Strengthening of Horizontal Cortical Connections Following Skill Learning M.S. Rioult-Pedotti, D. Friedman, G. Hess & J.P. Donoghue Presented by Group

Strengthening of Horizontal Cortical

Connections Following Skill Learning

Strengthening of Horizontal Cortical

Connections Following Skill Learning

M.S. Rioult-Pedotti, D. Friedman, G. Hess & J.P.

Donoghue

M.S. Rioult-Pedotti, D. Friedman, G. Hess & J.P.

DonoghuePresented by Group B5

Nidhi Bhushan, Marry Fernandez, Amina Nawaz, Rachel Wallace and

Rory Wasserman

Presentation OutlinePresentation Outline

Background Information

Aims of Study

Methods and Procedures

Results & Conclusions

Significance of Study

Background Information

Aims of Study

Methods and Procedures

Results & Conclusions

Significance of Study

Background InformationBackground Information

BACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GCR, Kasai H.2008. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 310:1683–6

Nihdi

LTP the increasing sensitivity of synapses over

time, producing a larger postsynaptic output

Shown to result in growth of new, rapidly

functional filipodia/spines

Learning & memory

Synaptic plasticity

LTP the increasing sensitivity of synapses over

time, producing a larger postsynaptic output

Shown to result in growth of new, rapidly

functional filipodia/spines

Learning & memory

Synaptic plasticity



Nidhi

M1: generates neural impulses to control

execution of movement

Horizontal connections between layer II

and III capable of LTP

Suggests LTP can modify horizontal

connection strength as a new motor skill

is learnt

M1: generates neural impulses to control

execution of movement

Horizontal connections between layer II

and III capable of LTP

Suggests LTP can modify horizontal

connection strength as a new motor skill

is learnt

History of TopicHistory of Topic

Charles Sherrington - Term “Synapse”

Ramon y Cajal - Synaptic Connection Pavlov - Classical Conditioning

Donald Hebb - Fundalmental Associative Mechanism

Terje Lomo - Experimentally discovered LTP

Richard Morris - 5 Fundamental Properties of LTP

Donoghue, et al. - Acquisition of Motor Behaviour

Charles Sherrington - Term “Synapse”

Ramon y Cajal - Synaptic Connection Pavlov - Classical Conditioning

Donald Hebb - Fundalmental Associative Mechanism

Terje Lomo - Experimentally discovered LTP

Richard Morris - 5 Fundamental Properties of LTP

Donoghue, et al. - Acquisition of Motor Behaviour


Rachel

Textbook cite needed

Purpose of StudyPurpose of StudyBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Rachel

Researchers claimed that there was no previous studies explicitly showing: M1 circuitry changes with learning Evidence of physical modifications of neurons i.e. increasing dendretic spines really do improve cortical connections

LTP type mechanisms are used to acquire new motor skills

Researchers claimed that there was no previous studies explicitly showing: M1 circuitry changes with learning Evidence of physical modifications of neurons i.e. increasing dendretic spines really do improve cortical connections

LTP type mechanisms are used to acquire new motor skills

Rioult-Pedotti, M.S., Friedman, D., Hess, G. and Donghue, J.P. (1998). Strengthening of horizontal cortical connections following skill learning. Nature

Neuroscience 1(3), 230-234.



Rachel

What is a Field Potential?

An electrical recording visually demonstrating the electrical connectivity between synapses

Extracellular EPSP (excitatory pre-synaptic potential) field potential demonstrate the strength of that cell with the next horizontal intracortical cell as it is thought that learning is accompanied by changes in the strength of those very connections

What is a Field Potential?

An electrical recording visually demonstrating the electrical connectivity between synapses

Extracellular EPSP (excitatory pre-synaptic potential) field potential demonstrate the strength of that cell with the next horizontal intracortical cell as it is thought that learning is accompanied by changes in the strength of those very connections

Rioult-Pedotti, M.S., Friedman, D., Hess, G. and Donghue, J.P. (1994). Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps. Journal of Neurophysiology 71(6), 2543-2547.

