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Temporally varying patterns of input

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

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

“Cells that fire together, wire together” 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.

Question:

How precise do the cells need to fire together in

order to wire together?

- Spike-timing-dependent synaptic plasticity 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.
- 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?

Synaptic connectivity between cultured neurons 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.

A. Glu - Glu

B. Glu - GABA

S1 S2

S1 S2

R1

R1

*

R2

R2

+ bicuculline

+ CNQX

+ bicuculline & CNQX

+ CNQX & bicuculline

Paired pre- and postsynaptic spiking 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.

– a “true Hebbian” paradigm

LTP induced by paired spiking with positive timing 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.

A

B

C

LTD induced by paired spiking with negative timing 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.

A

B

C

Markram et al. 1997 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.

A critical window for synaptic modification 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.

induced by correlated spiking

Bi & Poo 1998

Froemke & Dan 2002 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.

Zhang et al. 1998 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.

Feldman 2000 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.

Nishiyama et al. 2000 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.

Bell et al. 1997 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.

- Spike-timing-dependent synaptic plasticity 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.
- 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?

Correlated spiking at remote synapses through convergent 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.

polysynaptic pathways – a “delay-line” mechanism

1 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.

2

A

3

EPSC

700 pA

B

3

2

1

150 pA

S

Polysynaptic pathways in small neural networks

IPI(ms): 60 40 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.

4

3

2

1

S

Long-term pathway remodeling induced

by repetitive paired-pulse stimulation

Sensitivity of pathway remodeling to inter- 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.

pulse interval (IPI) of input stimuli

IPI(ms): 100 50 20

3

2

1

S

Dependence of pathway remodeling on inter- 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.

pulse interval (IPI) of input stimuli

IPI(ms): 150 65 65 55

4

3

2

1

S

Pathway remodeling induced by 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.

paired-pulse stimuli of different IPIs

IPI1 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. IPI2

IPI1 IPI2

LTP and LTD at remote synapses 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.

induced by local paired pulse stimulation

A1

A2

B1

B2

- Spike-timing-dependent synaptic plasticity 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.
- 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

Temporal integration of STDP – theoretical considerations 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.

“Pan-spike” interaction

“Near-neighbor” interaction

Temporal integration of STDP – Triplet interactions 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.

LTP induced by a special case 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.

of “triplet” spiking

A

B

Bi & Poo 1998

Temporally asymmetric interaction between 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.

LTP- and LTD-inducing processes

Froemke & Dan 2002 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.

- Spike-timing-dependent synaptic plasticity 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.
- 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.

Acknowledgements 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.

UC San DiegoMu-ming Poo (Berkeley)

Benedikt Berninger (Munich)

University of Pittsburgh Pakming Lau

Huaixing Wang

Joyeeta Dutta

David Nauen

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