ACTION POTENTIAL MEASUREMENT, NERVE-TRUNK PROPERTIES
EXTRACELLULAR RECORDING: Non-invasive recording of action potentials by placing electrodes outside the neuron, on the skin. - MONOPHASIC RECORDING: Utilizes one electrode plus a ground electrode. The electrical potential outside the neuron is then recorded as action potentials pass through.
- DEPOLARIZATION is represented as an upward peak on the graph, where up is more negative and down is more positive. As the action potential passes the electrode, the outside of the neuron becomes more negative, as Na+ flux in.
- BIPHASIC RECORDING: Utilizes two electrodes and measures the potential difference between them.
- Depolarization passes the first electrode: The first electrode becomes negative with respect to the second electrode.
- Negative (upward) deflection on graph.
- Depolarization passes the second electrode: The two electrodes are now both depolarized and therefore have the same volt-potential.
- Graph returns to zero-line.
- Depolarization then reaches second electrode while first depolarizes.
- Positive (downward) deflection on graph.
- THRESHOLD POTENTIAL: With external stimulation, large axons are excited more easily (have a lower threshold potential) than small axons because they have a lower internal resistance.
AXON DIAMETER: Many properties of nerves vary according to axon diameter: - CONDUCTION VELOCITY: There is a linear relationship between axon diameter and conduction velocity:
- Myelinated Axons: CONDUCTION VELOCITY (m / sec) = 6 x Diameter (micron)
- Unmyelinated Axons: CONDUCTION VELOCITY (m / sec) = 1.7 x Diameter (micron)
- EXTRACELLULAR EFFECTS:
- The amplitude of the extracellular action potential varies directly with cell diameter.
- The threshold for extracellular stimulation varies inversely with axon diameter. The larger the axon, the lower the stimulus threshold.
- LOCAL ANESTHETICS: Small axons are blocked before large axons.
- LARGE AXONS are more sensitive to (blocked first by):
- Temperature change
- Pressure change
- Extracellular positive stimulation
- Asphyxia, anoxia
COMPOUND ACTION POTENTIAL: An extracellularly stimulated action potential that has graded stimulus intensity. It only occurs with artificial stimulation. - SUMMATION: The potential shows summation of the individual axons contained within the nerve being stimulated.
- At low stimulus intensity, only the largest axons will be stimulated.
- At higher intensity, more axons will be stimulated, and a higher resultant stimulus intensity will be recorded.
CLASSIFICATION OF NERVE TRUNKS: - ELECTROPHYSIOLOGICAL CLASSIFICATION: Use capital letters. Based on conduction velocities.
- This scheme is used for all nerves but muscle spindle afferents.
- Cutaneous Afferents use this designation.
- CATEGORIES:
- A-alpha = fastest nerves, 120 m / sec: Alpha Motor neurons innervating extrafusal muscles
- A-beta
- A-gamma = Gamma motor neurons innervating intrafusal muscle.
- B
- C
- ANATOMICAL CLASSIFICATION: Use roman numerals. Based on axon diameter.
- Only Muscle Spindle Afferents use this designation.
- CATEGORIES:
- I (largest nerves) = Primary muscle spindle and Golgi Tendon afferents
- II = Secondary muscle afferents; skin, touch, and pressure afferents
- III = Skin, temperature, fast pain; Autonomic
- IV = slow (dull) pain fibers; Autonomic
BELL-MAGENDIE LAW: Afferent nerves enter over the dorsal Root, and efferent nerves leave through the Ventral Root. - EXCEPTION: Some Pelvic Viscera pain and temperature axons enter the spinal cord through the Ventral Root.
- The Dorsal Root Ganglion is still in dorsal root, but the post-ganglionic axons bends around the Rami Communicans and actually enters the spinal cord through the Ventral Root.
- CLINICAL: Thus, sectioning of dorsal roots will not completely alleviate pelvic pain.
MEASURING CONDUCTION VELOCITY: Conduction velocity of a motor axon cannot be measured directly, because it would include the time for the potential to cross neuromuscular junction and to conduct through the muscle membrane. If you want to just measure conduction through the nerve itself: - PROCEDURE:
- Place two electrodes on the forearm, on two different parts of the Median Nerve.
