1. Neuromuscular integration Tom Burkholder thomas.burkholder@ap.gatech.edu 4-1029 Weber 123 http://www.ap.gatech.edu/burkholder/8813http://www.ap.gatech.edu/burkholder/8813/

2. Learning goals Technical –Frog anatomy –Muscle mechanics –Force transducer –Feedback control Conceptual –Muscle physiology –Proprioceptors –Sensorimotor integration Develop a closed loop hybrid system to investigate some aspect of neuromuscular control. Ideally, the structure or parameters of the computational system will test a model of biological control

3. References Gasser HS and Hill AV. The dynamics of muscular contraction. Proc R Soc Lond (B) 96: 398-437, 1924. Rack PM and Westbury DR. The effects of length and stimulus rate on tension in the isometric cat soleus muscle. J Physiol (Lond) 204: 443-460, 1969. Nichols TR and Houk JC. Improvement in linearity and regulation of stiffness that results from actions of stretch reflex. J Neurophysiol 39: 119-142, 1976. McCrea DA. Spinal circuitry of sensorimotor control of locomotion. J Physiol 533: 41-50, 2001. Lutz GJ and Rome LC. Built for jumping: the design of the frog muscular system. Science 263: 370-372, 1994. Rome LC, Swank D, and Corda D. How fish power swimming. Science 261: 340-343, 1993. Chizeck HJ, Crago PE, and Kofman LS. Robust closed-loop control of isometric muscle force using pulsewidth modulation. IEEE Trans Biomed Eng 35: 510-517, 1988.

4. Control of Motion Phylogenic background Motor proteins Muscle properties Control systems

5. Protista motility RNA Polymerase Mitosis Swimming –Flagella –Cilia Crawling –Rolling –Pseudopod formation Chemotactic Receptor mediated activation of myosin

6. Nematodes Large scale swimming –Cyclical –Force/motion phase Specialized organs –Sensors –Motors –Wiring Complex behavior –Avoidance Muscle activation

7. Insect Flight Indirect flight muscles Activated less than once per cycle Molecular kinetics Springlike, but positive work Stretch activation Stimulation Active force Passive force Applied length

8. Mammalian locomotion Multiple limbs Ballistic

9. Muscular work during gait Positive work Passive elastic mechanisms Daley, M. A. et al. J Exp Biol 2003;206:2941-2958

10. Terrestrial posture Support body against gravity Perturbation control –External (wind) –Internal (respiration, muscle) Small movements

11. Motor proteins Kinesin, dynein, myosin Globular head –Filament binding & ATPase Cargo-carrying tail Myosin Kinesin

12. Myofilament structure Myosin polymers arrange motor domains to maximize interaction with actin filament 200 nm

13. Structural homogeneity Structural order yield functional consistency –Narrow range of sarcomere “strength” –Minimizes intra-muscular force loss

14. Sliding filament theory Force varies in proportion to crossbridge binding IAIZ

15. Crossbridge cycle ATP driven, ratchet motion Mechanochemical coupling by crossbridge elasticity

16. Crossbridge Cycle Myosin binds actin strongly (rigor) ATP binding to myosin displaces actin Hydrolysis of ATP energizes myosin; moves crossbridge Energized myosin binds actin Release of inorganic phosphate triggers power stroke

17. Fundamental reactions Actin-myosin association –Slow (20 ms) –All or none change in force Power stroke –Fast (1 ms) –Modulatory A rapid shortening pushes crossbridges through the power stroke. These crossbridges rapidly accommodate the change and are slowly displaced by new crossbridges

18. Isotonic shortening Muscle can shorten against less load than it can hold. Stimulate muscle Allow force to stabilize Release against constant load Magnetic catch Muscle Counterweight

19. Dynamic response of muscle Isotonic force velocity relation Stretch and hold response -0.500.51 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 Po Vmax Shortening Velocity Force Force (mN) Time (ms) 0100200300400 D L (mm) 0 0.2 0 500 10000 Force response Applied length

20. Engineering analog “Force-length” is like stiffness “Force-velocity” is like viscosity -0.500.51 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 Po Vmax Shortening Velocity Force F=Fo-bv F=kx

21. Phenomenological (Hill) Model Linear model –Force-length spring constant –Force-velocity viscosity Standard linear solid analogy –Contractile Force-length –Contractile Force-velocity –Elastic elements account for dynamics

22. Control of activation Troponin/tropomyosin complex –Bind actin –Block myosin –Calcium dependent

23. Calcium control Contractile dynamics are calcium dependent Efficient contraction requires homogeneous calcium transients Sarcoplasmic reticulum T-Tubules

24. Excitation contraction coupling Synaptic discharge initiates action potential V-gated Ca2+ channels open Ca2+ bind TnC Force generation Recovery Action potential Calcium Force

25. Force summation Nonlinear addition of subsequent APs

26. Force Frequency Muscle & species dependent Myosin kinetics Calcium kinetics

27. Whole muscle organization Physical –Fiber –Fascicle –Muscle –Agonist Neural –Motor unit –Compartment –Muscle –Synergy

28. Motor Unit Alpha motorneuron –Large (12-20 um) –High CV (70-120 m/s) Innervated muscle fibers –10-1000 fibers/neuron –Generally proportional to axon size –Generally of similar function 5-1000s per muscle Innervated fibers MN

29. Whole muscle force modulation Rate –Force-frequency –Continuous control Recruitment –Select subpopulation of MU –Force sharing –Metabolic optimization –Size principle

30. Motor unit control Smooth force generation –Individual MUs sub- tetanic –Rate & phase variation

31. Electrical stimulation Recruitment –Axonal input resistance –Capacitance Synchrony Recruitment modulation –Intensity –Pulse width –High frequency block