Transcript 3FA3M8-C

Strengthening of horizontal
cortical connections
following skill learning
Rioult-Pedotti, M. S., et al. (1998)
Commentary by:
Brian Prinzen
Emine Duygu Nangir
Zachary Saadon
Anteneh Kassa
Zach Saadon
Outline
Summary
 Pros
 Methodological Critique


Synaptic Changes
Contradicting Evidence
 Future Implications
 Conclusion

Zach Saadon
Summary - Hypothesis
 Motor
skill learning
strengthens horizontal
connections in rat M1
using an LTP-like
mechanism
Zach Saadon
Summary - Methods
Training condition
 Paired controls
 Unpaired controls
 Ipsilateral control
 Forelimb vs. hindlimb
 Field potentials recorded using glass
micropipettes placed in layer II/III of M1
slice

Zach Saadon
Summary – Results

Field Potentials:

Trained M1 > Untrained
 Trained > Control
 Hindlimb region showed
no amplitude difference
Zach Saadon
Summary - Conclusions
 The
learning of a motor skill engages
an LTP-like process – thus mediating
the strengthening of horizontal
cortical connections
Zach Saadon
Pros
Right handed rats
 Use of multiple controls
 Testing for electrically induced LTP

Synaptic Changes
Brian Prinzen
Brian Prinzen
Synaptic Changes METHODOLOGY

Pyramidal arrangement of
motor skills

A combination of previously
known motor skills

A complex motor skill is often
composed of a fixed sequence of
movements

Hikosaka et al.
Brian Prinzen
Synaptic Changes METHODOLOGY

Changes represent a new motor skill or
an adaptation and combination of
previously learned motor skills?

“These tasks may be considered forms of motor-skill learning because the
motor actions appear to have required the acquisition of novel
spatiotemporal muscle activity patterns, but they also include forms of
adaptation. It remains a challenge to evaluate whether modifications
following this type of learning reflect the process of learning or altered motor
actions”

Sanes and Donoghue (2000)
Brian Prinzen
Synaptic Changes IMPLICATIONS


No denying the change in
synaptic efficacy
Too quick to interpret data

“we currently have no idea how
increases in synaptic efficacy among
the horizontal connections of the
forelimb region of M1 can encode a
complex spatiotemporal sequence of
movements”


Martin and Morris, 2001
Do changes represent actual
motor program engram or
some auxiliary information
processing purpose?
Brian Prinzen
Synaptic Changes IMPLICATIONS

If novel motor action produced changed in synaptic
efficacy in left brain, why do we not see any changes in
right brain?

Left forelimb performed “new motor skill”, but no change
in right M1

“The difference between untrained M1 and left and right M1 of
controls was not significant.”


Rioult-Pedotti et al.
Evidence for lack of novelty and synaptic change
representing information processing

Whether the precise pattern of changes in synaptic strengths
constitutes and engram of the motor program for the execution of
the task, or whether such changes have some ancillary
information processing role.”

Martin and Morris, 2001
Contradictory
Evidence
Anteneh Kassa
Anteneh Kassa
Contradictory Evidence

Skilled motor learning does not enhance longterm depression in the motor cortex in vivo
(Castro & Cohen, 2004)

AIM- Investigate how learning a reaching task
affects excitability, short-term, & long-term
plasticity
Anteneh Kassa
Contradictory evidence
RATIONAL
learning is expected to produce bidirectional changes while stress produces
uni-directional changes
 METHOD
compare food deprived trained rats with
food deprived untrained rats and naïve
controls

Anteneh Kassa
Results
Cohen, J. D. et al. J
Neurophysiol 93:
1486-1497, 2005
Anteneh Kassa
Results
LFS to induce LTD
 Controls had
significantly lower
levels of LTD
 Food deprivation
resulted in increased
LTD in the other
groups

Anteneh Kassa
What’s going on?

Why was there no difference in excitability
between trained and untrained
hemispheres?

Why did the slice studies not reveal an
effect of food deprivation and handling on
LTD?
Anteneh Kassa
Look for LTP in spinal cord
neurons
Central pattern
generators
 Neurons in the spinal
cord receive
projections from the
motor cortex
 Measure field
potentials

Anteneh Kassa
Suggestions for methodology

Compare the effects of food deprivation

Look for LTP in spinal cord neurons

Include a group that was administered
NMDA antagonists and measure learning
ability
Further Implications
Duygu Nangir
Duygu Nangir
Further Implications

LTP processes have been correlated to
symptoms of Schizophrenia, Parkinson’s
and Alzheimer's and may be involved in
these neurodegenerative disorders.
 Are

related to disrupted plasticity in the cortex
There has been many studies that relate
LTP to these neurodegenerative disorders,
including those that are involved in motor
learning and other processes
Duygu Nangir
Further Implications