- Stimulate the Abductor Pollicis muscle.
- On the graph, record the different in time (latency period) between stimulation and muscle flexion.
- Use equation above to get conduction velocity, m / sec
- PAIN FIBERS: In measuring sensory nerves, sharp pain fibers (pin prick) travel faster than temperature fibers. So, a withdrawal reflex from sharp pain occurs faster than a withdrawal reflex from a hot stove.
- LOCATING AXIAL NEUROPATHIES: We can't directly, non-invasively stimulate nerves that aren't in the extremities, but we can determine conduction problems by using a REFLEX ARC.
- SEGMENTALLY stimulate a sensory nerve going up the arm, and induce a reflex. If a local stimulation shows normal velocity, but the reflex took too long of a time, then you can deduce that their must be a conduction problem in the proximal part of the reflex.
- ELECTROMYOGRAM (EMG): Test to measure muscle contractility and stimulation of motor nerves.
- The amplitude of the muscle response tends to drop off as you go from distal to proximal, by about 15%
- REPEATED STIMULATIONS: The normal response should show the same magnitude for each stimulation with repeated stimulations of low frequency. With higher frequency (i.e. tetanic stimulation), normal response should be a tetanic graph (increasing tension with decreasing magnitude on each successive stimulus).
- MYASTHENIA GRAVIS: On an EMG it will show a Decrescendo (decreasing magnitude) graph with repeated stimulations.
- Low frequency stimulations (non-tetanic) are used to diagnose MG.
- MG is an auto-immune disorder against the post-synaptic neuron (nerve terminal)
- MYASTHENIC (EATON-LAMBERT) SYNDROME: On an EMG it will show a Crescendo (increasing magnitude) graph with repeated stimulations.
- High frequency stimulations (Tetanic Stimulation), which hurts a lot, are used to diagnose Myasthenic Syndrome.
- This syndrome is an auto-immune disorder against the pre-synaptic neuron.
- SPINAL CORD, SPINAL CORD REFLEXES
MOTOR UNIT: An alpha-Motor Neuron, plus all of the muscle cells it innervates.- alpha-Motor Neurons innervate extrafusal muscles.
- Final Common Pathway
- Any given muscle cell is innervated by only one alpha-Motor Neuron.
- INNERVATION RATIO: The number of alpha-neurons innervating a whole muscle (innervation density) depends on the amount of control over the muscle we need.
- Extraocular Muscles = 9 : 1 (9 muscle cells to 1 neuron) ratio, high innervation density.
- Postural Muscles = 2000 : 1 (2000 muscle cells to 1 neuron) ratio, low innervation density.
- OBLIGATORY, NON-GRADED STIMULATION: Every time an alpha-neuron is fired, it will cause an action potential in every muscle cell it innervates. There are no graded or partial potentials.
- MYASTHENIA GRAVIS and other pathologies may prevent an action potential from happening with every neuron firing -- but this is pathological and not the normal circumstance.
- MOTOR NEURON POOL: All of the motor neurons that innervate a single muscle. They are arranged close to each other in the ventral horn, according to somatotopic organization:
- SPINAL CORD ORIENTATION: The more dorsolateral you go, the more you go distally away from the midline:
- DORSOLATERAL Part of Ventral Horn: Innervates Extremities Muscles
- VENTROMEDIAL Part of Ventral Horn: Innervates Axial Muscles
- FLEXORS: Nerves going to flexors tend to lie dorsally.
- EXTENSORS: Nerves going to extensors tend to lies ventrally.
FORCE TRANSDUCTION: Twitch Tension in a muscle is increased by increasing the frequency with which alpha-motor neurons are fired.- With high frequency firing, the muscle doesn't get a chance to completely relax before the next action potential.
- Tetanus is maximal twitch tension.
- PRINCIPLE OF ORDERLY RECRUITMENT ACCORDING TO SIZE: INTRACELLULAR, physiological stimulation of nerves, the smallest axons are stimulated first (have the lowest threshold), and largest axons are stimulated last.
- This is another way to increase the force with which a muscle contracts: "Recruit" more alpha-neurons to fire on the muscle. In this case, again, the smallest neurons will fire first (small twitch tension), and larger neurons will fire later (larger twitch tension).
