The Skin: Largest Organ in the Body

The

Ski

n: L

arge

st O

rgan

in th

e B

ody

Distortion due to variation in the size and density of sensory

neuron ‘receptive fields’

The Stimuli of Somatosensation

SKIN (body surface)– Mechanical pressure: this is ‘touch’– Vibration (Hz): this is generally ‘texture’– Damage/Temp (pain/hot/warm/cold)– Chemical (example is menthol)

MUSCLES &TENDONS (body position)– Stretch, Tension– Kinesthesis, Proprioception

BODY SURFACE + BODY POSITION = “HAPTIC PERCEPTION”

Rec

epto

rs c

an b

e ch

arac

teri

zed

in te

rms

of:

1.S

tim

ulat

ion

Type

(pre

ssur

e, v

ibra

tion

, tem

p, d

amag

e)

2.S

ize

of R

ecep

tive

Fie

ld (a

mou

nt o

f br

anch

ing)

3.R

ate

of A

dapt

atio

n (s

low

, med

ium

, fas

t)

Basket Cell

Pacinian corpuscle

Free Nerve Endings

Pacinian CorpusclesDetect Vibration (texture)

PressureStimulus

PacinianActivity

Mus

cle

Spi

ndle

– S

tret

ch R

ecep

tor

Gol

gi T

endo

n O

rgan

– T

ensi

on R

ecep

tor

Rec

epto

rs i

n M

usc

les

and

Ten

do

ns

En

cod

e B

od

y P

osi

tio

n

Mus

cle

fibe

r

Red

is m

otor

Blu

e is

sen

sory

Sens

ory

fibe

rat

tach

ed t

o te

ndon

Bone

Muscle

This is a Muscle spindle, but other Mechanoreceptors (i.e., Basket Cells and Pacinian Corpuscles) also work this way

The cytoskeletal strands are like the ‘tip links’ of inner hair cells.

Ion channels ‘pulled open’ by

mechanical force.

Skin Senses: 2 Pathways to Cortex

Lemniscal Pathway (mechanorecepetors)

– Tactile, pressure, Basket Cell (detect)– Tactile, vibration/texture, Pacinian Corpuscle (ID)

Spinothalamic Pathway (free nerve endings) – Tissue Damage, pain, Nociceptor (detect)– Temperature, hot/cold, Thermal Receptor (ID)– This pathway is ‘gated’ in the spinal cord

D o r s a l – S e n s o r y

V e n t r a l – M o t o rHypothalamus

Thalamus

Spinal Cord

Thalamus

Cortexparietal

Hindbrain

Dorsal

Ventral

Thinking in 3D• Dorsal/Ventral Organization• Left/Right Crossing

Cortexfrontal

DORSAL

SENSORY NEURONSMUSCLES

MUSCLES

Som

atot

opic

Org

aniz

atio

n

2D ReceptorArray

Thalamus

Primary Cortex

However…

Dense 2D Receptor Array

Thalamus

Cortex Is‘Modular’

Means the size and density of cortical columns is fixed

Lemniscal System(mechanoreceptors)

Spinal Cord

Thalamus

Cortexparietal

Hindbrain

Cortexfrontal

PACINIANCORPUSCLE

Fuzzy

Receptive fieldsperiphery vs. cortex

Stimulation anywhere within this large receptive field goes to one cortical column Stimulation

within this tiny receptive field goes to one cortical column

Two-Point DiscriminationConverging neurons = Less discrimination,Lower threshold

Less convergence= More discrimination,Higher threshold

Detect Identify

Sensory(parietal)

Motor(frontal)

The brain has no ‘sense’ of itself

Two-

Poi

nt T

hres

hold

sWhere best for Braille?

Pressure(Detect)

Two-Point(ID)

Thresholds for Detection and Identification

Receptive fieldsperiphery vs. cortex

MonkeyCortex

Experience Changes Cortical Maps

what happens if you lose a finger? cortical maps will readjust experience alone can readjust - the

example of violin training - young vs. old

What is the result of all this ‘experience’?

Smart? Dumb? Dumber?