Aim of StudyAim of StudyBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Rachel

Aim Discover empirical evidence that when learning a new motor skill cortical synapses alter and strengthen their connections

Aim Discover empirical evidence that when learning a new motor skill cortical synapses alter and strengthen their connections



Experiment OneExperiment OneBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Amina

Investigated relationship between acquisition of new motor behaviour and horizontal cortical connection strength Rats were trained in a

skill reaching task involving only one forelimb over 3 to 5 days

Two sets of controls were used: paired and unpaired

Investigated relationship between acquisition of new motor behaviour and horizontal cortical connection strength Rats were trained in a

skill reaching task involving only one forelimb over 3 to 5 days

Two sets of controls were used: paired and unpaired

UNTRAINED


Amina

Trained skill: reaching for food pellet task

Trained skill: reaching for food pellet task

http://www.youtube.com/watch?v=NZwM9bop02w


Amina

Horizontal cortical connection strength was measured using coronal brain slices of both hemispheres Trained M1: hemisphere

contralateral to trained forelimb

Untrained M1: hemisphere contralateral to untrained forelimb

Controls: the two hemispheres were termed "Left M1" and "Right M1"

Horizontal cortical connection strength was measured using coronal brain slices of both hemispheres Trained M1: hemisphere

contralateral to trained forelimb

Untrained M1: hemisphere contralateral to untrained forelimb

Controls: the two hemispheres were termed "Left M1" and "Right M1"

LeftRight


Amina

Symmetrically-placed stimulating and recording microelectrodes in layer II/III Horizontal Connections measured field potential

Compared amplitudes of field potentials in each hemisphere, for both forelimb and hindlimb regions

Symmetrically-placed stimulating and recording microelectrodes in layer II/III Horizontal Connections measured field potential

Compared amplitudes of field potentials in each hemisphere, for both forelimb and hindlimb regions


Amina

QuickTime™ and a decompressor

are needed to see this picture.

1) Brain slices containing the Primary Motor Cortex (M1)

2) Devices were placed accordingly:

Recording Devices:Glass micropipettes within the same relative receptor field in the II/III layer

Stimulating Devices:Concentric bipolar stimulating electrodes placed on either side of the recording electrodes

1) Brain slices containing the Primary Motor Cortex (M1)

2) Devices were placed accordingly:

Recording Devices:Glass micropipettes within the same relative receptor field in the II/III layer

Stimulating Devices:Concentric bipolar stimulating electrodes placed on either side of the recording electrodes

Measuring Strength of Cortical Connections







Amina

3) Currents were delivered

through the stimulating devices exciting the receptor cell

4) Field potentials were

measured and their

amplitudes were compared

to determine relative strengths

3) Currents were delivered

through the stimulating devices exciting the receptor cell

4) Field potentials were

measured and their

amplitudes were compared

to determine relative strengths

QuickTime™ and a decompressor

are needed to see this picture.



Experiment TwoExperiment TwoBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Amina

Investigated relationship

between stimulus intensity and

response amplitude Clarify if rat response

intensities in M1 were: Due to skill learning

OR

Due to the specific stimuli used to

evoke field potentials?

Investigated relationship

between stimulus intensity and

response amplitude Clarify if rat response

intensities in M1 were: Due to skill learning

OR

Due to the specific stimuli used to

evoke field potentials?


Amina

Method 1: Constant Fraction Rats tested with stimuli that were a

FRACTION of the maximum response

intensity

Method 2: Constant Multiple Rats tested with stimuli that were a

MULTIPLE of the minimal response

intensity

Method 1: Constant Fraction Rats tested with stimuli that were a

FRACTION of the maximum response

intensity

Method 2: Constant Multiple Rats tested with stimuli that were a

MULTIPLE of the minimal response

intensity


Amina

Logarithm of the response-

amplitude ratio between groups at

each stimulation intensity Compared trained and untrained rats

Compared M1 from left and right

hemispheres

WHY? To observe differences easier

I.e. If difference = 0, ratio = 1;

thus, the log ratio = 0

Logarithm of the response-

amplitude ratio between groups at

each stimulation intensity Compared trained and untrained rats

Compared M1 from left and right

hemispheres

WHY? To observe differences easier

I.e. If difference = 0, ratio = 1;

thus, the log ratio = 0

ResultsResultsBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Rory

Field potentials evoked in the trained M1

were larger in amplitude than those

evoked in the untrained M1

Evoked at 60% max. stimulation intensity

Field potentials evoked in the trained M1

were larger in amplitude than those

evoked in the untrained M1

Evoked at 60% max. stimulation intensity

Single Case Population AverageSingle Case Population Average


Rory

Stimuli is a

constant multiple

of the min. stimulus intensity

(12-30µA)

