Download MOTOR SYSTEM PHYSIOLOGY

MOTOR SYSTEM PHYSIOLOGY
April 6 and 7, 1998
D. Michele Basso, Asst. Prof.
Office Hrs. by Appointment; 2-0754;
[email protected]
Reading Assignment:
Kandel, Schwartz, Jessell "Principles of Neural Science" 3rd edition. Chapters
36, 37, 38.
Book is on closed reserve at the library. **figure taken from Kandel, chwartz,
Jessell 3rd edition Objectives: Students will be able to:
to
1. Identify ultrastructural components of muscle and describe their relationship
muscle contraction, force development and movement.
2. Classify each type of motor unit and discuss how motor unit recruitment is
modulated to meet the demands of the movement and/or task.
3. Identify all components of the muscle spindle and golgi tendon organ and
discuss: the range of sensitivity for both structures; the relationship between
sensitivity and muscle tone; and, the CNS mechanisms that modulate muscle tone.
4. Describe the role of the muscle spindle in producing simple and complex
movements.
5. Classify the different types of interneurons and describe their roles in
modulating movement.
6. Describe the structure, organization and interaction of spinal cord systems
which
produce
simple,
complex
and
locomotor
movements.
SAMPLE QUESTIONS
Students: I have prepared a few tips and questions to help you prepare for the
exam. Listed below are several questions. Once you have answered them, you can
check your answers to some I thought up. Note that many of these questions do not
have
ONE,
Single
correct
answer.
If
you
have
difficulty
understanding the logic behind my answers, please drop me an email with
your question and I'll respond within 24 hrs.
[email protected]
Tips on preparing for motor system physiology portion of the exam:
1. Integrate the material, be prepared to describe movement in terms of its underlying
details such as changes in the muscle spindle, gamma biasing, muscle mechanics.
Remember we started off the lecture series with the question
"How do we move?"
2. Some things to think about:
a. What movements utilize greater dynamic than static
b. What movements use greater static than dynamic
c. What conditions rely primarily on primary spindle
d. What conditions rely primarily on secondary spindle
e. What would the firing rate of the spindle afferents, both primary
during the following activities:
-
gamma biasing?
gamma biasing?
afferent firing?
afferent firing?
and secondary, be
Sleeping on a moving subway train:
Standing to deliver a speech:
riding a horse:
f. Does spasticity affect the amount of actin-myosin overlap at rest?
How is a movement successfully executed?
Muscle Ultrastructure
1. The basic contractile element of muscle is the sarcomere
a. The sarcomere is made up of overlapping thick and thin filaments
b. Thick filaments are made up of ~200 myosin molecules
c. Each molecule has a double helix tail of heavy chain polypeptides and two globular
protein heads
d. Thin Filament is comprised of an actin backbone wound in a helix
with tropomyosin proteins. Troponin molecules are located on ach tropomyosin
protein.
Muscle Contraction
1.
Each muscle fiber contains hundreds to thousands of sarcomeres. Within
the sarcomere, the myosin filament lies between the thin actin filaments.
2.
Muscles contract by a process called excitation-contraction coupling
which causes the actin filaments to slide over the myosin filaments.
First: An action potential from the motor neuron causes a release of Ca++ into the
intracellular space of the muscle fiber.
Second: The Ca++ binds to troponin and, through mechanisms not fully understood,
produces a conformational change in the actin filament therby exposing active
binding sites.
Third: The myosin heads bindto these active sites forming a cross-bridge between
actin and myosin filaments.
Fourth: Binding of myosin heads to actin continues down the length of the filament
which rotates the head of the myosin and slides the actin across the myosin.
Fifth: This process will continue as long as ATP, Ca++ and active binding sites on
actin are available.
Movement is the result of force development and muscle contraction.
affecting contraction force include:
Factors
a. Initial length of the muscle
b. Velocity of length change
c. External loads opposing the muscle
MNs are topographically organized
1. In the horizontal plane the motor neurons controlling proximal muscles
are located medially and those controlling muscles of the digits are
found laterally
2. MNs are also organized longitudinally in muscle specific groups call
motor neuron pools.
