Michael P. Kilgard

Sensory Experience and Cortical Plasticity

University of Texas at Dallas

Cortical plasticity depends upon:

• Sensory experience

• Behavioral relevance

The Cholinergic Basal Forebrain Provides a Diffuse Neuromodulatory Input to the Cortex

Nucleus Basalis

Exploring the Principles of Cortical Plasticity using:• Systematic Variation of Sensory Experience

• Nucleus Basalis Stimulation to

Gate Cortical Plasticity

Experienceor Instinct

Connectivity & Dynamics

Plasticity

Neural Representation

Importance

External world

• NB stimulation is paired with a sound several hundred times per day for ~20 days.

• Pairing occurs in awake unrestrained adult rats.

• Stimulation evokes no behavioral response.

• Stimulation efficacy is monitored with EEG.

Extracellular Recordings

Detailed Reconstruction of the Distributed Cortical Response

Best Frequency

Science, 1998

Tone Frequency - kHz

Nucleus Basalis Stimulation Generates Map Plasticity that is Specific to the Paired Tone

N = 20 rats; 1,060 A1 sites

Nature Neuroscience, 1998

Temporal Plasticity is Specific to the

Paired Repetition Rate

N = 15 rats, 720 sites

2 4 6 8 10 12 14 16 18 200

0.2

0.4

0.6

0.8

1

1.2

Repetition Rate (pulses/second)

Nor

mal

ized

Spi

ke R

ate

Control 15pps 9 kHz 15pps Seven Carriers

0 5 10 15 200

20

40

60

80

100

Best Repetition Rate(pulses/second)

Per

cent

of S

ites

A.

B.

Journal of Neurophysiology, 2001

Carrier frequency variability prevented map expansion and allowed temporal plasticity.

N = 13 rats, 687 sites

Stimulus Paired with NB Activation Determines

Degree and Direction of Receptive Field Plasticity

Frequency Bandwidth Plasticity N = 52 rats; 2,616 sites

Frequency Bandwidth is Shaped by Spatial and Temporal Stimulus Features

Modulation Rate (pps)0 5 10 15

Ton

e P

rob

abil

ity

15%

50 %

10

0%

Journal of Neurophysiology, 2001

Neuron 1

Inputs to Neuron A

Neuron 2

Receptive Field Overlap

Neuron A Neuron B

Inputs to Neuron B

Spike synchronization and RF overlap are correlated.

Brosch and Schreiner, 1999

After Map Expansion: ~85% shared inputs

After Sharper Frequency Tuning: ~25% shared inputs

What is the effect of cortical plasticity on spike synchonization?

Before plasticity: ~50% shared inputsBefore Plasticity: ~50% shared inputs

-50 -40 -30 -20 -10 0 10 20 30 40 500

200

400

600

800

1000

1200N

um

ber

of

Inte

rval

s

Interval (msec)

Cross-correlation: TC 025C1.MAT x TC025C2.MAT

Cross-correlationShift PredictorCorrelation strength

= correlation peak in normalized cross-correlation

histogram

Correlation width = width at half height

of correlation peak

Experience-Dependent Changes in Cortical Synchronization

• Map expansion sharpened synchronization– 15pps 9kHz tone trains

50% increase in cross-correlation height (p<0.0001)

17% decrease in cross-correlation width (p<0.01)

• Bandwidth narrowing smeared synchronization– Two different tone frequencies

50% decrease in cross-correlation height (p<0.0001)

22% increase in cross-correlation width (p<0.001)

• Intermediate stimuli caused no change in synchronization– 15pps tone trains with several different carrier frequencies

No change in cross-correlation height or width

N = 23 rats; 1,129 sites; 404 pairs

Experience-Dependent Changes in Cortical Synchronization (con’t)

• Broadband ripple stimulus sharpened synchronization– Sinusoidal power spectrum (one cycle / 6kHz )

54% increase in cross-correlation height (p<0.0001)

27% decrease in cross-correlation width (p<0.01)

N = 9 rats; 310 sites; 147 pairs

Pairing NB stimulation with aspectrotemporal sequence sharpens

response discharge coherence.

0 10 20 100 110 120 200 210 220 230

-10

0

10

20

30

0

10

20

30

0

10

20

30

40

0

10

20

30

40P

erce

nt o

f Site

s

Time (ms)

CF < 3.2 kHz

CF 3.2-7.75 kHz

CF 7.75-18.6 kHz

CF >18.6 kHz

Sharpened Cortical Response to High-Low-Noise Sequence

// //

// //

Naive After HLN Difference

5 10 15 20 25 300

10

20

30

40

Time to Peak Response (ms)

Per

cent

of S

ites

A)

B)

0 10 20 100 110 120 200 210 220 230-10

0

10

20

30

0

10

20

30

0

10

20

30

40

0

10

20

30

40P

erce

nt o

f Site

s

Time (ms)

CF < 3.2 kHz

CF 3.2-7.75 kHz

CF 7.75-18.6 kHz

CF >18.6 kHz

Sharpened Cortical Response to High-Low-Noise Sequence

// //

// //

Naive After HLN Difference

5 10 15 20 25 300

10

20

30

40

Time to Peak Response (ms)

Per

cent

of S

ites

A)

B)

Peak Latency: 15.2 vs. 18.2 ms (p< 0.00001)

Difference

NaiveAfter HLN

N = 13 rats, 450 sites

Time to Peak Response (ms)

Time (ms)

