Excitability and Circuits Flashcards
1
Q
What is a motor unit?
A
• Motor unit- a motor neuron and the synchronous muscle fibres it innervates and exclusively controls
2
Q
What are the two different types of motor units?
A
• There are different types of motor units:
o Fast- twitch motor units
o Slow-twitch motor units
3
Q
Describe fast-twitch motor units
- Diameter
- Type of motor protein
- Muscle fibre amount
- Size of motor neurons
- Force amount
- Ability to sustain tetanic contractions
A
Specialised, large-diameter muscle fibres
Composed of fast type myosin
Contain many muscle fibres
Are controlled by big motor neurons
Can produce a lot of force in response to action potential
Cannot sustain prolonged tetanic contractions
4
Q
What are two different types of fast-twitch motor units. Describe them.
A
Divided into 2 subcategories
• Fast-fatiguing type units
o Composed of muscle fibres using anaerobic metabolism
• Fatigue-resistant type units
o Composed of fibres using aerobic metabolism
5
Q
Describe slow-twitch motor units
- Diameter
- Type of motor protein
- Muscle fibre amount
- Size of motor neurons
- Force amount
- Ability to sustain tetanic contractions
- Metabolism type
A
o Slow-twitch motor units Specialised slow-twitch muscle fibres Slow-type myosin Composed of few muscle fibres Controlled by small motor neurons Aerobic metabolism Lesser force in response to action potential Less tetanic contraction force Can sustain tetanic contraction for a long time
6
Q
What can force production in the muscle be graded by?
A
• Force production in the muscle can be graded by population code and frequency code
7
Q
What is population code?
A
o Population code- Each neuron has a distribution of responses over some set of inputs, and the responses of many neurons may be combined to determine some value about the inputs (relies on number of motor unit)
8
Q
Define frequency code
A
o Frequency code- Frequency of impulse conveys information about varying intensity of signals
9
Q
How does the frequency code influence muscle force? Describe the mechanism
A
• Muscle fibres translate increased frequency into increased force
o When only small force is needed, the weakest slow motor neurons are activated first
o If more force is required, the depolarising synaptic input increases and the same slow-twitch motor neurons fire at higher frequency, generating greater tetanic force
o If more force is needed, additional fast-type motor neurons ae activated by the synaptic drive
o Once activated, each motor unit increases its firing rate, as needed, to contribute to achieving the total force required for the task
o In principle, the higher the frequency, the greater the force produced by the motor unit (frequency code)
10
Q
What does electromyography allow and what does it record?
A
• Electromyography (EMG)
o Allows for study of activation of muscle fibres by motor neurons
o Records the small extracellular electrical currents generated as the muscle action potential propagates from the Neuromuscular junction to end of each muscle fibre
11
Q
What is the purpose of Compound Muscle Action Potentials?
A
• Compound muscle action potential (CMAPs)
o Purpose-
Examines population code during action
12
Q
What are two types of EMGs?
A
- Compound muscle action potential (CMAPs)
* Single fibre EMG recording
13
Q
How are CMAPs conducted?
A
o Process
Electrodes are attached to the skin surface directly over the muscle and the electrical potential difference between the two recording electrodes is recorded
CMAPs can be recorded in response to deliberate activation of the muscle in question by a subject
CMAPs can also be triggered artificially, by electrically stimulating the motor axons with a single impulse
14
Q
Describe how CMAP results displayed and interpreted
A
o Result
CMAP is typically a complex waveform representing the summed electrical currents produced by all the active muscle fibres within the muscle
The area of each CMAP waveform can be used to compare the relative number of muscle fibres or motor units activated at any given time.
• The greater the area, the greater the number of active muscle fibres
15
Q
What is the purpose of single fibre EMG recording
A
o Purpose-
To study the activity of individual motor units
To study frequency code and population code
16
Q
What is the process of single fibre EMG recording?
A
o Process
Specialised concentric needle electrode is pushed into the muscle close enough to an individual muscle fibre so single fibre action potentials can be recorded
17
Q
How are excitatory postsynaptic potentials produced?
A
• Production of EPSPs
o Many of the synapses on the motor neuron are glutamatergic, meaning that the bouton releases vesicle-loads of glutamate
o The quanta of glutamate bind and activate glutamate receptors on the postsynaptic membrane
o Many of the glutamate receptors are ligand-gated cation channels of the AMPA-type and the NMDA-type
o The opening of these ligand-gated cation channels results in depolarising inward currents of sodium and calcium in the motor neuron
o This produces excitatory postsynaptic potentials
18
Q
How are excitatory postsynaptic potentials studied?
A
• Studying Excitatory PostSynaptic Potentials
o Microelectrode must be inserted through individual neuron membrane
o When electrode pierces the membrane it will record a negative resting Vm (membrane potential)
19
Q
What are properties of EPSPs?
- Depolarisation time
- Amplitude in regards to action potentials
A
• Properties of EPSPs
o Each EPSP involves brief, graded depolarisation (about 15 msec)
o Amplitude of most EPSPs is not sufficient to reach the action potential threshold, except when summation occurs
20
Q
What is summation
A
o Summation-when many excitatory glutamatergic synapses on a neuron are simultaneously active, the sum of their EPSPs can push the Vm above the threshold needed to trigger a train of action potentials
21
Q
What is the relationship between membrane potential and action potential firing frequency?
