Strengthening of horizontal cortical connections following skill learning

1. 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

2. Zach Saadon Outline • Summary • Pros • Methodological Critique • Synaptic Changes • Contradicting Evidence • Future Implications • Conclusion

3. Zach Saadon Summary - Hypothesis • Motor skill learning strengthens horizontal connections in rat M1 using an LTP-like mechanism

4. 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

5. Zach Saadon Summary – Results • Field Potentials: • Trained M1 > Untrained • Trained > Control • Hindlimb region showed no amplitude difference

6. Zach Saadon Summary - Conclusions • The learning of a motor skill engages an LTP-like process – thus mediating the strengthening of horizontal cortical connections

7. Zach Saadon Pros • Right handed rats • Use of multiple controls • Testing for electrically induced LTP

8. Synaptic Changes Brian Prinzen

9. 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.

10. 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)

11. 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?

12. 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

13. Contradictory Evidence Anteneh Kassa

14. Contradictory Evidence Anteneh Kassa Skilled motor learning does not enhance long-term depression in the motor cortex in vivo (Castro & Cohen, 2004) AIM- Investigate how learning a reaching task affects excitability, short-term, & long-term plasticity

15. Contradictory evidence Anteneh Kassa RATIONAL learning is expected to produce bi-directional changes while stress produces uni-directional changes METHOD compare food deprived trained rats with food deprived untrained rats and naïve controls

16. Results Anteneh Kassa Cohen, J. D. et al. J Neurophysiol 93: 1486-1497, 2005

17. Results Anteneh Kassa LFS to induce LTD Controls had significantly lower levels of LTD Food deprivation resulted in increased LTD in the other groups

18. What’s going on? Anteneh Kassa 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?

19. Look for LTP in spinal cord neurons Anteneh Kassa Central pattern generators Neurons in the spinal cord receive projections from the motor cortex Measure field potentials

20. Suggestions for methodology Anteneh Kassa 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

21. Further Implications Duygu Nangir

22. Further Implications Duygu Nangir • 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

23. Further Implications Duygu Nangir • 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

24. Further Implications Duygu Nangir

25. Conclusion Duygu Nangir

26. 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

27. Questions?