Motor function: brainstem and spinal cord Flashcards
What is a neuromuscular junction?
A synapse between a muscle fiber and a branch of motor neuron axon. The axon of a motor neuron divides into a number of branches at the surface of the muscle fiber. Each branch ends in a bouton.
How wide is the cleft of a NMJ?
50nM across
The postjunctional membrane, the endplate, which is thrown into folds, has a high density of what receptors?
nicotinic acetylcholine receptors under the active zones where acetylcholine (ACh) is released.
What is the structure of the basal lamina of the cleft?
It is a collagenous basement membrane to which is bound acetylcholinesterase (AChE). Soluble forms of the same enzyme are also secreted into the cleft.
What happens when ACH binds to Nicotinic acetylcholine receptors (nAChR)?
These are ligand-gated ion channels that mediate fast ACh transmission. Binding of ACh opens the channel, allowing Na+influx and K+ efflux. The reversal potential for this current is close to 0 mV, so activating nAChR causes depolarization.
What occurs after a spontaneous release of a single quantum of ACh at the nmj?
This causes a 0.4 mV depolarization at the endplate called a miniature endplate potential (mepp).
The arrival of an action potential at the motor nerve terminal triggers what?
Triggers the release of 200–300 quanta producing numerous mepps which sum to produce a depolarization to about -20 mV, an endplate potential (epp). This greatly exceeds the threshold for activating voltage-dependent sodium channels in the muscle membrane, so an action potential which is propagated over the muscle fiber membrane.
How long does it take for the concentration of AcH in the NMJ to reach 1mM, and how long does it take to fall back to baseline?
within about 200 μs of the arrival of an action potential at the motor nerve terminal but within a millisecond or so the Ach concentration has fallen back to baseline levels because of the high activity of AChE in the cleft.
How is AcH removed from the cleft?
AChE hydrolyzes ACh to choline and acetate. Choline is taken back into the nerve terminal via a Na+ -dependent transporter.
What is the mechanism of action of Nondepolarizing muscle relaxants, such as the tetrahydroisoquinoline derivatives (e.g., the prototypical d-tubocurarine, atracurium) and the aminosteroids (e.g., pancuronium)?
They are competitive antagonists of nAChR. The duration of action of these drugs ranges from 15 to 180 minutes.
What is the mechanism of action of neostigmine to reverse action of non depolarizing muscle relaxants?
It is an AChE inhibitor that causes a rise in the concentration of ACh which then out-competes the drug for the nicotinic receptor.
Which is the only depolarizing muscle relaxant of clinical importance?
Succinylcholine
What is the mechanism of action of succinylcholine?
It is a nAChR agonist
What is the phase 1 block by succinylcholine?
Initially, agonist binding opens the nicotinic receptor channel causing persistent depolarization of the endplate. This first causes generalized disorganized contractions of muscles called fasciculations, and is followed by flaccid paralysis as muscle Ca2+ channels inactivate and the contraction mechanism fails as a result. This arises as a result of an ACh-like depolarization and so is augmented rather than reversed by AChE inhibitors.
What is a phase 2 block by succinylcholine?
With continuing exposure phase II block occurs in which the nAChR either desensitizes, or suffers open channel blockade by the drug. Phase II block can be reversed by AChE inhibitors.
Why is the duration of action of succinylcholine only 5 minutes?
Succinylcholine is rapidly hydrolyzed by circulating esterases.
What is a motor unit?
Consists of a motor neuron and the muscle fibers it innervates. In mammals each muscle fiber is supplied by only one motor neuron, however, each motor neuron synapses with anything from 6 to a few thousand muscle fibers within a single muscle. The fibers of a single unit are scattered widely throughout a muscle so no part of a muscle is controlled by just one motor unit.
What is the size of a motor unit related to?
To the precision of motor control required of a given muscle. Finely regulated muscles consist of small motor units, less finely regulated muscles have larger ones
What does a single action potential in the motor neuron cause?
A twitch (single contraction) in all of the muscle fibers to which it is attached.
What is unfused tetanus?
The contraction and relaxation of muscle fibers is loner than the muscle AP (3ms). If a volley of APs is fired (at 12HZ) and there is insufficient time for the muscle to relax between successive impulses the twitches summate to increase the force which oscillates about a plateau value.
What is fused tetanus?