- V = IR: Small neurons have a higher resistance, which means they will show a stronger depolarization (V) for the same current (I).
- That's why they fire first. This is the opposite of external stimulation, where smaller neurons are stimulated last.
- In physiological stimulation, smaller neurons have a smaller threshold potential than larger neurons.
SLOW -vs- FAST TWITCH MUSCLE SLOW TWITCHFAST TWITCHalpha-Motor Neuron DiameterSmallLargeConduction VelocityFastSlowMuscle Cells innervated (motor unit size)Fewer cells innervated, and with a smaller diameterMore cells innervated, with a larger diameterTwitch TensionSmall tensionLarge tensionContraction SpeedSlow speed of contractionRapid contractionExtracellular spike size (magnitude)SmallLargeMetabolismOxidative (lots of mitochondria)Glycolytic (few mitochondria)Capillary SupplyHighLowResistance to fatigueHigh resistance to fatigueEasily fatiguedMuscle ColorRed (from mitochondria)WhiteFunctional AdaptationGenerate small forces over a long period of time -- EnduranceGenerate large forces for a brief time -- Sprint
MUSCLE SPINDLE: Intrafusal muscle fibers are innervated by afferent nerves that send signals back to the CNS about the muscle's contractility. The muscle spindle is arranged in parallel with extrafusal muscle.- Two different types of muscle fibers: They run parallel to each other in the muscle spindle. They both have respective equatorial and polar regions.
- BAG FIBERS: The velocity component of the muscle spindle. These fibers convey how quickly the muscle spindle is changing length.
- EFFERENT INNERVATION is by Dynamic Gamma Efferents, which serves to increase the sensitivity of the velocity component.
- AFFERENT INNERVATION is by IA Afferents only, which form Annulospiral Endings
- CHAIN FIBERS: The length component of the muscle spindle. These fibers convey the spindle length at any instant in time.
- EFFERENT INNERVATION is by Static Gamma Efferents, which serves to increase the sensitivity of the length component.
- AFFERENT INNERVATION is by both IA (Annulospiral) and IIA Afferents (Flower Spray)
- Two different regions of the muscle spindle:
- EQUATORIAL REGION: Contains muscle cell nuclei, and no actin or myosin. It behaves like a spring.
- AFFERENT INNERVATION is by Muscle Spindle Ia Afferents. When the spindle is stretched, these afferents fire.
- Stretch Muscle ------> Increase Ia and IIa firing rate
- Contract Muscle ------> Decrease Ia and IIa firing rate
- POLAR REGION: Contains striated muscle, actin, and myosin.
- EFFERENT INNERVATION is by Static Gamma Efferents
- Gamma Firing ------> Contract polar region ------> Stretch whole spindle ------> Increase Ia Afferent firing rate
- IA AFFERENT NERVES: They synapse with alpha-Motor Neurons that go back to the same muscle.
- "Local Sign": The response is confined exclusively to the muscle cell from which the signal originated.
- RAMP AND HOLD EXPT: Stretch a muscle and keep it stretched, and IA afferents will detect both the velocity and length of the muscle.
- They show a marked increase in activity while the muscle is being stretched, then they drop back down once stretching ceases, although they drop down to a higher basal level than before.
- ANNULOSPIRAL ENDINGS: They form annulospiral endings, on both bag and chain fibers, on the equatorial region of the spindle.
- IIA AFFERENT NERVES: Their pathway is more complex. The connection is not monosynaptic but rather involves interneurons.
- RAMP AND HOLD EXPT: Stretch a muscle and keep it stretched, and IIA Afferents will detect only length of muscle spindle.
- They show an increase in firing-rate as muscle is being stretched, and they maintain the new firing frequency once the muscle is being held at the new length.
- FLOWER SPRAY ENDINGS: They form "flower spray" endings on the polar regions of the spindle, which help them detect the current muscle length.
- STATIC GAMMA EFFERENT NERVES: They increase the length sensitivityof the muscle spindle.
- They innervate Chain fibers in the polar regions of muscle spindles.
- They bring about strong contraction in the poles of the spindle.
- FNXNS in the Muscle Spindle:
- Static Gammas increase the sensitivity of IA afferents and IIA afferents to change in spindle length. IA and IIA fibers will fire with higher frequency, in response to less change in length.
