Anesthetized Microelectrode Mapping

Michael P. Kilgard

Sensory Experience and Cortical Plasticity

University of Texas at Dallas

20±10 vs. 75±20 μV 81±19 vs. 37±20 μV

0 50 100 150 200 250

Week 1

Am

plit

ud

e (

mV

)

Time (ms)0 50 100 150 200 250

Week 2

Time (ms)0 50 100 150 200 250

Week 5

Time (ms)

0 50 100 150 200 250

Week 12

Time (ms)

.10

.05

0

-.05

-.10

Red Group Enriched Blue Enriched

Environmental Enrichment

22 rats total

• 40% increase in response strength– 1.4 vs. 1.0 spikes per noise burst (p< 0.0001)

• 10% decrease in frequency bandwidth– 2.0 vs. 2.2 octaves at 40dB above threshold (p< 0.05)

• Three decibel decrease in threshold– 17 vs. 20 dB ms (p< 0.001)

1 2 4 8 16 320

20

40

60

80

Frequency (kHz)

Inte

nsity

(dB

SP

L)

A.

1 2 4 8 16 320

20

40

60

80

Frequency (kHz)

Inte

nsity

(dB

SP

L)

B.

0 10 20 30 400

50

100C.

Time (ms)

Spi

kes/

s

1 2 4 8 16 320

20

40

60

80

Frequency (kHz)

Inte

nsity

(dB

SP

L)

A.

1 2 4 8 16 320

20

40

60

80

Frequency (kHz)

Inte

nsity

(dB

SP

L)

B.

0 10 20 30 400

50

100C.

Time (ms)

Spi

kes/

s

Enriched

Standard

A1 Enrichment Effects - after 2 months

N = 16 rats, 820 sites

Stronger, More Selective, and More Sensitive

Environmental Enrichment Improves Response Strength, Threshold, Selectivity, and Latency of Auditory Cortex Neurons Engineer ND, Percaccio CR, Pandya PK, Moucha R, Rathbun DL, Kilgard MP. Journal of Neurophysiology, 2004.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15014105

High

Low

Cochlea Cortex

High

Low

Cochlea Cortex

Cortical Map Plasticity

High-density microelectrode mapping technique

Best Frequency

Nucleus Basalis Activity Enables Cortical Map ReorganizationM.P. Kilgard, M.M. Merzenich, Science 279(5357): 1714-1718, 1998. download file

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9497289&dopt=Abstract

http://www.utdallas.edu/~kilgard/kilgardscience.pdf

http://www.utdallas.edu/~kilgard/kilgardscience.pdf

Tone Frequency - kHz

Nucleus Basalis Stimulation Generates Frequency-Specific

Map Plasticity

N = 20 rats; 1,060 A1 sites

Differences between A1 and Posterior Auditory Field – submitted

2 4 8 16 32

10

30

50

70

Controls - Percent of PAF Responding

Inte

nsi

ty (

dB

)

A

0

20

40

60

80

100

2 4 8 16 32

10

30

50

70

19kHz paired - Percent of PAF Responding

Inte

nsi

ty (

dB

)

B

-20

-10

0

10

20

2 4 8 16 32

10

30

50

70

Difference in PAF Percent after 19 kHz Paired

Inte

nsi

ty (

dB

)

Tone Frequency (kHz)

C

• High frequency map expansion , p<0.01

• Decreased bandwidth (30 dB above threshold)

– 3.0 vs. 3.6 octaves, p<0.001

• Shorter time to peak– 56 vs. 73 ms, p<.01

Plasticity in Posterior Auditory Field

N = 12 rats; 396 PAF sites

Manuscript in preparation

Temporal Processing

Typical Response of A1 Neurons to Tone Trains

• After Pairing NB Stimulation with 15 Hz Tone Trains

• After Pairing NB Stimulation with 5 Hz Tone Trains


Plasticity of Temporal Information Processing

in the Primary Auditory Cortex M.P. Kilgard, M.M. Merzenich

Nature Neuroscience1(8): 727-731, 1998

download file

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%

Spatial Variability

Leads toSmaller RF’s

Temporal Modulation

Leads toLarger RF’s

Sensory Input Directs Spatial and Temporal Plasticity in Primary Auditory CortexM.P. Kilgard, P.K. Pandya, J.L. Vazquez, Gehi, A., C.E. Schreiner, M.M. Merzenich

Journal of Neurophysiology, 86: 339-353, 2001. download file

How do neural networks learn to represent complex sounds?

