Neuromuscular

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PERIPHERAL AXONS: CHARACTERISTICS

Axons
  Caliber
  Conduction velocity
  Motor unit action potentials
  Myelin
  Transport
  Unmyelinated
Cutaneous afferents
Dorsal root ganglia
Mechanotransduction
Motor
Muscle spindle
Muscle & tendon afferents
Nociceptors
Thermoreceptors
  Temperature-sensitive channels

External link
  Nerve impulse

Mills

Sensory Axon types


Sensory Axons

CUTANEOUS SENSORY AFFERENT AXONS
Mechanoreceptors: Low Threshold 13
Light touch
  Mechanosensitive channel: PIEZO2
  Indentation forces for activation: As low as 0.5 mN
Name Stimulus Type Skin End Organ Axon Class Sensation Molecular Factor
Survival Functional
Glabrous (Hairless) Skin
Rapid
  adapting
Displacement
  velocity
Meissner Corpuscle
  Dermal papillae apex
Aαβ
  TrkB+: Rapid adapt
  Ret+: Slower adapt
  26–91 m/s
  Receptive field
    Intermediate
Vibration
  40 to 60 Hz
Tapping
? USH2A
S100
  Lamellar cells
Pacinian
  corpuscle

Rapid adapt
Displacement
  transient
Pacinian Corpuscle
  Dermis, Deep
  Glabrous & Hairy
    Skin
Aαβ
  Ret+
  26–91 m/s
Vibration
  100 to 400 Hz
Buzz; Flutter
? S100
  Lamellar cells
Slow
  adapting
    (SA) 1
Displacement Merkel cell-Neurite
  Rete ridge
  Glabrous & Hairy
    Skin
Aαβ
  TrkC
  16–96 m/s
  Receptive field
    Small
Sustained
  pressure
    (Indentation)
Vibration
Shape; Texture
Light touch
NT3 BDNF
PIEZO2
Marker: Atoh1
Slow
  adapting
    (SA) 2
Displacement Ruffini
  Dermis
Aαβ
  20–100 m/s
Stretch >
  Indentation
? ?
Hairy Skin
Field Displacement
  velocity
Hair follicles
  Awl/auchene
  zigzag
  Guard
Nerve Ending
  Circumferential
Aαβ
  TrkC+/Ret+
  15-25 m/s
  Receptive field
    Large
Skin stroke ? ?
D hair Displacement
  velocity
Lowest
  mechanothreshold
Hair follicles
  Awl/auchene
  zigzag
Nerve Ending
  Longitudinal
    Lanceolate

  TrkB
  5-30 m/s
  Receptive field
    Intermediate
Hair deflection
  Direction-
    selective
Skin stroke
Indentation
NT4; NT3
via TrkB
± p75; ?NT4
T-Ca++ channel
  (Cav3.2) 2
C tactile Light touch
  Low threshold
Lanceolate C
  TH+
  0.2-2 m/s
  Receptive field
    Intermediate
Hair deflection
Skin stroke
Indentation
? VGLUT3
Rapidly
  Adapting
Displacement
  transient
Hair follicle
  Guard
  awl/auchene
Nerve ending
  Longitudinal
    Lanceolate
Aαβ
  26-91 m/s
Hair deflection
Skin stroke
Indentation
? ASIC-2 Na+
  channel
Mechanoreceptors: Other
High
  Threshold
Displacement Hair follicles
  Epidermis
  Guard
  awl/auchene
  zigzag
Nerve ending
  Free
  Circumferential
Aαβ, Aδ, C
  0.5-100 m/s
High force
  Indentation
  Hair pull
? ?
Thermoreceptors 10
Name Stimulus Type End Organ Class Sensation Trophic Factor
Survival Functional
Cold Cooling
Menthol
Unmyelinated
  neurite complex

C
Cool
  Innocuous
? ?
Cold
  Allodynia
Cooling ? Large
  Neurons
Pain ? ?
Warm Warming
  Slow adapting
  Fast adapting
? C Warm
  Innocuous
? ?
Also see
  Temperature-sensitive channels
  Noxious temperature
Nociceptors
Name Stimulus Type End Organ Class Sensation Trophic Factor
Survival Functional
Myelinated
Pain Unmyelinated
  Neurite-Schwann
  cell complex
Basal epidermis
Myelinated axons
Aαβ
Pain
  Sharp
  Stinging
NGF p75; NGF
C Inflammation
  Hyperalgesia
Not responsive to
  mechanical &
    heat pain
Unmyelinated
  axons
Project to spinal
  Lamina I &
  Lamina IIouter
CMi Pain
  Dull or
  Sharp Burn
NGF
trkA
p75; NGF;
trkA; CGRP;
Substance P &
  NK1 receptor
Nerve injury
  Hyperalgesia
Responsive to
  mechanical &
    heat pain
Unmyelinated
  axons
Project to spinal
  Lamina IIinner
Noxious heat: TRP-V1
CM Pain
  Dull or
  Sharp Burn
NGF
trkA
GDNF; Ret
GFRα;
FRAP & TMP;
P2X3 ATP
  Receptor
Heat
Cold
Unmyelinated
  axons
C Temperature
  hypersensitive
? mTORC1
Itch
Histamine
Unmyelinated
  axons
Project to spinal
  Lamina I
C Itch trkA ?