- Static Gammas prevent unloading (temporary pause) of spindle afferents, which occurs with spindle shortening.
- DYNAMIC GAMMA EFFERENT NERVES: They increase the velocity sensitivityof the muscle spindle. That is, under the influence of Dynamic Gammas, the spindle will respond more quickly to a faster rate of change of spindle length.
- They innervate Bag fibers.
- They increase muscle tension but there is no contraction -- i.e. spindle length doesn't change.
- FNXN: They produce a large increase in the velocity sensitivity of muscle spindle IA afferents. Dynamic Gammas do not affect IIA afferents.
GOLGI TENDON ORGAN: The muscle receptor responsible for the Inverse Stretch Reflex.- STRUCTURE: It is a capsule of elastic fibers, in series with (i.e. attached to the end of) 1% of all extrafusal muscle fibers.
- 99% of extrafusal fibers do not connect to the Golgi Tendon Organ.
- FNXN: When Golgi Tendon stretches, it will decrease alpha-Motor Neuron activity back to the same muscle, preventing further contraction and reducing muscle tension.
- Also it will send muscle information back to cerebellum.
- The GTO increases muscle compliance, as in muscles needing to "give" a little (by lengthening to absorb shock) when jumping off a roof and landing on feet.
- Compensation for fatigue.
- 1B AFFERENT NERVES: They innervate the Golgi Tendon Organ. Stretching of the Golgi Tendon fire these nerves.
- They goto spinal cord ------> SYNAPSE with INHIBITORY INTERNEURON ------> Inhibit alpha-Motor Neuron activvity back to same muscle.
STRETCH REFLEX: Contraction of a muscle elicited by stretch of the muscle, such as the patellar tendon reflex.- AFFERENT LIMB: Muscle spindle IA Afferents.
- EFFERENT LIMB: alpha-Motor Neurons.
- PATHWAY: Monosynaptic. Stretch Muscle ------> Increase firing rate of IA Afferents ------> Fire alpha-Motor Neurons back too same muscle ------> increase muscle tension.
- EXPT: Decerebrated Cat soleus muscle
- Experimenter did a Ramp-and-Hold experiment, stretching the muscle. Muscle tension increased as he stretched the muscle, due to the Stretch Reflex. After a certain point the muscle tension stopped increasing.
- CUT DORSAL ROOTS and the tension was even greater, due to lost inhibition by the Vestibulospinal Tract.
INVERSE STRETCH REFLEX: Once you stretch a muscle past a certain threshold, the rigidity will "melt away" and the muscle will stretch easily. Past the threshold, the muscle is undergoing the inverse stretch reflex.- AFFERENT LIMB: Golgi Tendon Organ, IB Afferents
- EFFERENT LIMB: alpha-Motor-Neuron disynaptic inhibition
- PATHWAY: The reflex is disynaptic. Stretch Muscle past threshold ------> Golgi Tendon Organ stretches ------> IB Afferents fire ------> SYNAPSE with INHIBITORY interneuron in spinal cord ------> DECREASE alpha-Motor Neuron Activity back to same muscle ------> Decrease muscle tension ------> muscle lengthens easily
WITHDRAWAL (FLEXION) REFLEX: Remove hand from a burning stove, for example.- Paraplegia / Quadriplegia: It causes an increased Withdrawal Reflex, and it may also result in unintended autonomic responses such as defecation, urination.
- C FIBERS: Pain fibers initiate the reflex.
- PATHWAY: C-Fiber activation ------> Dorsal Root ------>Excitatory synapses to alpha-neuron and gamma-neuron ------> contraction of same muscle.
- Activation of the gamma neuron will cause activation of IA Afferents, which will then initiate the stretch reflex ------> more alpha-activation.
- The net result of this is that you get a large, long lasting reflex. The reflex itself can easily outlast the original pain stimulus.
- There is also a recurring excitatory circuit, some excitatory interneurons will send fibers back to other excitatory interneurons, which potentiates the original signal in the spinal cord.
