Spike Timing-Dependent Synaptic Plasticity in Neuronal Networks

1. Spike timing-dependent plasticity Guoqiang Bi Department of Neurobiology University of Pittsburgh School of Medicine

2. Cajal, 1894 Temporally varying patterns of input Spatially distributed patterns of storage ???

3. When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased. — Donald O. Hebb, 1949

4. “Cells that fire together, wire together” Question: How precise do the cells need to fire together in order to wire together?

5. Spike-timing-dependent synaptic plasticity • How does the timing of pre- and postsynaptic activity affect synaptic modification? • STDP in neuronal networks • How may a network change its configuration according to the temporal structure of in input stimuli? • Temporal integration of STDP • How is a synapse modified by natural spike trains?

8. Synaptic connectivity between cultured neurons A. Glu - Glu B. Glu - GABA S1 S2 S1 S2 R1 R1 * R2 R2 + bicuculline + CNQX + bicuculline & CNQX + CNQX & bicuculline

9. Paired pre- and postsynaptic spiking – a “true Hebbian” paradigm

10. LTP induced by paired spiking with positive timing A B C

11. LTD induced by paired spiking with negative timing A B C

12. Markram et al. 1997

13. A critical window for synaptic modification induced by correlated spiking Bi & Poo 1998

14. Froemke & Dan 2002

15. Zhang et al. 1998

16. Feldman 2000

17. Nishiyama et al. 2000

18. Bell et al. 1997

19. Spike-timing-dependent synaptic plasticity • Paired pre- and postsynaptic spiking induces LTP and LTD, depending on the precise spike timing • STDP is sensitive to neuronal cell type • STDP requires NMDA receptors • STDP in neuronal networks • How may a network change its configuration according to the temporal structure of in input stimuli? • Temporal integration of STDP • How is a synapse modified by natural spike trains? • Spike-timing-dependent synaptic plasticity • Paired pre- and postsynaptic spiking induces LTP and LTD, depending on the precise spike timing • STDP is sensitive to neuronal cell type • STDP requires NMDA receptors • STDP in neuronal networks • How may a network change its configuration according to the temporal structure of in input stimuli? • Temporal integration of STDP • How is a synapse modified by natural spike trains?

20. Correlated spiking at remote synapses through convergent polysynaptic pathways – a “delay-line” mechanism

21. 1 2 A 3 EPSC 700 pA B 3 2 1 150 pA S Polysynaptic pathways in small neural networks

22. IPI(ms): 60 40 4 3 2 1 S Long-term pathway remodeling induced by repetitive paired-pulse stimulation

23. Sensitivity of pathway remodeling to inter- pulse interval (IPI) of input stimuli IPI(ms): 100 50 20 3 2 1 S

24. Dependence of pathway remodeling on inter- pulse interval (IPI) of input stimuli IPI(ms): 150 65 65 55 4 3 2 1 S

25. Pathway remodeling induced by paired-pulse stimuli of different IPIs

26. IPI1  IPI2 IPI1  IPI2

27. LTP and LTD at remote synapses induced by local paired pulse stimulation A1 A2 B1 B2

28. Spike-timing-dependent synaptic plasticity • Paired pre- and postsynaptic spiking induces LTP and LTD, depending on the precise spike timing • STDP is sensitive to neuronal cell type • STDP requires NMDA receptors • Remote STDP in neuronal networks • STDP occurs at synaptic sites remote to network input nodes • Spike timing within the network can be coordinated by delay-lines formed by polysynaptic pathways. • Temporal integration of STDP • Spike-timing-dependent synaptic plasticity • Paired pre- and postsynaptic spiking induces LTP and LTD, depending on the precise spike timing • STDP is sensitive to neuronal cell type • STDP requires NMDA receptors • Remote STDP in neuronal networks • STDP occurs at synaptic sites remote to network input nodes • Spike timing within the network can be coordinated by delay-lines formed by polysynaptic pathways. • Temporal integration of STDP

29. Temporal integration of STDP – theoretical considerations “Pan-spike” interaction “Near-neighbor” interaction

30. Temporal integration of STDP – Triplet interactions

31. LTP induced by a special case of “triplet” spiking A B Bi & Poo 1998

32. Temporally asymmetric interaction between LTP- and LTD-inducing processes

33. Froemke & Dan 2002

34. Spike-timing-dependent synaptic plasticity • Paired pre- and postsynaptic spiking induces LTP and LTD, depending on the precise spike timing • STDP is sensitive to neuronal cell type • STDP requires NMDA receptors • Remote STDP in neuronal networks • STDP occurs at synaptic sites remote to network input nodes • Spike timing within the network can be coordinated by delay-lines formed by polysynaptic pathways. • Temporal integration of STDP • In hippocampal cultures, LTP- and LTD-inducing processes integrate asymmetrically • Different systems with the same spike-timing window may have different integration rules.

35. Acknowledgements UC San DiegoMu-ming Poo (Berkeley) Benedikt Berninger (Munich) University of Pittsburgh Pakming Lau Huaixing Wang Joyeeta Dutta David Nauen