Somatosensory System and Pain Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and...

Somatosensory Systemand Pain

Prof. Marshall Devor, Ph.D.Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life SciencesHebrew University of Jerusalem

lecture 3: The primary somatosensory neuron

פיסיולוגיה מורחב פיסיולוגיה מורחב 08-908-9

primary sensory neuron

from stimulus to impulse trainfrom stimulus to impulse train……varietyvariety

1. force transmission to sensory ending2. transduction3. spike encoding

primary sensory neuron

neural crest

neural crest

Primary sensory neurons are pseudounipolarPrimary sensory neurons are pseudounipolar

bipolar

pseudounipolar

growth cone

sensoryending

A

C

A

100 uM

CGRPCGRP peptide neurotransmitterpeptide neurotransmitter

RTRT9797 neurofilamentneurofilament

Theory of "target derivedTheory of "target derivedneurotrophism"neurotrophism"

Matsuda et al

no synaptic contacts in DRG

microvilli on DRG somata

• enlarged surface area• numerous neurotransmitter and other receptor types

primary sensory neurons

nociceptors

skin nerve muscle nerve m/sec A, A Ia, Ib, II 15-100+A III 2-15C (Remak bundle) IV 0.2-2

axonepineurialblood vessel

perineurium endoneurium

node ofRanvier

internode

paranode

1-2 mm

nodal gap2 um

Schwann cellsoma

Schwann cell (glia)

internode 1-2 mmnode of Ranvier 1-2 um

30 um

myelin formation

axon, myelin, Schwann cell, oligodendroglia

myelin formationmyelin formation

axon, myelin, Schwann cell

myelin formation in the CNSmyelin formation in the CNS

Schwann cell vs. oligodendroglial cell

node of Ranvier

contactin associated protein

adult: DRG neuron adult: DRG neuron phenotypephenotype depends dependson regulation of both on regulation of both expression expression andand traffic trafficof molecules ofof molecules ofexcitability (NTs)excitability (NTs)

A: LTMs: SA, RA, PC, hair A: warming, cooling, down hair, mechano-nociceptorsC: mechanical nociceptors mechano-heat nociceptors CMH polymodal nociceptors silent nociceptors

variety of primary afferent neurons variety of primary afferent neurons (stimulus encoding)(stimulus encoding)

“neuronal phenotype” (correlates of sensory receptor types)

response CV

m/sec

axon

diam.

myelin neurochem. periph.morph.

A LTM 15-100 3-15m heavy glutamate central morph.

A nociceptionthermal+LTM

2-15

1st pain

1-3 m light glutamate+

peptides

transductionchannels

C most

nocicept.

0.2-2

2nd pain

<1 m none glutamate+peptides (NGF)IB4 (GDNF)

electrogenicchannels

spike shape

TTX-STTX-R

neuro-filam.

channeldistrib.

somadiameter

surface receptors

DRG peptidesDRG peptides: SP, CGRP, NPY, NT, VIP, SOM, GAL, CCK… substance P, calcitonin gene related peptide….

“neuronal phenotype” (correlates of sensory receptor types)

response CV

m/sec

axon

diam.

myelin neurochem. periph.morph.

A LTM 15-100 3-15m heavy glutamate central morph.

A nociceptionthermal+LTM

2-15

1st pain

1-3 m light glut+

peptides

transductionchannels

C most

nocicept.

0.2-2

2nd pain

<1 m none glut+peptides (NGF)IB4 (GDNF)

electrogenicchannels

spike shape

TTX-STTX-R

neuro-filam.

channeldistrib.

somadiameter

surface receptors

DRG peptides: SP, CGRP, NPY, NT, VIP, SOM, GAL, CCK…

Somatosensory System and Pain

Prof. Marshall Devor, Ph.D.Dept. of Cell & Animal Biology and Center for Research on Pain Institute of Life SciencesHebrew University of Jerusalem

lecture 3: The primary sensory neuron

פיסיולוגיה מורחבפיסיולוגיה מורחב

spike invasion and the safety of through-conduction in DRG neurons …. why are DRG neurons excitable ?

NEURONsimulation

spike invasion

Conclusion: spike invasion is a design feature ofDRG neurons… but to what end ??

somatic

through-conduction