A
The higher the Vm rises above threshold, the higher the action potential firing frequency
22
Q
Describe what voluntary muscles are controlled by, how these controllers are organised and how they control the muscle
A
- Voluntary muscle controlled by a group of alpha motor neurons that constitute the motor neuron pool for that muscle
- The motor neurons that control a given muscle are organised into a column extending over several spinal segments
- Axons of motor neurons leave from spinal cord via several adjacent ventral spinal roots before coming together again in a common peripheral nerve that gives rise to the muscle nerve
23
Q
Explain the size principle for motor unit recruitment and its underlying neurophysiological mechanism
A
• Slow twitch units are recruited first, followed by more powerful units until the task is achieved
o Large motor neurons (which control fast-twitch motor units) require more depolarising current to reach threshold than smaller motor neurons (which control slow-twitch motor units)
o This is because of the larger area of peripheral membrane allows more of the depolarising current to leak out through an increased number of leakage channels in larger cells
o Hence, during voluntary activation the increasing amount of depolarising postsynaptic current therefore tends to activate the small motor neurons first (those with higher input resistance), then the next largest…- This is called the size principle
The previously activated motor units stay activated- cumulative effect
24
Q
What is the relationship between neuron size, input resistance and current needed to bring it to the threshold
A
• The smaller the neuron, the higher the input resistance and the less current needed to bring it to threshold
25
What is input resistance?
Input resistance- measures current leakiness of a neuron
26
What is the recruitment threshold and its relationship with motor unit power
• Recruitment threshold- amount of force required before a particular motor unit starts being activated (measured in Newtons)
o Linear relationship between recruitment threshold and motor unit power
27
What are the seven foundation concepts for neurophysiology?
1. Selective diffusion of potassium ions across the membrane generates a negative membrane potential
2. Membrane potential depends upon the relative permeability of the membrane to sodium ions versus potassium ions
3. The potassium/sodium pump maintains the concentration gradients over seconds and minutes
4. Neuronal signalling is rapid
5. Action potentials are generated by voltage-gated ion channels
6. The neuromuscular junction is an example of a chemical synapse
7. Excitation-contraction coupling in skeletal muscle fibres
28
What is the purpose of the Nernst equation?
• Nernst equation summarises the interaction between chemical and electrical driving forces for a particular ion
29
What is the Nernst potential for potassium?
• Nernst potential for potassium (Ek)- the membrane potential at which electrical driving force on potassium ions (opposite changes attract, like changes repel) would completely cancel out the chemical driving force acting on K+
30
What is the Nernst equation and what does each symbol represent?
• Nernst Equation: Ek= ((RT)/(ZF))* ln([K+]o/[K+]i)
o R- The Gas constant
o T- Temperature on the Kelvin Scale
o Z- Valence of Ion
o F- Faraday constant
o ln- natural logarithm
o [K+]o- molar concentration of potassium outside the cell
o [K+]i- molar concentration of potassium inside
o Ek- Nernst potential for potassium
31
What is the relationship between concentration and Ek
• The greater the concentration the more negative the Ek
32
What is the relationship between temperature and Ek
• The higher the temperature the more negative the Ek
33
What does Ek depend on?
• Ek depends on the actual concentration gradient for a given cell and the temperature
34
Describe what factors maintain/ determine the resting membrane potential
= Extremely slow and small amount of potassium ions flow out of cell, which leaves behind excess of large, negatively-charged organic anions (which can’t pass out of the neuron)- this is the main reason for negative resting potential
= Sodium/potassium pump which uses energy of ATP to actively transport sodium out of the cell while transporting potassium ions into the cell, which generates constant concentration gradient across membrane for each of these ions
= Relative permeability- At rest, the membrane is about 20-50 times more permeable to potassium ions than to sodium ions. This gives potassium the advantage and explains why the resting Vm is negative
35
What is the resting membrane potential of an inactive neuron?
-65 mV
36
Is the membrane polarised or depolarised at rest?
The membrane is polarised at rest- usually more negative inside the neuron than in the extracellular fluid
37
Describe how potassium travels between intracellular and extracellular fluid in a resting neuron and what determines its patterns and direction of movement
o Leakage channels in the membrane allow potassium ions to very slow cross from the inside of the neuron to the extracellular fluid- this is the chemical driving force for potassium ions
o Two opposite forces acting on potassium at resting membrane potential
Driving potassium from inside of cell to outside of cell: chemical concentration gradient (less potassium outside the cell than inside, so potassium inside the cell diffuses out)
Driving potassium to stay inside of cell: electrical driving force (potassium is a positive ion- if the membrane potential is negative because of organic anions, it will want to stay inside the cell- opposite forces attract)
38
How many sodium ions does the sodium/potassium pump transport for every potassium ion
o Transports 3 sodium ions out of the cell for ever 2 potassium ions in the cell
39
What is the sodium/potassium pump essential for?
o Sodium/potassium pump essential for chemical diving force
40
If the sodium/potassium pump is stopped by an inhibitor, what will happen?
o If the sodium/potassium pump is stopped by an inhibitor, the resting membrane potential will slowly become less negative over many minutes-> Hence, Sodium/potassium pump is not needed to directly polarise the membrane in the short term: it is more of a long-term effect
41
What is the Ek when the membrane of the neuron is at rest?
o The Ek when the membrane is at rest is about -75 mV
42
Why is the membrane potential never as negative as Nernst's potential for potassium?
o The diffusion of sodium ions into the neuron balances the diffusion of potassium ions into the extracellular fluid- this means that the membrane potential (Vm) is never as negative as Nernst’s potential for potassium (Ek)
43
What is the Ena for resting membrane?