3. Mediolateral position in the horizontal plane indicative of distal
musculature
4. Muscle Contraction is the direct result of firing of the alpha motor neurons
in the ventral horn of the spinal cord.
1. A single ? motor neuron supplies many muscle fibers and is called a motor
unit.
2. Each muscle fiber is innervated by only 1 motor neuron
3. The number of fibers innervated by a single motor neuron varies according
to the size and precision of the muscle. This is the innervation ratio.
a. Precise Motor Control: Extraocular muscles have an innervation
ratio of 1:10
b. Intermediate Motor Control: Intrinsic muscles of the hand have
an innervation ratio of 1:200
c. Gross Motor Control: Leg muscles (gastrocnemius) have
an innervation ratios of at least 1:2000
Classification of Motor Units
1. There are at least 3 types of motor units based on physiological and
anatomical parameters:
Slow Oxidative
Fast Fatigue Resistant
Fast Fatiguable
Metabolism
Aerobic, oxidative Anaerobic, oxidative and Anaerobic, glycolytic
enzymes
glycolytic enzymes
enzymes
Contraction
Force
Low
Intermediate
High
Contraction
Velocity
Slow
Fast
Fast
Motor Function
Postural
Control,
Intermediate Endurance
Endurance
Rapid,
Powerful
Movements
Fiber Type
Type I
Type IIB
Type IIA
Motor Unit Recruitment
1. Motor Units are recruited in a fixed order according to the size of the motor
neuron and the force generating capacity of the motor unit.
2. Orderly recruitment was first described based on the size of the motor neuron.
The surface area of the cell is inversely related to its input resistance. Thus,
smaller neurons have higher input resistance and are more likely to fire given that:
V (action potential) = I (current) x R (resistance)
Therefore, if a small and large MN receive the same synaptic drive or current, the
small MN will reach threshold and fire before the large MN because of its greater
input resistance.
3. Recruitment is also related to motor unit force. Motor neurons
demonstrate intrinsic differences in excitability which are related to contraction force of
the muscle fibers. Cells with high levels of excitability produce low twitch tension
values during muscle contraction.
4. Thus, the nervous system uses stereotypic recruitment of motor units to meet
the demands of the task. The weakest motor units are recruited first and as
synaptic input increases, progressively stronger motor units are recruited.
In this way, a continuing rise in muscular force is ensured and smooth gradations in
force result in smooth, yet powerful movements.
Rate Modulation
1. Muscle force can be increased by increasing the firing frequency of the motor
neuron.
2. A single action potential causes a twitch of the muscle fiber which dissipates
rapidly.
When the firing rate increases, multiple action potentials bombard the muscle
fiber before the force has completely dissipated.
3. The series of muscle twitches will summate, and the force will ramp up so that
a greater level of force is attained. This is referred to as Temporal Summation.
4. Once the firing rate reaches a high enough level ~30 hz the muscle fiber
force production rapidly increases to high levels and maintains this level of force.
The individual action potentials result in small fluctuations in force. This is known as
unfused tetanus.
5. Temporal summation and unfused tetanus are used under normal conditions
to produce force. In experimental settings, the muscle nerve can be stimulated
much faster than the physiological firing rate of the MN. In this condition, maximal
force is produced by the muscle and there is no opportunity for relaxation in the
fibers.
This is called fused tetanus.
Monitoring the State of the Muscle
1. The CNS receives information about the state of the muscle from two receptors
within the muscle itself.
2. The muscle spindle provides information about the length of the muscle.
3. The Golgi Tendon Organ signals changes in muscle tension.
**
The Muscle Spindle
1. Muscle spindles are distributed throughout the fleshy part of the muscle and
run parallel to the individual muscle fibers.