As firing frequency increases (30HZ), the oscillations smooth out and the plateau reaches maximum force.
Which type of motor units are the most common?
Slow twitch (S) motor units
What are the properties of the force generated by the fibers of S motor units?
they take 50 ms to reach peak force and show little decline, even after an hour of repetitive stimulation. They are capable of exerting low forces for long periods. They form the bulk of the antigravity or postural muscles of the trunk and legs.
What are the properties of the motor neurons of the S motor units?
They are small, have low conduction velocity and long refractory periods because they contain a high density of calcium activated K channels which cause a long afterhyperpolarization.
What is the significance of the long refractory periods of S motor units?
This limits maximum firing frequencies to low rates, but fused tetanus is achieved at low frequencies (15-20 Hz)
What are the properties of the Type 1 muscle fibers of the S motor units?
They are rich in mitochondria, have high activities of Krebs cycle enzymes which fits them for high rates of aerobic metabolism and form red muscle because of their high myoglobin content.
What are the properties of the forces generated by fast twitch motor units?
They contract maximally in 5-10 ms but cannot sustain the contraction for very long. With repetitive stimuli fatigue resistant units can sustain moderate force for 5 minutes or so before a steady decline sets in that takes many minutes. Fast fatigue motor units achieve the greatest force, but with repetitive stimuli the force falls precipitously after about 30 seconds. Both FF and FR are adapted for producing rapid, large forces and so are found in muscles involved in executing fast movements.
What are the properties of the motor neurons of fast twitch motor units?
They are large with high conduction velocities. For brief periods they fire at high rates but action potential volleys are of short duration, particularly for FF units
Fast twitch units contain type 2 muscle fibers, what are the properties of these?
They form white muscle because of their low myoglobin content and require firing frequencies of 40 -60 Hz to produce fused tetanus. Type 2b (FF) are anaerobic, Type 2a (FR) are intermediate between types 1 and 2b in terms of metabolism.
How are the properties of muscle fibers and motor neurons matched for optimal performance?
Muscle fiber properties are determined by the motor neurons that innervate them. If type 1 muscle fibers are denervated and the axon of a FF unit sprouts to establish new connections with the denervated fibers, they acquite the characteristics of type 2b muscle fibers
What is a motor pool?
Formed by motor neurons that innervate the same muscle. They are topographically localised in motor nuclei of the brainstem and spinal cord
What are the properties of spinal motor nuclei?
They extend over several spinal segments. Axons of motor neurons leave the ventral horn of the spinal cord to run in the spinal nerve of the same spinal segment.
Where does the sorting of fibers destined for the same muscle but originating from different spinal segments occur?
The nerve plexuses. Axon collaterals of motor neurons ascend and descend a few segments to influence the behaviour of other motor neurons in the same pool
How is the force of a muscle contraction determined by the motor pool?
The rate at which individual motor neurons fire and the number of motor neurons in the pool that are firing.
How is the force of a contraction increased?
Small increases in force are met mostly by increased firing rate, but larger contractions involve increasing the number of active motor units, a process called recruitment.
How is the process of recruitment carried out?
It is done in an orderly manner. The earliest units to be recruited are S, followed by FR and finally FF, and order determined by the size principle. 2 effects are at work – the size of the motor neurons, and how synapses onto them are organised.
How does size of a motor neuron determine the size principle?
Small cells offer a bigger resistance to the flow of current than large ones. Ohms law states that membrane voltage = Current x resistance. Neurons in a motor pool are excited by common inputs. Therefore, for a given synaptic current input, the small cell body of an S motor neuron will have a bigger excitatory postsynaptic potential than the larger cell body of a fast twitch unit. This means that the weakest inputs recruit the S units as they have the lowest threshold for synaptic activation.
What is the second effect determining size principle?
The synaptic inputs to the three classes of motor unit are weighted in such a way that as input strength increases so motor units are recruited in the sequence S-FR-FF.
Does recruitment always obey the size principle?
No, in some instances synapses are arranged so that large motor neurons get more excitation than small ones. For eg, in humans, cutaneous afferents preferentially excite fast twitch motor units.
How are motor neurons modulated?
They are modulated by monoaminergic neurons (NA, 5-HT) that projects in the reticulospinal tracts. This enhances the response of the motor neuros to excitatory input, eg, S motor units fire tonically at 20 -30 Hz but with elevated monoamine input, Ia afferents will produce firing rates in excess of 50 Hz.
