1. Neural and Sensory Efferent innervation – Neuromuscular junction –  -,  -motorneurons Afferent innervation – Muscle spindle – Golgi tendon organ

2. Overview Motor Unit – Motorneuron + many muscle fibers – Cholinergic synapse Spindle – Enapsulated, specialized muscle-like cells – Combined length-velocity proprioception Tendon organ – Nerve endings woven through collagen – Active tension mechanorecption

3. Efferent Innervation a-motorneuron – 100 um cell body/soma Ventral horn of spinal cord Columnar organization by muscle – 8-18 um diameter axon 60-120 m/s conduction velocity Terminal branches within target muscle – Dendritic tree 10,000+ inputs per MN Excitatory glutamic synapses Inhibitory glycinergic/GABAergic synapses Dorsal/posterior Ventral/anterior MN density Cervical Thoracic Lumbar Sacral Arm/hand Leg/foot

4. Neuromuscular junction Motor endings – Synaptic vessicles – Mitochondria Synaptic cleft – Primary – Secondary invaginations Muscle – Post-synaptic density – Mitochondria deHarven & Coers, 1959

6. By SEM Sohn & al., 1999

7. Synaptic vessicle anchoring SV anchored by “pegs and ladders” Harlow & al., 2000

8. Synaptic structure Complementary – Presynaptic active zone – Postsynaptic density/receptor ECM coordination – Nerve  agrin  MuSK – Muscle  Lam 421/521  VGCC Electrical coordination – Nerve: ubiquitinylation preserves synaptotagmin – Muscle: depolarization degrades AChR

9. Presynaptic side Docking site – SNAP-25 – Syntaxin (T-SNARE) Synaptic vesicle – Synaptobrevin (V-SNARE) – Synaptotagmin Docking trimer: t/v-SNARE+SNAP Calcium sensitivity: synaptotagmin

10. Presynaptic active zone De Wit & al., 2009

11. Presynaptic active zone Garner 2002

12. Postsynaptic side Post-synaptic density – MuSK/LRP4 receptor – Rapsyn/Dok-7 adapter – Src kinase – Acetylcholine receptor Junctional folds – Sodium channels – Acetylcholinesterase

13. Post-synaptic density Shi & al., 2012

14. Afferent innervation Afferent – Sensory – Dorsal root ganglion – Synapses in SC Spindle – Muscle-like cells – Mechanosensitive nerve ending

15. Muscle Spindle Capsule Polar regions –  -motorneurons – Striated contractile proteins Equatorial region – Primary afferent (Ia) – Secondary afferent (II) – Non-contractile – Nuclear bag & chain Barker, 1948

16. Spindle afferents Barker, 1948

17. Spindle efferents Dynamic bag/bag1 – Usually only influences the primary ending – Increases velocity gain Static bag/bag2 – Offset both primary & secondary – Reduces length sensitivity of primary Chain – Take up slack – Increase length sensitivity of secondary

18. Spindle Mechanics Equatorial stretch induces depolarization – Windings amplify length change – Stretch imposed from outside – Stretch imposed by contraction of poles Accommodation – Viscoelastic creep/relaxation – Primary fast: velocity – Secondary slow: length

19. Stretch response Primary ending Houk & al, 1981 Secondary ending Afferent firing rate Muscle length

20. Ian Boyd video clip

21. Stretch Reflex Ia afferent  “homonymous” motorneuron – Servo-like length control – Tendon tap – Vibration illusions Ia  Ia interneuron – Inhibit antagonist(s) – Mechanical equivalence – Myotatic unit II  dorsal horn interneurons – Distributed, slower excitation

22. Golgi tendon organ Free nerve endings embedded in capsule at muscle-tendon interface Group Ib Nitatori, 1988

23. Goldfinger & Fukami 1982

24. GTO response MTJ tension depolarizes afferent Muscle length Muscle force GTO discharge rate Crago & al., 1982

25. GTO Reflex Ib  Ib interneuron – Delayed homonymous inhibition – Distributed excitation/inhibition – “Interaction” torques – Locomotor pattern integration Polysynaptic pathways are subject to extra modulation

26. Summary  -motorneuron efferent forms coordinated NMJ – Presynaptic active zone for ACh release – Postsynaptic densities for ACh transduction Monosynaptic stretch reflex – Combined length and velocity signal – Intrafusal fiber mechanics mimic extrafusal fibers Polysynaptic GTO reflex – Force feedback – Distributed