Neural and Sensory

• Efferent innervation– Neuromuscular junction– -, -motorneurons

• Afferent innervation– Muscle spindle– Golgi tendon organ

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

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/anteriorMN

densityCervical

Thoracic

Lumbar

Sacral

Arm/hand

Leg/foot

Neuromuscular junction

• Motor endings– Synaptic vessicles– Mitochondria

• Synaptic cleft– Primary– Secondary

invaginations• Muscle

– Post-synaptic density– Mitochondria

deHarven & Coers, 1959

By SEM

Sohn & al., 1999

Synaptic vessicle anchoring

• SV anchored by “pegs and ladders”

Harlow & al., 2000

Synaptic structure

• Complementary– Presynaptic active zone– Postsynaptic density/receptor

• ECM coordination– NerveagrinMuSK– MuscleLam 421/521VGCC

• Electrical coordination– Nerve: ubiquitinylation preserves synaptotagmin– Muscle: depolarization degrades AChR

Presynaptic side

• Docking site– SNAP-25– Syntaxin (T-SNARE)

• Synaptic vesicle– Synaptobrevin (V-SNARE)– Synaptotagmin

• Docking trimer: t/v-SNARE+SNAP• Calcium sensitivity: synaptotagmin

Presynaptic active zone

De Wit & al., 2009

Presynaptic active zone

Garner 2002

Postsynaptic side

• Post-synaptic density– MuSK/LRP4 receptor– Rapsyn/Dok-7 adapter– Src kinase– Acetylcholine receptor

• Junctional folds– Sodium channels– Acetylcholinesterase

Post-synaptic density

Shi & al., 2012

Afferent innervation

• Afferent– Sensory– Dorsal root ganglion– Synapses in SC

• Spindle– Muscle-like

cells– Mechanosensitive

nerve ending

Muscle Spindle

• Capsule• Polar regions

– -motorneurons– Striated contractile proteins

• Equatorial region– Primary afferent (Ia)– Secondary afferent (II)– Non-contractile– Nuclear bag & chain

Barker, 1948

Spindle afferents

Barker, 1948

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

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

Stretch responsePrimary ending

Houk & al, 1981

Secondary ending

Afferent firing rate

Muscle length

Ian Boyd video clip

Stretch Reflex

• Ia afferent“homonymous” motorneuron– Servo-like length control– Tendon tap– Vibration illusions

• IaIa interneuron– Inhibit antagonist(s)– Mechanical equivalence– Myotatic unit

• IIdorsal horn interneurons– Distributed, slower excitation

Golgi tendon organ

• Free nerve endings embedded in capsule at muscle-tendon interface

• Group Ib

Nitatori, 1988

Goldfinger & Fukami 1982

GTO response

• MTJ tension depolarizes afferent

Muscle length

Muscle force

GTO discharge rate

Crago & al., 1982

GTO Reflex

• IbIb interneuron– Delayed homonymous inhibition– Distributed excitation/inhibition– “Interaction” torques– Locomotor pattern integration

• Polysynaptic pathways are subject to extra modulation

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