II. Neocortex: The role of the neocortex is
to store and manipulate memories
1. Frontal lobe: encodes
and manipulates action
memories.
Frontal
lobe
2. Dorsal cortex (occipital, parietal,
and temporal lobes): stores
encoded sensory memories.
Parietal
lobe
Temporal
lobe
Occipital
lobe
1. Frontal lobe: encodes and
manipulates action memories
Dorsal
Ventral
or crossover
• A single skeletal muscle cell is
called muscle fiber (MF)
– electrically continuous inside,
– electrically isolated from outside
• Each MF is formed during
development by the fusion of a
number of undifferentiated
mononucleated cells, known as
myoblasts
• Myoblasts fuse into multinucleated
cylindrical MF; completed by
around the time of birth
One
=
cell
• Single MF is 10µm to
300µm in diameter and
may extend up to 30cm in
length (whole length of
biceps muscle) and
contain >1,000 nuclei
• DEFINITION: muscle is a
number of MFs bound
together by connective
tissue (collagen)
• Muscles are connected to
bones by tendons (triple
helix of protein collagen*
- stronger than steel of
the same diameter)
• Tendons can be very long:
some of the muscles that
move fingers are located
in the forearm**.
• Why finger muscles are
away from the hand?
• What is the relationship between a motor neuron and
muscle fibers?
A.
B.
C.
D.
one motor neuron innervates one muscle fiber
several motor neurons innervate one muscle fiber
one motor neuron innervates two or three muscle fibers
one motor neuron innervates around 100 muscle fibers
• Definition: Motor
unit = motor neuron
and MFs it controls
(usually several
hundred MFs)
Ventral root
• Motor unit 1 = motor
neuron 1 and blue MFs
• Motor unit 2 = motor
neuron 2 and red MFs
• The muscle
fibers of a
motor unit are
dispersed
randomly
within the area
of the muscle
• Muscle fibers
innervated by
the same
motor neuron
are not
contiguous
The number of motor units vary
greatly among muscles:
• 10 in extraocular muscles
• 100 in intrinsic muscles of the hand
• 5,000 in a large leg muscle
The number of muscle fibers
(cells) per muscle:
• 1000 MFs in extraocular
muscles
(1000 MF / 10 motor units
 100 MF in one motor
unit)
• 1,000,000 MF in large leg
muscle
(1,000,000 MFs / 5,000
motor units  200 MFs in
one motor unit)
The strength of muscle
contraction depends on:
1. The number of motor units recruited
2. The frequency of motor unit discharge
3. The speed of contraction of muscle fibers in
the motor unit
4. The nature of motor unit (whether it is
fatigue-resistant or fatigue –prone)
Contraction duration:
• Snail muscle  contraction can last for 1
second
• Honey bee  contraction lasts for 3
millisecond (300 twitches / second)
In all skeletal muscles:
• Contractile elements: Actin, myosin
• ATP provides energy
• Increase in calcium concentration triggers
contraction
Single cell (electrically
isolated)
Sarcomere
2um
1um
• Sarcomere (Greek: sarco- (“flesh”) + -mere (“component”))
• Sarcomere shortens during contraction like a collapsing
telescope
• Stack many sarcomeres together longitudinally  myofibril
• A single myofibril has the length of a muscle fiber
• Muscle fibers look striated
under the light microscope
Inside a sarcomere
Myosin cross-bridges are pulling on the actin
Actin is
attached
to Z-line
discs
Z-line disc
Actin is
attached
to Z-line
discs
Actin= thin filament
Myosin is
suspended
by titin
titin
Myosin = thick filament
•
three sarcomeres stuck longitudinally
• sarcomere
cross section
Range of sarcomere contraction
Cannot contract
any further 
No tension
Range of sarcomere contraction
Cannot form crossbridges No tension
Actin is found in a any cell
actin
Fibroblast labeled with probes for
actin and the nucleus. The actin of
cytoskeleton is visualized
Tropomyosin is held in
place by Troponin
• Myosin tails bind
to form the
Calciumtogether
binding
protein
thick filament
Myosin head
120nm
• Myosin head interacts
with actin
• Hydrolyzes ATP
Cross-bridge cycle in 5 frames
1. Actin (A) bound to myosin (M):
A· M
2. Binding of ATP dissociates
myosin:
A· M + ATP  A + M· ATP
fast reaction
3. ATP hydrolysis to ADP and Pi
energizes myosin:
A + M· ATP  A + M · ADP · Pi
fast reaction
4. Cross-bridge binds to actin, now
ADP and Pi can be released:
A + M · ADP · Pi A · M · ADP · Pi
5. As soon as ADP + Pi are released,
the head region is glad to bend back
and pulls actin filaments:
A · M · ADP · Pi A · M + ADP + Pi
1. Actin (A) bound to myosin (M):
A· M
Muscle is stiff. Few hour after
death no ATP  Rigor mortis
(Lat. Stiff death)
2. Binding of ATP dissociates
myosin:
A· M + ATP  A + M· ATP
Muscle is flexible
3. ATP hydrolysis to ADP and Pi
energizes myosin:
A + M· ATP  A + M · ADP · Pi
this myosin head position is unstable. It wants
to bend back, but it cannot until it releases
ADP and Pi. Without binding to actin, myosin
releases ADP and Pi very slowly: half life is 14
seconds  Even at rest muscle continues to
burn ATPs  producing heat
4. Cross-bridge binds to actin
5. As soon as ADP + Pi
are released, the head region is
glad to bend back and pulls actin
Two distinct roles of ATP in crossbridge cycle
1. The energy released by ATP hydrolysis
provides the energy for cross-bridge
movement.
