35
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

Embed Size (px)

Citation preview

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

???

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?

+ bicuculline

+ CNQX & bicuculline

A. Glu - Glu

+ CNQX

+ bicuculline & CNQX

B. Glu - GABA

S1 S2

R2

R1*

S1 S2

R2

R1

Synaptic connectivity between cultured neurons

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

0 10 20 30 40 500.2

0.4

0.6

0.8

1.0

EP

SC

am

plit

ude (

nA

)

-20 -10 0 10 20 30

0.6

0.8

1.0

1.2

1.4

1.6

1.8 AP-5

Norm

aliz

ed E

PS

C

Time (min)

0 10 20 30 40 500

50

100

150

200E

PS

C a

mplit

ude (

pA

)

A

B

C

LTP induced by paired spiking with positive timing

0 10 20 30 40 500.1

0.2

0.3

0.4

0.5

EP

SC

am

plit

ude (

nA

)

-20 -10 0 10 20 300.4

0.6

0.8

1.0

1.2

1.4 AP-5

Norm

aliz

ed E

PS

C

Time (min)

0 10 20 30 40 500.0

0.1

0.2

0.3

0.4

0.5E

PS

C a

mplit

ude (

nA

)

A

B

C

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

IPI'

(i) (ii)

positively spike timing negative spike timing

IPI

t

IPI

t

IPI'

0 20 40 60 80

A1 2

3

Polysynaptic pathways in small neural networks

B

0 10 20 30 40 50 60

10

20

30

40

50

60

Time (min)

Tim

e (

ms)

1

3

2

S150 pA

EPSC700 pA

0 20 40 60 80 1000

20

40

60

80

Time (min)

Tim

e (

ms)

321S

4

IPI(ms): 60 40

Long-term pathway remodeling inducedby repetitive paired-pulse stimulation

0 20 40 60 80 100 1200

10

20

30

40

Time (min)

Tim

e (m

s)

IPI(ms): 100 5020

3

2

1

S

Sensitivity of pathway remodeling to inter-pulse interval (IPI) of input stimuli

0 20 40 60 80 100

0

20

40

60

80

100

120

Time (min)

Tim

e (m

s)

IPI(ms): 150 65 65 55

321

S

4

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

50 100 150 200-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0NormalAPV

P

Inter-pulse interval (ms)

Pathway remodeling induced bypaired-pulse stimuli of different IPIs

IPI1 IPI2IPI1 IPI2

0.0

0.1

0.2

0.3

**

**

APV15

0-20

0ms

100-

150m

s

50-1

00m

s

10-5

0ms

Abs

(P

)

-0.5 0.0 0.5

-0.5

0.0

0.5

P2

P1

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

A1 A2

B1 B2

0 10 20 30 40 500

50

100

Time (min)

EP

SC

am

plitu

de (

pA)

0 10 20 30 40 50 600

50

100

150

EP

SC

am

plitu

de (

pA)

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

-20 -10 0 10 20 30

0.6

0.8

1.0

1.2

1.4

1.6

Norm

aliz

ed E

PS

C

Time (min)

0 10 20 30 40 500.0

0.2

0.4

0.6

EP

SC

am

plit

ute

(nA

)A

B

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