2. Each encapsulated spindle contains:
a. A group of small specialized muscle fibers called intrafusal fibers
b. Sensory or Afferent axons
c. Motor or Efferent axons
3. The intrafusal fibers do not contribute to force production which distinguishes
them from skeletal muscle fibers called extrafusal fibers.
a. Intrafusal fibers include Static and Dynamic Nuclear Bag fibers as well
as Nuclear chain fibers.
4. There are two sensory axons that wrap around the intrafusal fibers.
a. The primary ending is a group Ia axon wrapped around the nuclear bag
and chain fibers of the spindle.
b. The secondary ending is a group II axon wrapped around the static
nuclear bag fiber and the nuclear chain fibers but NOT the dynamic nuclear bag fiber.
c. When the muscle is stretched, the intrafusal fibers are elongated which
causes the primary and secondary endings to depolarize. Stretch of intrafusal
fibers causes increased firing rate of the afferent axons.
d. The primary endings are sensitive to the rate of change in muscle length
which is referred to as velocity sensitivity. Higher firing rates of the primary
endings occur during faster stretches.
3. We can see the differences in the 1? and 2? endings by recording their firing
rates during various types of stretches. A linear stretch increased the firing rate of
both 1? and 2? endings. A brisk tendon tap only increases the firing rate of the
primary ending. This indicates that the primary endings are not only sensitive to the
length of the muscle but also to the rate of change of the length. Primary nerve
endings are especially sensitive to very small stretches.
4. If an intermittent stretch in the form of vibration is applied to the muscle, only
the primary afferents have an increase in firing rate. The intermittent stretch is
occurring too fast to affect the steady state firing of the secondary endings.
5. The motor endings regulate the sensitivity of the muscle spindle. Principles
of Gamma Activation
a. Axons from gamma motor neurons in the ventral horn of the spinal
cord terminate near the ends of the nuclear bag and chain fibers where the contractile
elements are located.
b. Input from the gamma motor neuron stimulates a contraction at the
ends of the intrafusal muscle fibers which causes them to become more taut.
c. The more tight or stretched the intrafusal fibers, the higher the firing
rate of the sensory axons thus increasing spindle sensitivity.
**
The muscle spindle is also sensitive during muscle contraction
1. It is clear that the muscle spindle is capable of conveying information to the
CNS about the muscle when it is stretched. However, during states of muscle
contraction the muscle spindle would be rendered incapable of assessing the status of
the muscle because the intrafusal fibers would be put on slack.
2. The CNS compensates for this through a process called alpha-gamma
coactivation. The CNS stimulates alpha and gamma motor neurons simultaneously.
3. The extrafusal fibers contract due to firing of the alpha motor neuron.
The intrafusal fibers are prevented from going slack because the gamma
motor neurons cause the intrafusal fibers to contract and remain tight.
4. Alpha-gamma coactivation is an important component of normal movement
because it enables the muscle spindle to convey information about the rate of change
of the muscle length. The CNS can then adjust or correct the movement trajectory.
Principles of Gamma Activation
a. stimulation of gamma MNs results in contraction of the intrafusal
fibers thereby tightening the muscle spindle and ensuring its sensitivity
b. gamma MNs are most responsive to descending input from the brain and
show little or no response to peripheral input. This means that higher centers
can control the sensitivity of the muscle spindle by activating or biasing the
gamma MNs.
c. alpha gamma coactivation occurs under most conditions but level of
activity may be higher in gamma
MNs. This is called gamma biasing
- gamma biasing occurs in one of three ways based on type of gamma
- MNs there are two types of gamma
- MNs: static and dynamic dynamic supply the dynamic nuclear bag fiber
static supply the static nuclear bag fiber and the nuclear chain fibers static
and dynamic gamma biasing means that both types of MNs are activated
before a movement which results in increased sensitivity of both primary
and secondary endings
- dynamic gamma bias increases the sensitivity of only the dynamic
nuclear bag fiber, therefore only the primary ending will be sensitive
- as we have already seen the primary ending detects rapid changes
in length and are especially sensitive to small length changes.
