Centre for Synaptic Plasticity Glutamate receptor and Synaptic

Centre for Synaptic Plasticity Glutamate receptor and Synaptic Plasticity Beyond our genetic destiny: we are our life’s experiences • The human brain, a 3 pound mass of interwoven nerve cells determines our sensations, emotions, memory, intelligence, creativity, thought Centre for Synaptic Plasticity and action. It is the

Long term potentiation: the synaptic basis of memory Tim Bliss Centre for Synaptic Plasticity

Glutamate is the major excitatory neurotransmitter in the CNS and acts on four main sub-classes of receptor Jeff Watkins NMDA AMPA Kainate Centre for Synaptic Plasticity m. Glu

Bi-directional synaptic plasticity: LTP and LTD long-term potentiation ( Induction Transduction Expression long-term depression ( Centre for Synaptic Plasticity ) )

AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature 361, 31 -39 Centre for Synaptic Plasticity

Centre for Synaptic Plasticity

Centre for Synaptic Plasticity

Two forms of LTD in the perirhinal cortex NMDAR-LTD m. Glu. R-LTD NMDAR AMPAR Centre for Synaptic Plasticity m. Glu. R AMPAR

Jihoon Jo Centre for Synaptic Plasticity Kei Cho Heon Seok

Inhibition of the PICK 1 -Glu. A 2 interaction blocks m. Glu. R-LTD but not NMDAR-LTD N m. Glu. R-LTD C PICK 1 GRIP 1 2 1+2 3 4 3+4 100 ms 1 3 100 p. A 1 2 1+2 3 4 3+4 D-AP 5 1 2 2 3 4 4 Pep 2 -EVKI 1 Hz Centre for Synaptic Plasticity Pep 2 -EVKI Pep 2 -SVKE Jo et al, (2008) Neuron. 60, 1095 -1111 100 ms 100 p. A NSF AP 2 5 Hz Pep 2 -EVKI Pep 2 -SVKE

b-gal + NCS-1 -RNAi. Luciferase-RNAi NCS-1 RNAi blocks m. Glu. R-LTD but not NMDAR-LTD Β-gal b-gal NCS-1 Merged Luciferase RNAi NCS-1 RNAi NMDAR-LTD 1 3 2 4 1+2 3+4 1 2 1+2 3 4 3+4 100 ms 1 D-AP 5 100 ms 2 1 2 3 3 4 4 NCS-1 RNAi 1 Hz Centre for Synaptic Plasticity Control cells Jo et al, (2008) Neuron. 60, 1095 -1111 NCS-1 RNAi 5 Hz Luciferase RNAi 100 p. A m. Glu. R-LTD

Interactions between PICK 1 and NCS-1 Ca sensitivity of NCS-1 and PICK 1 interactions NCS-1 binds the BAR domain of PICK 1 NCS-1 Jo et al, (2008) Neuron. 60, 1095 -1111 4 35 12 1 - IC K 1 -P ST G S G IC K 1 IC 1 - 41 fu P T- 13 6 ll K 1 G PICK 1 5 BAR PDZ NCS-1 Centre for Synaptic Plasticity 416 GST-PICK 1 1000 -P IC 100 35 4 - 50 ST 10 G [Ca 2+]free (m. M) 1 354 135 121

The GST-BAR fusion protein blocks m. Glu. R-LTD but not NMDAR-LTD 1 2 1+2 3 4 3+4 100 ms 1 1 2 1+2 3 4 3+4 D-AP 5 100 ms 1 2 100 p. A m. Glu. R-LTD 2 3 3 4 4 GST-BAR GST 1 Hz Centre for Synaptic Plasticity Jo et al, (2008) Neuron. 60, 1095 -1111 GST-BAR 5 Hz GST-BAR GST

m. Glu. R- LTD in the perirhinal cortex Jo et al, (2008) Neuron. 60, 1095 -1111 Centre for Synaptic Plasticity

AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature 361, 31 -39 Centre for Synaptic Plasticity

Simultaneous whole-cell recording and Ca 2+ imaging form neurons in slices PMT Alford, Frenguelli et al, (1993) J. Physiol. 469, 693 -716 Centre for Synaptic Plasticity

Simultaneous whole-cell recording and Ca 2+ imaging form neurons in slices PMT Centre for Synaptic Plasticity Alford, Frenguelli et al, (1993) J. Physiol. 469, 693 -716

… Reveals NMDAR-induced transient Ca 2+ signals in dendritic spines Synaptic current Calcium transient 100 Hz, 1 s 2 Alford, Frenguelli et al, (1993) J. Physiol. 469, 693 -716 Centre for Synaptic Plasticity

Hippocalcin RNAi and GFP-transfected hippocampal neurons LTP LTD Centre for Synaptic Plasticity Mascia Amici & Sheila Dargan, unpublished

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

AMPARs mediate low frequency excitatory synaptic transmission Bliss & Collingridge (1993) Nature 361, 31 -39 Centre for Synaptic Plasticity