Stimuli is a

constant multiple

of the min. stimulus intensity

(12-30µA)

Avrg. Response is larger for the trained M1 at every

stimulus intensity

Avrg. Response is larger for the trained M1 at every

stimulus intensity

Max. intensity = 220µA



Rory

Black circles: Log (trained M1/untrained M1) White circles: Log (left M1/right M1)

Log ratio of 0 means there is no difference between the two hemispheres

Black circles: Log (trained M1/untrained M1) White circles: Log (left M1/right M1)

Log ratio of 0 means there is no difference between the two hemispheres

Stimuli is a constant

multiple of the min. stimulus

intensity (12-30 µA)

Stimuli is a constant

multiple of the min. stimulus

intensity (12-30 µA)




Rory

• Histogram for the entire data set

• There is a shift towards the trained M1

• Control has not shifted, neither hemisphere shows a difference

• Histogram for the entire data set

• There is a shift towards the trained M1

• Control has not shifted, neither hemisphere shows a difference


Rory

Clear amplitude difference between the trained and untrained M1 at evey stimulation intensity

The log difference between the hemispheres showed a shift towards the trained M1

Increased excitability of the trained M1

Is this caused by LTP?

Clear amplitude difference between the trained and untrained M1 at evey stimulation intensity

The log difference between the hemispheres showed a shift towards the trained M1

Increased excitability of the trained M1

Is this caused by LTP?


Rory

Occlusion Test If the increased

postsynaptic excitability is due to LTP, further LTP will be difficult to induce

Arrows indicate LTP induction

In the control, both hemispheres were induced equally

Occlusion Test If the increased

postsynaptic excitability is due to LTP, further LTP will be difficult to induce

Arrows indicate LTP induction

In the control, both hemispheres were induced equally

But in the trained condition LTP was induced much more readily in the untrained M1LTP of the trained M1 was occludedPresumably because LTP has already occurred

But in the trained condition LTP was induced much more readily in the untrained M1LTP of the trained M1 was occludedPresumably because LTP has already occurred

Significance & SummarySignificance & SummaryBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Rory

This experiment demonstrated plasticity in the motor cortex following skill learning

Larger amplitude observed in the trained M1, may be due to an increase in horizontal connections between cells

Based on the occlusion test, this affect was at least partly based on LTP or LTP-like mechanism

First direct evidence that plasticity of the intracortical connections is associated with learning motor skills

This experiment demonstrated plasticity in the motor cortex following skill learning

Larger amplitude observed in the trained M1, may be due to an increase in horizontal connections between cells

Based on the occlusion test, this affect was at least partly based on LTP or LTP-like mechanism

First direct evidence that plasticity of the intracortical connections is associated with learning motor skills

ReferencesReferencesBACKGROUNDAIMS OF STUDYMETHODSCONCLUSIONSSIGNIFICANCE

Rory

Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GCR, Kasai H.2008. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 310:1683–6

Rioult-Pedotti, M.S., Friedman, D., Hess, G. and Donghue, J.P. (1998). Strengthening of horizontal cortical connections following skill learning. Nature Neuroscience 1(3), 230-234.

Rioult-Pedotti, M.S., Friedman, D., Hess, G. and Donghue, J.P. (1994). Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps. Journal of Neurophysiology 71(6), 2543-2547.

Documents

Strengthening of Horizontal Cortical Connections Following Skill Learning M.S. Rioult-Pedotti, D. Friedman, G. Hess & J.P. Donoghue Presented by Group