2. The binding of ATP to myosin allows myosin
to dissociate from actin
– Several hours after death ATP concentration
decreases  skeletal muscle become stiff (Rigor
mortis)
– The stiffness disappears in 48h to 60h after death
as a result of disintegration of muscle tissue
• Only 50% of cross-bridges are bound at any moment
• One stroke of cross-bridge produces only a very small
movement (~10nm)
• As long as muscle remains ‘on’ cross-bridges repeat their
swiveling motion
• What keeps muscle from continuous contractile activity?
What keeps muscle from continuous contractile activity?
Tropomyosin is held by
Troponin in resting
muscle in the position
that does not allow
myosin to bind to actin
33
Muscle tension
100nM
1µM
Calcium concentration
10µM
• Muscle tension is a function calcium concentration
+30mV
1. Motor neuron
action potential
Excitation-contraction coupling
-80mV
+30mV
-90mV
EPSP
2. EPSP is amplified
 Muscle fiber
action potential
Depolarization produced by influx
of Na (through ACh channels) is
amplified by muscle’s own voltageactivated channels
4. Calcium
concentration
inside
5. Muscle tension
(one twitch)
3. Muscle fiber action potential is
conducted from neuromuscular junction
located in the middle of a fiber to both
ends of a muscle fiber
• Where does calcium
come from?
Where does calcium come from
in a neuron?
• From ECF.
• Since concentration gradient is huge (1mM outside vs. 0.0001mM
inside), it is enough to just open calcium channels
 calcium will be pouring into the axonal terminal
• It works for axon terminals, since axon terminals are small (1µm)
• muscle fibers on the other hand are huge (up to 300µm)
 it would take forever for calcium from ECF to diffuse to central myofibrils
Solution surround each myofibril with calcium storage
• AP opens calcium channels on SR
• After the end of AP, calcium is sucked away by a
number of ATP driven pumps: 30,000 pumps/ µm2
How to transmit AP to all s. reticula simultaneously?
Solution T-tubules (local plumbing) - electrically continuous with ECF,
just like power lines in a house are used to transmit electricity
Temporal summation and Tetanus
isometric
contraction ==
constant length
•
Maximum tension that
this muscle can produce
under this length
• In a lab we
can
manipulate
muscle length
 measure
maximum
tension
developed by
the muscle at
that length
isometric contraction ==
constant length
• Conclusion: there is some
optimal length at which the
developed tension is maximal
• mechanism? - consider myosin and actin arrangement:
isometric contraction ==
constant length
• In the body muscles are close to optimal length (a) in the extended state.
• Bones prevent muscles from extending beyond this length
isometric contraction ==
• How much muscle will shorten with the
weight of 50 gram
• With a load of 50gram this muscle will
only shorten to E
• each sarcomere will shorten by 0.5µm
(from 2.1µm to 1.6µm)
50 gram
50 gram
(gram)
isotonic contraction == constant load
E
Types of skeletal muscles
Two types of tasks:
– Some tasks involve continuous muscle activity
(tonus, walking)  muscles are not allowed to fatigue.
Movements involved in these tasks are usually slow.
– Other tasks normally last only short time
(running away from a predator). The movements
involved in these tasks are usually fast.
To address these two very different tasks, we have two
different types of muscles fibers:
– slow MF that are optimized to never fatigue: you can walk for
2 miles (using slow muscles) without getting tired
– fast MF that are optimized for speed, but fatigue quickly: if
you run two miles (using fast muscles, you will be very tired)
Contraction velocity
Slow (Type I)
twitch
waveform
Fast (Type IIx)
30ms
300ms
Rate of fatigue
never
quickly
Why fast/slow?
Myosin ATPase activity is slow (slowly split ATP)
Myosin ATPase activity is fast (split ATP fast)
Source of ATP production
Oxidative phosphorylation (aerobic)
Glycolysis (anaerobic)
Mitochondria
Many
Few
Myoglobin content
High (red muscle)
Low (white muscle)
Fiber diameter
small
large
Motor unit size
small
large
Capillaries around MF
Large number of capillaries
Few capillaries
Motor unit firing rate
Continuously at a low rate
High firing rate
Athletes
Extreme endurance athletes
World-class sprinter
Tension
fine control by
slow MF
gross control by
fast MF
time
Find the slow-twitch MF, fast?
fast MF
(big and
white)
slow MF
(small and
red)
Sensors
• Close your eyes move
your hand forward,
back
• How do you know the
position of the
muscles?
• Two types of sensors:
• Length sensors inside
the muscle: muscle
spindle
• Tension sensors: Golgi
tension organ
Golgi tendon
organ
• How sensory information is encoded by neurons?
• Information is encoded in frequency of action
potentials (firing frequency = number of action
potentials per second)
• How motor information is encoded by a motor neuron?
• Again, information is encoded in frequency of action potentials:
the greater the firing rate  the greater the tension
• What is the range of firing rate?
• Is every motor neuron action potential followed by a muscle
contraction?
• In addition CNS can recruit more motor units
Amyotrophic lateral sclerosis
• Also known as Charcot disease, Lou Gehrig's
disease in US and motor neuron disease in UK.
• Lou Gehrig (1903 – 1941) was a baseball player
who played 17 for the New York Yankees, from
1923 through 1939. In 1939 he was diagnosed
with ALS and died two years later.
• ALS is characterized by gradually worsening
muscle weakness. This results in difficulty
speaking, swallowing, and eventually breathing.
• The defining feature of ALS is the death of both
upper and lower motor neurons in the motor
cortex of the brain, the brain stem, and the
spinal cord. Prior to their destruction, motor
neurons develop protein-rich inclusions in their
cell bodies and axons.
• In 90% of case the cause is unknown. In 10%
ALS is due to inherited mutation.
• Stop here