1. SECTION #1 Continued Motoneurons and Local Circuits (Group #1)

2. Review: General Control Theory We’ll finish up local and “lower” MNs today, as well as discuss brain- stem pathways: -reflexes -CPGs -Models

3. Current Research Topics Historically, any patterned behaviour was termed a “reflex.” What is a reflex? What are the defining characteristics of a reflex? There was a time when reflexes were to be feedback circuits.

4. Current Research Topics Many patterned motor actions are loosely independent of sensory feedback. Circuits that produce a patterned output (unchanging) and do not involve sensory integration are referred to as feedforward.

5. Current Research Topics - It remains unclear to what extent reflexes such as the H-reflex control muscle tone during normal postural events and holistic changes in position. - Sign change in activation / inactivation of reflexes: mechanism is partially understood, but upstream controller isn’t. - There is an important distinction between tonic and phasic postural events and systems. Jane MacPherson in cat

6. Local Circuits: CPGs Central Pattern Generators: - Oscillatory circuits… “Push – Pull” - Responsible for appropriate coordination of flexion and extension during locomotion - Each limb has own in primate, and presumably human check out: http://www.bio.brandeis.edu/biomath/mike/net_osc.html Limb Position Extensor Flexor

7. CPGs Continued Sources of Modulation: - Local Circuits- Propriospinal pathways - Descending inhibition coordinate upper & lower limbs - Afferent input (1b)- STATE! experimental disruption

8. CPGs Continued Clinical Implications: - Some patients with partial spinal damage have been able to regain limited motor control with a combination of: - psychological training (readiness?) - electrical repetitive stimulus directly to the lower spinal cord - extensive physical training (Jane MacPherson: cat) - Our understanding of autonomous behaviors has improved - stroke patients are better guided to bi-lateral modality - Local applications of pharmacology? - NMDA

9. Now that you have an introduction to the SIMPLEST elements of motor control: what do you see happening here?

12. Appropriate Models… How can we improve the prognosis of spinal patients? As mentioned, quantitative evaluations of neural networks CANNOT, or as of yet, HAVE NOT taken place in human: Every model has some implicit limitation; it is only an approximation of the system of interest. - Computer models - “Lower” Species - primates (new and old world monkeys) - cat - lamprey - crustacean - Inference-based reasoning - from clinical trials

13. Appropriate Models Continued Why in the world work on a hermit crab (or ANY model)? 1)Clearly observable, measurable, and simple behavior 2)Robust preparation (survivability) 3)No vertebrate ethics committees

14. Appropriate Models Continued Why in the world work on a hermit crab? It’s a simple system, with so few components, that we can compute circuit / model equations with some precision. Compared to its phylogenetically close relatives, the hermit crab’s abdominal motor control system has fewer premotor elements

15. Appropriate Models Continued Why investigate model species? Answer: If a crab is this complicated, then imagine the human models.

16. SECTION #2 Brainstem and Motor Cortex (Group #2a)

17. Brainstem Indirect Pathways Indirect Pathways: ~semi-autonomous -to proximal muscles -maintain an initiated motor behavior -some amount of brainstem “processing” Direct Pathways Direct Pathways: ~primarily voluntary -fine movement -distal muscle groups

18. Brainstem Continued Consists of multiple “centers” or nuclei It is within these loci that integration / processing takes place We will discuss some: indirect pathways - Superior Colliculus (eyes, not to inferior sp. cord) - Vestibular Nuclear Complex (balance) - Reticular Formation (postural coordination) - Red Nucleus (generally associated with direct pathways*) * though direct pathways also refers to M. Cortex to spinal cord

19. Brainstem Continued indirect pathways Vestibular Nucleus : - Posture / Body Position - Compensatory (rapid but only post-event) - Input: 8th C.N. = Aud. / Vestibular - Output: medial spinal cord gray matter - Some output to more lateral sections controls proximal set of ‘limb muscles’

20. Brainstem Continued indirect pathways Reticular Formation: - Body Stability During Movement (also respiration, heart rate, and other functions) - feedforward / RT integrative control - neuron clusters intertwined with passing axons - Input: cortex / other brainstem centers - Output: primarily medial spinal gray matter

21. Brainstem Continued direct pathways Red Nucleus : - Fine movements (direct pathway) - Feedforward mechanism stabilizes body during movements - Inputs: Motor cortex - Output: act on lateral spinal gray matter & local circuits in spinal cord

22. Decussate: To cross the midline Brainstem Continued indirect pathways

23. Brainstem Continued direct pathways Rubrospinal: via the Red Nucleus

24. An example… reticulospinal likely the action of a reticulospinal pathway corticospinal rubrospinal could be the action of a corticospinal or rubrospinal pathway

25. An example… INDIRECT PATHWAY DIRECT PATHWAY

26. What occurs upon hand contact? 1) The  MN innervates what muscle? 2) What sensory fiber is involved? 3) Where are these cells?

27. Local Sensitivity - Medial (gross) walking, sitting - Lateral (fine) piano, spoons Clinical Implications Partial Lesions Section Level “relative severity” OK Sacral: OK (why?) Bad Cervical/Thoracic: Bad (why?) 50/50 Lumbar: 50/50 (why?)

28. Current Research Topics Where is control of simple postural commands (Cat; MacPherson J):

29. Current Research Topics Determining the necessary signals (Bizzi E):

30. Brainstem and Motor Cortex (Group #2b)

31. Primary Motor Cortex - Pre-Central Gyrus - Identification by stimulus response and morphology

32. Primary Motor Cortex - Mostly direct pathways, some indirect pathways D: dorsolateral pathways to lateral sp. cord via red nucleus (functions?) I: ventromedial pathways to medial sp. cord via reticular formation (functions?) - Does 1° motor cortex encode whole movement? not individual muscles not vectors  command neurons

33. Homunculus Rough Estimate; great diversity Topographical Orientation: Primary M. Cortex Continued

34. Directionality : yellow = one cell’s firing vectors (broad) red = “best” vector No one (1) cell can generate an appropriate directional code! Population Tuning

35. Current Research Topics How is the vertebrate spinal cord arranged? Could it be by function (Bizzi E):

36. PreMotor Cortex - Rostral Pre-Central Gyrus - Activated by cues for well-learned events (monkey) PreMotor Cortex

37. PreMotor Cortex Continued Lateral PreMotor elements - conditional tasks - fire before action - external cues (in monkey anyway) - damage = inability to select appropriate response movements Medial PreMotor elements - initiate internally / voluntarily driven motor tasks - internal cues - damage = reduced spontaneous movements

38. Review: Pathways Be familiar with the contribution of each particular anatomical structure / region: -Cortex 2 regions discussed -Brainstem the 3 nuclei discussed & pathways -Spinal Cord spatial significance / distribution -Local Circuitry / MNs / Muscle those properties discussed