Spi

kes

per

Sec

ond

Sharpened Cortical Response to High-Low-Noise Sequence

0 10 20 100 110 120 200 210 220 230-10

0

10

20

30

0

10

20

30

0

10

20

30

40

0

10

20

30

40

Spi

kes

per

seco

nd

Time (ms)

CF < 3.2 kHz

CF 3.2-7.75 kHz

CF 7.75-18.6 kHz

CF >18.6 kHz

Sharpened Cortical Response to High-Low-Noise Sequence

// //

// //Naive After HLN Difference

5 10 15 20 25 300

20

40

60

Minimum Latency (ms)

Per

cent

of

Si te

s

5 10 15 20 25 300

20

40

60

Time to Peak Response (ms)

Per

cent

of

Si te

s

A) B)

C)

Increased Population Discharge Coherence

1.1 0.1 2.2+42%

1 0 1.2

1 0.6 1.7

1.5 0.1 0.8

0.3 0.7 2

0.2 1.7

1.3 1.6

Spikes per Element

Stretched

Compressed

Tones Reversed

Degraded

Degraded

Paired w/ BF

Sequence Reversed

High Tone Low Tone Noise Burst

0.1 0.7 2.5+67%

0.2 0.4 2.1

0.1 0.6 2.8+87%

1.3 0.4 0.3

0.5 0.1 2.7+80%

0.6 2.3+53%

0.2 1.5

Spikes per Element

Stretched

Compressed

Tones Reversed

Degraded

Degraded

Paired w/ BF

Sequence Reversed

0 100 200 300 400

1.2 1.4+195%

2.1+35%

1.1 0-100%

1.6

1 1.3+174%

2.6+67%

1.6 1+111%

1

0.4 0.9 2.4+54%

0.5 1.6

1.2 2.1+35%

Spikes per Element

Time (ms)

Stretched

Compressed

Tones Reversed

Degraded

Degraded

Paired w/ BF

Sequence Reversed

A)

B)

C)

Context-Dependent Facilitation

• 5% of sites in naïve animals respond with more spikes to the 5 kHz tone when preceded by the 12 kHz tone, compared to 25% after sequence pairing. (p< 0.005)

• 35% of sites in naïve animals respond with more spikes to the noise when preceded by the high and low tones, compared to 58% after sequence pairing. (p< 0.01)

• 13% of sites in naïve animals respond with more spikes to the 12 kHz tone when preceded by the 5 kHz tone, compared to 10% after sequence pairing.

Context-Dependent Facilitation - Group Data

N = 13 rats, 261 sites

Sensory Experience Controls:

• Cortical Topography

• Receptive Field Size

• Maximum Following Rate

• Spectrotemporal Selectivity

• Synchronization

• 55% increase in response strength– 1.4 vs. 0.9 spikes per noise burst (p< 0.0001)

• 22% decrease in frequency bandwidth– 1.8 vs. 2.2 octaves at 30dB above threshold (p< 0.0001)

• One millisecond decrease in minimum latency– 15.8 vs. 16.8 ms (p< 0.005)

• Two decibel decrease in threshold– 17 vs. 19 dB ms (p< 0.01)

• Increased synchronization– 13% increase in cross-correlation height (p< 0.01)

Enrichment Effects

N = 14 rats, 738 sites

Experienceor Instinct

Connectivity & Dynamics

Plasticity

Neural Representation

Importance

External world

Rules of Cortical Plasticity

Experienceor Instinct

Connectivity & Dynamics

Plasticity

Neural Representation

Importance

External world

Experienceor Instinct

Connectivity & Dynamics

Plasticity

Behavioral Change

Neural Representation

Importance

External world

Map BW LatencyEnd of

ResponseSpontaneous

ActivityTone

ResponseRipple

Response

One Frequency 0 0 0 0

Two Frequencies 0 0 0

MultipleFrequencies

0 0 0

Spectral Ripple 0

Spectral Stimuli

Map BW LatencyEnd of

ResponseSpontaneous

ActivityTone

Response

MaximumFollowing

Rate

CombinationSensitivity

15 pps Tone Trains - 9kHz Carrier 0 0 0 0

15 pps Tone Trains - Multiple Carrier Frequencies

0 0 0 0 0

5 pps Tone Trains - Multiple Carrier Frequencies

0 0 0

High-Low-NoiseSequence

0 0

Temporal Stimuli

Rules of Cortical PlasticityMap BW Latency

End ofResponse

SpontaneousActivity

ToneResponse

MaximumFollowing

Rate

CombinationSensitivity

One Frequency 0 0 0 0

Two Frequencies 0 0 0

MultipleFrequencies

0 0

Spectral Ripple

15 pps Tone Trains - 9kHz Carrier

0 0 0 0

15 pps Tone Trains - Multiple Carrier Frequencies

0 0 0 0 0

5 pps Tone Trains - Multiple Carrier Frequencies

0 0 0

High-Low-NoiseSequence

0 0

Behavioral Relevance

Neural Activity

- Internal Representation

External World-Sensory Input

Neural Plasticity- Learning and

Memory

Plasticity Rules- Educated Guess

RF Increase Increased Synchrony

Temporal Task: BF Pairing 15 pps, 9 kHz Tone

Width

RF Decrease Decreased Synchrony

Spectral Task: BF Pairing 2 Frequencies Randomly Interleaved

Width

RF Increase No Change in Synchrony

Temporal and Spectral Task: BF Pairing 15 pps Multiple Frequencies

Width

No Change in RF Increased Synchrony

Spectral-temporal Task: BF Pairing Moving Stimuli (FM’s)

Width

RF Decrease Increased Synchrony

Complex Spectral Task: BF Pairing Steady State High Density Ripple

Width