Muscle Axons

MUSCLE & TENDON AFFERENT AXONS: Proprioception
Name Stimulus
Type
Afferent
End Organ
Efferent
Termination
Effect Class Trophic
Factor
1° sensory Muscle stretch
  Phasic
Spindle
Intrafusil fibers
  Nuclear region
  DB1; 1 branch
  SB2 & chain;
    2nd branch
Motor
Neuron
Excite
  homonymous muscle
Monosynaptic reflex
Ia NT3
2° sensory Muscle stretch
  Tonic
Spindle
Nuclear chain fibers
  ± SB2
Motor
Neuron
Excite
  homonymous muscle
Mono & Polysynaptic
II .
Golgi tendon Tendon stretch
  Phasic &
  Sustained
Myotendinous junction
Golgi tendon organ
  Inhibit
  homonymous muscle
Ib .
Proprioception 8
Axon Current stimulus: Mechanical activation (MA); Muscle stretch
Axon Current type: Rapidly adapting
Neuron currents
  Ion: Na+ > > Ca++
  Channel: Piezo2
    Location: Muscle spindle & Golgi tendon organ sensory endings
    Function: Mechanotransduction
Afferent neuron molecular marker: Parvalbumin



MUSCLE SPINDLES

Disorders
General
Histology
Innervation
  Afferent
  Efferent

Spindles 7
MUSCLE SPINDLE INNERVATION (simplified)

From: University of Glasgow
Muscle Spindle Afferents
  • Axon size: IA
  • Express α3 isoform of Na+/K+-ATPase


MOTOR EFFERENT AXONS
Name Low frequency
stimulus effect
Muscle Fibers Innervated Ending type Class Trophic
Factor
Dynamic γ Minor contraction
Increased stretch response
Spindle (Intrafusil)
  Dynamic Bag1 (DB1)
Indented plate
at poles of fibers
II NT3
Static γ Smooth contraction (SB2) Spindle (Intrafusil)
  Static Bag2 (SB2)
Indented plate II NT3
Oscillation Spindle (Intrafusil)
  Chain
Trail
Dynamic β ? Extrafusil
Intrafusil: DB1
Compact (p1) endplate . .
Static β ? Extrafusil
Intrafusil: Chain
Compact (p1) endplate . .
α Muscle fiber contraction Extrafusil Compact (p1) endplate I .

Muscle Spindles: Normal

Spindle images: Other
  AChE deficiency
  Fetal
  Focal myositis
  Phosphorylase deficiency
  SMA-LED

Spindle with Intrafusil Muscle Fibers & associated Axons

Gomori trichrome stain

Muscle Spindle: Fiber Innervation (Rodent)

Silver stain

Perimysial Structures
Spindle
Intramuscular nerve
Vessels
    Vein
    Artery

VvG stain

Muscle spindle with esterase-stained neuromuscular junctions

Esterase stain

Muscle Spindle
Coarse internal architecture similar to regenerating or immature extrafusil muscle fibers

NADH stain


Babinski 1889

Muscle Spindle Disorders


Axon: Caliber


Axon: Conduction Velocity


Axon: Transport 4

Disorders
General substrates
Types
  Anterograde
  Retrograde
  Synaptic regions

Motor Unit Action Potentials (MUAP)


Dorsal Root Ganglion

Dorsal Root Ganglion (DRG) Development: Cell origins DRG anatomy DRG Neurochemistry DRG Sensory modalities: Neurophysiology & Anatomy
Also see
  Sensory Neuronopathies
  Sensory Ataxia

Temperature Sensing Channels 3

Ion channel Activating temperature Activators
VRL-1 (TRPV2) 53 °C Noxious heat
VR1 (TRPV1) 45 °C Noxious heat
Capsaicin
pH < 5.9
Vanilloids
Endocannabinoids
TRPV3/TRPV4 (VRL-2) 30 to 40 °C Warm
TRPM3
TRPV1
TRPA1
> 41 °C Noxious heat
CMR1/TRPM8 < 25 °C Cold
Menthol
TRPA1 (ANKTM1) < 17 °C Noxious cold
Icilin
See



Mechanotransduction Channels 5


Remak: 1st description of non-myelinated fibers (axons) 9


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Return to Molecular Classifications

References
1. Nature Neurosci 2002;5:254-260
2. Nature Neurosci 2003;July
3. Gut 2003;52:1233–1235
4. Neuron 2010;68:610-638, Nat Rev Neurol 2019 Sep 26, J Neuromuscul Dis 2019 Sep 20
5. TINS 2012; Online May 21
6. Neuron 2012;74:961-963, Neuron 2012;74:1015-1022
7. Pflugers Arch 2014 Jun 3, Skelet Muscle 2021;11(1):3
8. Nat Neurosci 2015;18:1756-1762
9. Remak 1838
10. Handb Clin Neurol 2018;156:47-56
11. Acta Neuropathol 1996;92:597-602
12. Curr Opin Neurobiol 2020;63:87-94
13. Nat Rev Neurosci 2021 Jul 26

7/15/2021