form neurons in slices Alford, Frenguelli et al, (1993) J. Physiol. 469, 693-716

  16. Synaptic current Calcium transient 100 Hz, 1 s2 … Reveals NMDAR-induced transient Ca2+ signals in dendritic spines Alford, Frenguelli et al, (1993) J. Physiol. 469, 693-716

  17. Hippocalcin RNAi and GFP-transfected hippocampal neurons LTP LTD Mascia Amici & Sheila Dargan, unpublished

  18. Activation of NMDARs results in internalisation of AMPARs Ashby et a.l (2004) J. Neurosci.24; 5172 - 5176

  19. AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature361, 31-39

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