Variation in Cortical MapsOverall brain weight differs by ~30%

Size of primary cortical areasdiffers by as much as 100%

Touch Vision Audition

Blind

Normal C

ortex is allocated based on useT

he beauty of modular architecture

“Colum

ns is Colum

ns”

Nociceptors respond to AND release chemical stimuli(the basis of inflammation)

Pain Is A Perception:The Stimulus is Tissue Damage

PainPainPainPain

Convergent Excitation: lower thresholds (better detection) come at a cost of lousy ID.

Heart Attack? Lung Pain? Arm Pain?

Spi

nal G

ate

The

ory:

Two

Way

s to

Inh

ibit

L-fibers are mechanoreceptors

S-fibers are free nerve endings

1.

2.

Spinothalamic System(free nerve endings)

1. Nociceptor (excitatory)

3. Modulatory Brainstem neurons (excitatory)

Spinal Cord

Thalamus

Cortexparietal

Hindbrain

Cortexfrontal

Opiate Neuron (inhibitory)

2. Mechanoreceptors (excitatory)

2.

3.

1.

OUCH!

Spinothalamic System(free nerve endings)

1. Nociceptor (excitatory)

3. Modulatory Brainstem neurons (excitatory)

Spinal Cord

Thalamus

Cortexparietal

Hindbrain

Cortexfrontal

Opiate Neuron (inhibitory)

2. Mechanoreceptors (excitatory)

2.

3.

1.

Spinothalamic System(free nerve endings)

1. Nociceptor (excitatory)

3. Modulatory Brainstem neurons (excitatory)

Spinal Cord

Thalamus

Cortexparietal

Hindbrain

Cortexfrontal

Opiate Neuron (inhibitory)

2. Mechanoreceptors (excitatory)

2.

3.

1.

Hindbrain(5-HT, NE)

Midbrain(DA)

Dopamine (DA)Serotonin (5-HT)Norepinephrine (NE)

“one-to-many”

Architecture of‘Modulatory’ Systems

Endogenous Opiates

Common practice to name neurotransmitters after the plant-derived chemical that mimics their action in the brain

Morphine-like neurotransmitters Endorphins, Enkephalins Role in suppressing pain (i.e., inhibiting input

from nociceptors) Opiate neurons found throughout brain and

spinal cord – not all are involved in pain

EPSP: glutamate IPSP: gaba or endogenous opiate

Synaptic potentials are brief (a few milliseconds) positive or negative changes in voltage.Occur at dendrites – positive and negative summate.

Caused by neurotransmitter released from a presynaptic neuron.EPSPs increase likelihood of action potentials, IPSPs decrease that likelihood.

+

-YES! NO!

Drug effect: excitatory agonist

Drug effect: inhibitory agonist

Agonist drugs can also produce positive or negative changes in voltage.They do so by mimicking the chemical structure of naturally-occurring neurotransmitters.

However, the DURATION of their effects can be minutes or hours.Neurons respond to this stimulation by making themselves more or less excitable.

Leads to dose tolerance and with persistent use, chemical dependence.

YEEEEEEEEEEEEEEEEEEEEEEEEEEEEEESSSSSSSSSSSSSSSSSSSSSSSSSS!

NOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO!

Sho

rt te

rm e

ffec

t of

mor

phin

e is

incr

ease

in K

+ c

urre

ntL

ong

term

eff

ect o

f m

orph

ine

is in

crea

se in

Na+

cur

rent

Why

dru

gs p

rodu

ce c

hem

ical

dep

ende

nce.

. .

. . .

even

‘go

od’ o

nes

The ‘Spinal Gate’ in actionCell bodies inbrainstem

dorsal

ventral

Activation of a Nociceptor

Activation of a Nociceptor: Inhibition by Enkephalin / Morphine

Cone Snail Venom

Venom consists of a‘cocktail’ of proteins

One of these venomproteins blocks ‘N’type calcium channels

Nociceptors have ‘N’type calcium channelson their axon terminals

Neurotransmitters

Ca++ K+ Na+

Where a venom (or drug) could work. . .

Receptor Agonists / AntagonistsReuptake Inhibitors