• Spectrotemporal Sequences

100ms 20ms

High Tone(12 kHz)

Low Tone(5 kHz)

Noise Burst

Paired w/ NB stimulation

100ms 20ms

High Tone(12 kHz)

Low Tone(5 kHz)

Noise Burst

Unpaired background

sounds}

Context-Dependent Facilitation

100ms 20ms

High Tone(12 kHz)

Low Tone(5 kHz)

Noise Burst

Num

ber

of S

pike

s0 100 200 300 400ms

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

Context-Dependent Facilitation - Group Data

100ms 20ms

Low Tone(5 kHz)

Noise Burst

Noise Burst

High Tone(12 kHz)


Order Sensitive Plasticity in Adult Primary Auditory CortexM.P. Kilgard, M.M. Merzenich

Proceedings of the National Academy of Sciences 99: 3205-3209, 2002. download file

SchematicIllustration

• 25% of sites respond with more spikes to the low tone when preceded by the high tone, compared to 5% of sites in naïve animals. (p< 0.005)


Low Tone(5 kHz)

100ms 20ms

High Tone(12 kHz)

Low Tone(5 kHz)

Noise Burst





• 10% of sites respond with more spikes to the high tone when preceded by the low tone, compared to 13% of sites in naïve animals.


100ms 20ms

Noise Burst

High Tone(12 kHz)

High Tone(12 kHz)


Low Tone(5 kHz)




Target stimulus (CS+)

Add first distractor

(CS-1)

Add second distractor

(CS-2)

Add third distractor

(CS-3)

Task

A) Sequence detection

B) Frequency discrimination

C) Triplet distractor- High first

D) Sequence element discrimination

E) Triplet distractor- Noise first

F) Reverse Order

Fre

quen

cy (

kHz)

Time (ms)

H L N

H L N

L L L H H H

H H H

H H H

L L L

L L L

N N N

N N N

NL

N L H

H

H L N

H L N

H L N

None

None

None None

None

None None

Map Auditory Cortex

Time (months)

Operant Training

Discrimination Performance

Differential Plasticity Effects

How do cortical neurons learn to represent speech sounds?

‘SASH’ Group - Spectrotemporal discharge patterns of A1 neurons to ‘sash’ vocalization (n= 5 rats)

kHz

16kHz @50dB:

35 % 1.9

55 % 5.3

(p<0.0005)

Sensory Experience Controls:

• Response Strength

• Cortical Topography

• Receptive Field Size

• Maximum Following Rate

• Synchronization

• Spectrotemporal Selectivity

050

100150

Spi

ke

Rat

e (H

z)

050

100150

Spi

ke

Rat

e (H

z)

050

100150

Spi

ke

Rat

e (H

z)F

requ

ency

(kH

z)

5 102025

Fre

quen

cy (

kHz)

5 102025

Fre

quen

cy (

kHz)

5 102025

050

100150

050

100150

050

100150

5 102025

5 102025

5 102025

A) 'back' E) 'back' - modified

B) 'pack' F) 'pack' - modified

C) 'sash' G) 'sash' - modified

50 100 150 200 250 300 350

50

100

150

Time (ms)

Spi

ke

Rat

e (H

z)

pack

backa sh

D) Neural responses to normal speech

50 100 150 200 250 300 350

50

100

150

Time (ms)

ba

p as a

ck

cksh

H) Neural responses to modified speech

Activity from a single A1 neuron recorded in an awake rat

in response to normal and enhanced human speech sounds

Behavioral Relevance

Neural Activity

- Internal Representation

External World-Sensory Input

Neural Plasticity- Learning and

Memory

Plasticity Rules- Educated Guess

BehavioralChange

Training Experiments - Navzer Engineer

Amanda Puckett

Crystal Novitski

Enrichment Experiments - Navzer Engineer

Cherie Percaccio

Receptive Field Plasticity - Pritesh Pandya

Synchrony Experiments - Jessica Vazquez

FM Experiments - Raluca Moucha

Speech Experiments - Pritesh Pandya

and

Acknowledgements:

and

http://www.canfoundation.org/aboutcan/aboutcan.cfm

http://www.nidcd.nih.gov/

Anesthetized Microelectrode Mapping

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