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

Spike timing-dependent plasticity

Guoqiang Bi

Department of Neurobiology University of Pittsburgh School of Medicine

Temporally varying patterns of input

Spatially distributed patterns of storage

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Cajal, 1894

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”

Question:

How precise do the cells need to fire together in order to wire together?

1. Spike-timing-dependent synaptic plasticity

• How does the timing of pre- and postsynaptic activity affect synaptic modification?

2. STDP in neuronal networks

• How may a network change its configuration according to the temporal structure of in input stimuli?

3. Temporal integration of STDP

• How is a synapse modified by natural spike trains?

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+ CNQX & bicuculline

A. Glu - Glu

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B. Glu - GABA

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Synaptic connectivity between cultured neurons

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

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LTP induced by paired spiking with positive timing

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LTD induced by paired spiking with negative timing

Markram et al. 1997

A critical window for synaptic modificationinduced by correlated spiking

Bi & Poo 1998

Froemke & Dan 2002

Zhang et al. 1998

Feldman 2000

Nishiyama et al. 2000

Bell et al. 1997

1. 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

2. STDP in neuronal networks• How may a network change its configuration according to the

temporal structure of in input stimuli?

3. Temporal integration of STDP• How is a synapse modified by natural spike trains?

1. 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

2. STDP in neuronal networks• How may a network change its configuration according to the

temporal structure of in input stimuli?

3. Temporal integration of STDP• How is a synapse modified by natural spike trains?

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

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positively spike timing negative spike timing

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Long-term pathway remodeling inducedby repetitive paired-pulse stimulation

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Dependence of pathway remodeling on inter-pulse interval (IPI) of input stimuli

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Pathway remodeling induced bypaired-pulse stimuli of different IPIs

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LTP and LTD at remote synapses induced by local paired pulse stimulation

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1. 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

2. 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.

3. Temporal integration of STDP

1. 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

2. 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.

3. Temporal integration of STDP

Temporal integration of STDP – theoretical considerations

“Pan-spike” interaction

“Near-neighbor” interaction

Temporal integration of STDP – Triplet interactions

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LTP induced by a special case of “triplet” spiking

Bi & Poo 1998

Temporally asymmetric interaction between LTP- and LTD-inducing processes

Froemke & Dan 2002

1. 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

2. 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.

3. 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

UC San Diego Mu-ming Poo (Berkeley)

Benedikt Berninger (Munich)

University of Pittsburgh Pakming Lau

Huaixing Wang

Joyeeta Dutta

David Nauen