- Thus, dynamic gamma bias is best suited for maintaining spindle
sensitivity during small postural adjustments.
- Static gamma bias: primarily the static gamma MNs are activated prior
to and during a movement.
- because static gamma MNs supply most of the intrafusal fibers in
the spindle, all but the dynamic bag fiber, they will affect the sensitivity of both
primary and secondary endings.
- static gamma bias keeps shortened spindles active during small
length changes as well as prevents their slackening during large changes.
The Golgi Tendon Organ
1. The Golgi Tendon Organs (GTO) are located within the collagen at
the myotendinous junction.
2. Each GTO is innervated by a group Ib axon which intertwines with the
collagen fascicles.
3. Action potentials are elicited from the group Ib axons when the collagen
is deformed by tension developed during muscle contraction.
The muscle spindle is sensitive to stretch, muscle length, and rate of stretch while
the GTO is sensitive to tension and force of muscle contraction.
Why do we need GTO?
1. To prevent muscle damage due to excessive force generation.
2. To prevent fatigue of a motor unit.
Clinical Importance of Muscle Spindles
Muscle spindles are a key factor in determining muscle tone.
1. Muscle tone is the resistance of a muscle to passive stretch.
2. Muscle tone is assessed by passively flexing and extending the limb and feeling
the degree of resistance encountered.
3. Under normal conditions, the muscle spindle and stretch reflex are
making continual adjustments to maintain the optimal length of the muscle.
The optimal length of the muscle is the sum of the excitatory and inhibitory inputs
reaching the motor neuron from the brain.
4. Normal muscle tone allows us to stand erect and overcome the pull of gravity. It
also provides a spring like quality to the muscle which means that muscles can store
energy and release it during movements such as running.
5. Normally muscle tone is relatively low; however, lesions of the CNS produce
dramatic increases in muscle tone known as hypertonus or spasticity; or decreases in
tone referred to as hypotonus or flaccidity.
6. There are at least three levels within the spinal cord at which alterations in neural
input will result in tone changes.
a. The CNS can change the amount of fusimotor activity; i.e. the firing rate
of the gamma motor neurons, thereby changing the sensitivity of the muscle spindle.
b. Changes in direct descending inputs to the alpha motor neurons will
reset the optimal length of the muscle, inducing changes in the activity of the
stretch reflex.
c. Presynaptic changes in the effectiveness of inputs to the motor
neurons will drive the firing rate of the motor neuron.
What are the supraspinal structures involved in the control of muscle tone?
1. Damage to supraspinal structures results in hypotonia or hypertonia depending on
the structures involved.
2. If only the pyramidal tract is lesioned, hypotonia results indicating that the tract
plays a facilitory role in the control of tone.
3. however, if the primary motor cortex or extrapyramidal structures are
lesioned hypertonia or spasticity is seen. Indicating that they play an inhibitory role in
the control of tone.
4. extrapyramidal structures include:
a. Lateral Vestibular Nucleus: direct excitation of alpha MNs to the
extensor muscles of the limbs, normally inhibited by cortex and cerebellum
b. Reticular formation: loss of inhibitory control over the reticular formation
by the cortex, cerebellum, and striatum, leads to excitation of flexor and extensor
MNs of the limbs.
c. Red Nucleus: provides excitatory input to flexor MNs in the cervical cord
Decorticate vs Decerebrate Posturing or Rigidity
1. two clinically relevant conditions that you may see following CNS trauma in
the comatose patient.
2. By applying a startling painful or auditory stimulus to the comatose patient it
is possible to localize a lesion in the brainstem.
3. Damage between the red nucleus and the vestibular nuclei results in what is known
as decerebrate posturing.
4. Decerebrate Posture: the comatose patient will extend the upper and lower limbs.
a. Due to the loss of inhibitory influence from the cortex on the lateral
vestibular and reticular nuclei. The LVN and reticular system facilitates activity
in the alpha MNs to the limb extensors and rigidity ensues.