RECIPROCAL INNERVATION: IA Afferents from an extensor muscle will synapse with an interneuron that inhibits the opposing (i.e. flexor) muscle.- IA AFFERENTS therefore have two monosynapses in the spinal cord:
- Excitatory (EPSP) to the alpha-Motor Neuron of the same muscle
- Excitatory interneuron ------> Inhibitory (IPSP) to the alpha-Motor Neuron of the opposing muscle.
- The inhibitory arm of the reflex is disynaptic, while the excitatory arm is monosynaptic.
CROSSED EXTENSOR REFLEX: The contralateral reflex for the withdrawal reflex. Step on a tack, and you withdraw one foot while extending the other.- PATHWAY: Pain fibers synapse with two interneurons in spinal cord -- one to ipsilateral side and one goes across ventral white commissure to contralateral side.
- IPSILATERAL will then make two synapses, to cause FLEXION of the ipsilateral limb.
- EXCITATORY to ipsilateral flexor muscle.
- INHIBITORY to ipsilateral extensor muscle.
- CONTRALATERAL will then make two synapses, to cause EXTENSION of the contralateral limb.
- EXCITATORY to contralateral extensor muscle.
- INHIBITORY to contralateral flexor muscle.
MUSCLE TONE DISORDERS: Hypotonia and Hypertonia arise from disorders in the sensitivity of alpha-Motor Neurons.- HYPOTONIA: Decreased alpha and gamma neuron excitability. Diminished reflexes and flaccid paralysis.
- Examples: Early phase of spinal cord transection
- HYPERTONIA: Increase tonic stretch reflex, i.e. the response to muscle length when the muscle is not moving. Sustained contraction at rest, increased tonic stretch reflex, increased muscle stiffness
- Examples: Decerebrate Rigidity (UMN Paralysis), Parkinson's Disease
- SPASTICITY: Increased phasic stretch reflex, i.e. the response to muscle velocity when it is stretching. The faster the stretch, the worse is the resistance to the stretch.
- Examples: Late phase of spinal cord transection, Motor Cortex / SMA lesions.
- Factors that contribute to Spasticity:
- Increased synaptic efficacy, i.e. strength of response at a synapse
- Collateral Sprouting of axon terminals, to replace lesioned axons. In the end this can result in higher sensitivity than originally.
- Loss of presynaptic inhibition ------> alpha-Motor Neurons fire more frequently and/or more readily.
- (Minor Contributor): Gamma Efferent hyperactivity.
- CLONUS: Rhythmic series of contractions brought about by quick stretch of a spastic muscle. Clonus can occur with spastic muscles.
- It is a self-sustaining Cycle: Spastic muscle stretch ------> IA fire outburst ------> alpha-Motor strong activation -------> Reflex contraction and muscle shortening ------> ------> Rebound lengthening ------> ------> cycle repeats
SPINAL MUSCULAR ATROPHY (SMA):- Types of Spinal Muscular Atrophy:
- ACUTE SMA 1: Onset at birth and death before age 2
- SYMPTOMS: Death ultimately from failure of respiratory muscles and respiratory infection.
- INTERMEDIATE (Werdnig-Hoffman) SMA 2: Survival beyond 4 years.
- SYMPTOMS: Diminished reflexes and general muscle weakness. Absent reflexes by age 2.
- Scoliosis.
- Death ultimately by respiratory complications.
- CHRONIC (Kugelberg-Welander) SMA 3
- SYMPTOMS: First presentation is weakness in the proximal lower limbs, then upper extremities later (this pattern holds for all types of SMA).
- GENETIC BASIS:
- SURVIVAL MOTOR NEURON (SMN): The SMN gene is defective (duplication mutation) in virtually all cases of SMA.
- The SMN gene is located on Chromosome 5
- FNXN: The protein product is a membrane receptor. They think that it may be a receptor for a muscle-derived trophic substance. Details are unknown.
- NEURONAL APOPTOSIS INHIBITORY PROTEIN (NAIP): The NAIP gene is defective (duplication mutation) in many SMA cases, however this defect is not required for SMA.
- The NAIP gene is located on Chromosome 5
- The presence and severity of the NAIP defect correlates with how severe the SMA case is.
- FNXN: The NAIP protein product is thought to prevent apoptosis (programmed cell death) during development. Thus in the absence of NAIP, some neurons that were supposed to survive actually die instead.
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