Direct evidence of LTP motor learning in
Schizophrenia

Concludes that:

SCZ patients revealed a correlation between LTP with
motor skill learning; the deficit in learning & memory in
SCZ may be acting through or dependent of a
disconnected LTP
 Association between LTP-like plasticity & motor skill
learning suggestion that a disruption of neural plasticity
may underlie the deficits in learning & memory and in the
actual disorder of Schizophrenia

Frantseva et. al, 2007
Duygu Nangir
Further Implications
Article topic:
What they set to
prove (purpose)
Conclusion
Relation to LTP and
motor learning
Age-Dependent
Modulation of
Hippocampal LongTerm Potentiation by
Antioxidant Enzymes
(Journal of
Neuroscience
Research, 2006)
examine
observations
oxidative
the effects of
the antioxidant
enzymes, which produce
and remove H2O2,
respectively, on LTP
forms of synaptic
plasticity during aging.
suggest
that both O2 and H2O2
also play a positive
facilitatory role in LTP
forms of synaptic
plasticity in the
mammalian
hippocampus
stress is
associated with aging &
neurodegenerative
disorders [Alzheimer's,
Parkinson’s]
since LTP has age
related deficits, factors
all link to LTP &
symptoms are motor
deficits
Interference of
find the evidence of
results show that
copper suppresses LTP,
chronically ingested
copper interaction in
copper reduces
maintaining the function
copper in long-term
LTP, stimulated by
synaptic sensibility.
of synaptic traffic –
potentiation (LTP)
copper involvement in
These effects represent copper blocks the
of rat hippocampus
neurodegenerative
a significant
receptors in LTP
(Brain Research, 2005) illness, like Parkinson, & disturbance in the
Affect synaptogenesis,
Alzheimer.
plasticity phenomenon learning & memory
associated with
(learning motor skills are
learning and memory
symptoms of disorders)
Duygu Nangir
Conclusion
Relating to the Article
Pros
(good, correlating parts
of the study)
1.
2.
3.
Cons
(what could have been
done better)
1.
2.
Suggestions
(what can be changed
to improve the study)
1.
Discussion
(how this study has
affected future studies)

2.
Use right-handed rats (creates a good control)
Use multiple controls (ipsilateral vs. contraleral; trained vs.
paired; trained vs. naïve; hind-limb vs. fore-limb)
Testing for electrically induced LTP
We can't deny the presence of changes in synaptic
pathways, but we need to evaluate if they are due to the
learning of a new motor skill or just the adaptation of old
skills
LTP is bi-directional (not uni-) in LTP & LTD; no LTD+rats
show LTP from stress & food deprivation
Use NMDA antagonists & measure ability to induce LTP ex
vivo (M1 relies on NMDA for LTP)
Since M1 neurons are connected to neurons in spinal cord,
they can measure LTP in spinal cord
Motor learning deficits have been correlated to
neurodegenerative disorders that involved LTP-like plasticity in
the brain

Neurodegenerative disorders: Schizophrenia, Alzeihemer’s &
Parkinsons
References
Rioult Pedotti, M.S., Friedman, D., Hess, G., Donoghue, J.P., (1998). Strengthening of
horizontal coritcal connections folowing skill learning. Nature, 1(2), 230-234
Martin, S.J., Morris, R.G.M. (2001). Cortical Plasticity: It’s All the Range! Current Biology,
11, R57-R59
Rioult-Pedotti, M. S., Friedman, D., & Donoghue, J. P. (2000). Learning-induced LTP in
neocortex. Science (New York, N.Y.), 290 (5491), 533-536.
Cohen, J.D., & Castro, M.A. (2004). Skilled motor learning does not enhance long-term
depression in the motor cortex in vivo. Journal of Neurophysiology. (Bethesda MD),
93, 1486-1497
Goldschmith, et al. (2005). Interference of chronically ingested copper in long-term
potentiation (LTP) of rat hippocampus. Brain Research, 1056 (2), 176-82
Watson, et al. (2006). Age-dependant modulation of hippocampal long-term potentiation
by antioxidant enzymes. Journal of Neuroscience Research, 84, 1564-1574
Frantseva, et al. (2008). Evidence for impaired long-term potentiation in schizophrenia
and its relationship to motor skill learning. Cerebral Cortex, 18 (5), 990-6
Sanes, J.N., Donoghue, J.P. (2000). Plasticity and Primary Motor Cortex. Annual Review
of Neuroscience, 23, 393-415
Hikosaka, O., Nakamura, K., Sakai, K., Nakahara, H. (2002) Central Mechanisms of
Motor Skill Learning. Current Opinion in Neuroscience.12 217-222
Questions?