5. If the damage is located rostral to the red nucleus, in the area of the thalamus
and hypothalamus, decorticate rigidity occurs.
6. Decorticate Posture: The lower limbs will extend and the upper limbs will flex.
Because the RN has not been damaged, it is thought that the rubrospinal
axons facilitate upper extremity flexion.
Muscle Spindle Afferents Influence Alpha Motor Neurons and Produce
Movement
1. The simplest motor output that results directly from activation of the muscle spindle
is the stretch reflex.
2. The Ia afferent input enters the spinal cord through the dorsal root and branches.
Some of the branches terminate directly on motor neurons to the same muscle,
some synapse on motor neurons to synergists or antagonists and some end on
interneurons.
3. The simple stretch reflex
First: a brisk, passive stretch of a muscle which increases the firing rate of
the
group Ia afferents in the muscle spindle.
Second: The action potentials enter the spinal cord and make excitatory
synapses with three classes of neurons
Homonymous Motor Neurons: Cells to the same muscle.
Motor neurons of Synergist Muscles: Muscles that produce the same
action at the same joint.
Interneurons: Neurons whose cell bodies and axons are located in the grey
matter of the spinal cord. Interneurons synpase on motor neurons to the antagonist
muscle, the opposing muscle.
Third: The motor neurons stimulate contraction of the stretched muscle and
its synergists. The interneurons inhibit the motor neuron to the antagonist
muscle thereby minimizing resistance. This dual action is called reciprocal
innervation.
Fourth: The result is contraction of the stretched muscle.
Complex movements are the result of convergent input to interneurons and motor
neurons
1. Excitatory and inhibitory input from the brain, spinal cord and muscle converges
on the interneurons. Thus, the output of the interneuron is the sum of these
inputs.
2. The interneurons serve as gates and determine whether peripheral inputs reach
the motor neuron.
3. Specific reflex responses may be inhibited because descending brain systems
override the peripheral input at the level of the interneuron.
There are Three types of interneurons
1.Ia inhibitory interneuron: Allows higher centers to control the activity of
opposing muscles at a joint through a single command. A descending signal that
stimulates muscle contraction at a joint will also simultaneously relax the opposing
muscles.
2. Renshaw Cells: These cells are stimulated by the motor neuron and then inhibit
the same motor neuron which is called recurrent inhibition. The renshaw cell
also inhibits Ia interneurons. Thus, stimulation of the renshaw cell controls the
excitability of the motor neurons around the joint.
3. Group Ib Inhibitory Interneurons: The afferent fibers from the Golgi Tendon
Organ synapse on Ib inhibitory interneurons which decrease the firing rate of
the homonymous motor neuron. The Ib fibers also synapse on an excitatory
interneuron which stimulates the motor neuron of the antagonist muscle. In this way,
muscle contraction is reduced and opposing resistance is increased around the joint.
A convergence of input from joint afferents, cutaneous afferents and descending
systems also occurs on the Ib inhibitory interneuron thereby coordinating movements
that rely on an integration of multiple inputs.
Organization of complex movements is done at the level of the spinal cord by
several processes some of which are used to elicit simple movements such as the
stretch reflex.
1. Divergence
A. A single stimulus synapses on many neurons including MNs and interneurons.
B. It enables a single focal stimulus to produce coordinated contraction of
several muscle groups and inhibition of others through divergent synapses on
many cells.
2. Convergence
A. Most neurons in the spinal cord receive input from higher centers,
interneurons and peripheral receptors. The output of the MN is the sum total of all
the excitatory and inhibitory input it receives.
3. Gating by interneurons
A. the interneurons play a very big role in mediating coordinated muscle
contractions and joint movements.
B. Input from the periphery and the CNS converge on the interneuron. The
output of
the interneuron will reflect the majority of its inputs.
C. In this way, the interneuron serves a gating function. Signals are passed on
or kept from the MN depending on the activation level of the interneuron.