When do the firing rates of monoaminergic neurons increase?
With arousal. Modulation by NA allows the generation of higher forces from the same inout when arousal is high. Serotonin neurons fire during locomotion and their firing rate increases with speed, driving motor neurons to fire at higher frequency for a given input.
How do monoamines bring about motor neuron hyperexcitability?
By the enhancement of a depolarizing current through L-type calcium channels in their dendrites
What is a reflex?
It is a stereotyped response to a particular stimulus. When it involves the autonomic nervous system it is an autonomic reflex and the effector is typically cardiac or smooth muscle or a gland. When it occurs in the somatic nervous system it is a motor reflex and the effector is skeletal muscle
Reflexes are mediated by specialized neural circuitry called a reflex arc, what does this consist of?
A sensory neuron, a motor neuron and usually interneurons interposed between the two, which may be excitatory or inhibitory.
What are polysynaptic reflex arcs?
Reflex arcs with two or more interneurons that have three or more central synapses
What is a disynaptic reflex?
A reflex arc with only one interneuron
What is the only example of a monosynaptic reflex, where there is no interneuron?
The stretch reflex
What is usually the effect of afferents firing in a reflex arc?
A sensory neuron will form synapses with several interneurons (or motor neurons in the case of a monosynaptic reflex). Usually the effect of afferent firing is to produce quite large epsps on a few neurons and more modest epsps in a bigger group, depending on the number of synapses.
What provides for the possibility of integration in reflexes ?
The connections made by several sensory neurons on interneurons overlap
Integration at reflexes is often nonlinear, what does this mean ?
the excitation of the motor neuron can be bigger than the sum of the individual inputs, facilitation, or dominated by one input and hence little affected by additional ones, occlusion.
What is reflex latency or reflex time and what does it result from?
The time between the stimulus and response. It results from the conduction time along afferent and efferent fibers, but also includes the time taken for sensory transduction and for activation of the effector (muscle or gland). A small interval is taken up by the synaptic delay, usually between 0.5 and 1 ms.
What do reflex latencies reflect?
When conduction time is taken into account reflex latencies reflect the number of central synapses
What effect does increasing the stimulus intensity have on a reflex?
It will change the amplitude of the reflex (e.g., the amount by which a limb moves) but may also alter the form of the response by recruiting addi- tional muscles, this is called irradiation
What is the local sign?
The exact form of the reflex response depends on precisely where the stimulus is applied and so which afferents are excited
What is habituation ?
The attenuation of a reflex by the repeated application of a constant innocuous stimulus. It is caused by synaptic depression
What is dishabituation?
The return of the reflex to its baseline state. It is caused by any change to the stimulus (e.g., in its intensity
What is sensitization?
The enhancement of a reflex by a decrease in latency, increased amplitude, or irradiation caused by repeated application of a noxious stimulus. It results from increased transmitter release
What are habituation and sensitization of the reflexes examples of?
Nonassociative learning because only one stimulus is involved
What are conditioned reflexes?
reflexes that are capable of the more complicated associative learning, in which a response occurs if two stimuli are paired in time.
What is the most elementary modulation of motor unit output?
It is made by sensory input from the muscle spindles which measure the length and rate of change of length (velocity) of the muscle.
What is the muscle spindle reflex/ stretch reflex/ myotatic reflex?
Any attempt to stretch the muscle rapidly, for example by suddenly loading it, is met by contraction. It is a negative feedback mechanism which defends a constant muscle length in the face of external forces which act to perturb it.
How is a stretch reflex elicited?
by sharply tapping the tendon of any muscle. The resultant stretch causes the muscle to contract. The stretch reflex is most easily demonstrated by tapping the patellar ligament between its insertion into the tibia and the kneecap, causing the contraction of the quadriceps femoris, the powerful group of extensor muscles on the front of the thigh
The sensory side of the stretch reflex consists of the muscle spindle and its afferents. What is the structure of the spindle?
Muscle spindles lie in parallel with the standard extrafusal fibers. Each muscle spindle is a fluid- filled capsule of connective tissue, 4–10 mm long and 100 μm in diameter, containing about seven modified muscle fibers called intrafusal fibers. Intrafusal fibers have contractile ends but their central regions are noncontractile. There are two types of intrafusal fiber, nuclear bag and nuclear chain
