Transcript Neural and Sensory - Georgia Institute of Technology

Neural and Sensory
• Efferent innervation
– Neuromuscular junction
– a-, g-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
Dorsal/posterior
– 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
Ventral/anterior
MN
density
Cervical
Arm/hand
Thoracic
• 10,000+ inputs per MN
Lumbar
• Excitatory glutamic synapses
Sacral
• Inhibitory glycinergic/GABAergic synapses
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
– NerveagrinMuSK
– MuscleLam 421/521VGCC
• 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
– g-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 response
Primary ending
Secondary ending
Muscle length
Afferent firing rate
Houk & al, 1981
Ian Boyd video clip
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
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
GTO discharge rate
Muscle force
Crago & al., 1982
GTO Reflex
• IbIb interneuron
– Delayed homonymous inhibition
– Distributed excitation/inhibition
– “Interaction” torques
– Locomotor pattern integration
• Polysynaptic pathways are subject to extra
modulation
Summary
• a-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