D. gating allows higher centers in the CNS to preselect a particular response
without having to receive and process afferent input directly.
- For example, the CNS may increase the acitivity level of a particular set of
interneurons so that only small excitatory input will be needed to fire the cell.
4. Presynaptic inhibition
A. descending systems synapse on axon terminals of the presynaptic cell rather
than directly on the interneuron. The action potential of the presynaptic cell
is dissipated before neurotransmitter is ever released thus inhibiting input to
the postsynaptic cell.
5. Reverberating circuit
A. interneurons are arranged in such a way as to be self stimulating.
B. excitation of the interneuron causes excitation of other interneurons
which converge back on the original interneuron.
C. these circuits control the temporal aspects of the response so that the
response can outlast the stimulus.
Central Pattern Generators are examples of reverberating circuits.
Coordination of Whole Limb Movements via Spinal Mechanisms
1. The spinal cord is capable of producing complex, bilateral movements of
the limbs without descending brain input.
2. The flexor withdrawal reflex is an example of the movement complexity
mediated by the interplay of afferents, interneurons and motor neurons.
First: A painful stimulus elicits action potentials in small A? fibers. These
fibers synapse on multiple excitatory interneurons.
Second: The some of the interneurons synapse on ipsilateral motor neurons to
the flexors or extensors. Some of them synapse on motor neurons to the
contralateral
limb.
Third: The ipsilateral flexors are excited while the extensors are inhibited
thereby allowing the limb to be removed from the painful stimulus. At the same time,
the extensors to the contralateral limb are stimulated and the flexors inhibited so
that the opposite leg can provide support.
Fourth: This interneuronal pathway is an efficient means to coordinate
limb movements across the pelvic girdle and appears to operate during
voluntary movement as well.
3. Locomotion is a sophisticated movement mediated by circuits in the spinal cord.
A. An as yet undefined set of neural circuits within the spinal cord are capable
of generating locomotion in the absence of any descending brain input.
B. Animals with a complete transection of the spinal cord will walk
when placed on a moving treadmill. The transection is at midthoracic levels and
the hindlimbs take alternating, rhythmic steps. The sequence of muscle activation is
complex and similar to that in normal animals.
C. Circuits responsible for these movements are termed Central Pattern
Generators and appear to be present at birth. They are an integral component of the
spinal cord.
D. There are central pattern generators for each limb. Each CPG can
operate independently but are usually linked to one another.
E. While afferent input from the limb moving on the treadmill belt is important
to stimulate stepping in the transected animal, it is not necessary. Stepping can
be elicited in animals with no afferent input reaching the cord by
administration of L-dopa which demonstrates that the CPG can function in the absence
of afferent input.
F. The CPGs are able to adapt to changing environments. A spinal animal on
a treadmill will lift the hindlimb higher as if to clear an obstacle if the top of the foot is
stimulated during the swing phase. The same stimulation during stance
produces greater hindlimb extension. Thus, the CPG adapts to afferent input and
more importantly responds in a context specific manner.
**
ANSWERS TO REVIEW QUESTIONS
2. a. Quick postural adjustments like slipping on the ice,
b. Sitting, Standing, slow walking
c. Quick movements: ie, pitching a baseball; muscle twitches
d. Stationary Positions; holding a pose; slow movements like Tai Chi
- Sleeping on a moving subway train: Movement is imposed on the body
which requires quick adjustments of postural muscles, therefore, dynamic
is high. Static is low because the muscles are at rest when the
perturbations occur.
- Standing to deliver a speech: static-moderately high; dynamic-low
(unless your knees are shaking due to apprehension J).
- Riding a horse: Static high because trying to maintain a posture
with movement imposed on it. Dynamic would also be high especially
when unexpected perturbations occur like jumping over a ditch.
f. Yes, the resting length of the muscle is usually shorter so that there
is greater overlap which makes sense given that one of the determinants
of tone is actin-myosin overlap.