For a resting membrane potential, ENA is about +55mV
44
What is the Goldman equation used for?
o Goldman equation takes into account relative permeability of the membrane to sodium vs potassium to calculate membrane potential
45
What are action potentials produced by?
• Action potentials are produced by rapid changes in the relative permeability of the membrane to sodium ions or other ions
46
How long are action potentials?
• Can last 2 milliseconds
47
What causes neuronal depolarisation?
• When membrane permeability to sodium ions suddenly increases, the rate of influx of sodium ions will instantly increase in direct proportion to the increase in permeability/conductance to sodium ions, which causes the membrane to depolarise
48
How is depolarisation initiated by?
• Depolarisation is initiated by opening of ligand-gated cation channels in the postsynaptic membrane of a chemical synapse
o This causes brief, local increase in the rate of influx of sodium ions and a brief rise in the membrane potential above its resting level (Excitatory postsynaptic potential)
o If the depolarisation reaches a certain threshold amplitude it initiates an action potential
49
What type of potentials are excitatory postsynaptic potentials?
Graded potentials
50
How does the action potential propagate along a motor neuron?
• The action potential then propagates rapidly among the myelinated motor neuron axon (about 100m/s) by saltatory propagation until it reaches the motor nerve terminal
51
What is saltatory propagation?
o Saltatory propagation- propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials
52
What gates are in voltage-gated sodium channels and how do they work together?
• Voltage-gated sodium channels have an activation gate and an inactivation gate, which both need to be open for sodium to pass through
53
Describe the role of voltage-gated sodium channels in action potentials and how they behave when an action potential is triggered
* The rising phase of an action potential results from the self-reinforcing opening of a population of voltage-gated sodium channels (VGSC)
* Activation gates of voltage-gated sodium channels quickly open in response to depolarisation of the membrane
* Increased influx of sodium ions causes neighbouring voltage gated sodium channels to also open (Hodgkin cycle)
* After the membrane has been depolarised for a short time (less than a millisecond), the inactivation gates of the same voltage gated sodium channels shut off the inward current of sodium ions
54
What is the Hodgkin cycle?
The Hodgkin cycle represents a positive feedback loop in neurons, where an initial membrane depolarization from the resting value (∼ −70 mV) to the threshold value (∼ −50 mV) leads to rapid depolarization of the membrane potential to approach the equilibrium potential for Na+
55
DEscribe the properties of the axonal voltage-gated potassium channel that complement the role of the sodium channel in creating action potentials
How do voltage-gated potassium channels behave when there is an action potential? What stages are they responsible for?
• Whilst voltage-gated potassium channels (VGKC) respond to depolarisation, their activation gates are slower to open than sodium ones
• As they open, potassium ions diffuse out of the cell at a faster rate and this rapidly moves the membrane potential from its peak value back towards Ek
• Inactivation of voltage gated sodium channels and opening of voltage gated potassium channels are responsible for the repolarisation phase of the action potential
• Because the voltage-gated potassium channels are slow to close their activation gates after the membrane is repolarised, after-hyperpolarisation (where membrane potential drops below resting membrane potential for a few milliseconds after repolarisation) occurs
o This is referred to as the period of reduced excitability
56
What kind of chemical synapse is a neuromuscular junction?
• Neuromuscular junction is an excitatory chemical synapse
57
Describe the steps in neuromuscular transmission (from motor axon to muscle fibre)
• Neuromuscular transmission (from motor axon to muscle fibre)
1. Depolarisation of the motor nerve terminal by the action potential causes the opening voltage gated calcium channels (VGCCs) in the presynaptic membrane
2. The voltage-gated calcium channels allow a brief pulse of calcium ions to diffuse from the extracellular fluid into the axon terminal, driving by a strong chemical driving force
3. Inside the axon terminal, calcium ions binds sensory proteins on synaptic vesicles that are docked on the inner face of the presynaptic membrane. This triggers exocytosis of acetylcholine contained within the synaptic vesicle into the synaptic cleft
4. The acetylcholine binds to acetylcholine receptors on the postsynaptic membrane
Acetylcholine receptors are ligand-gated cation channels
5. When the quantum of acetylcholine binds to the about 2000 acetylcholine receptors on the postsynaptic membrane, their cation channels open and sodium ions diffuse into the muscle fibre through the postsynaptic membrane
6. The endplate potential triggers a postsynaptic action potential that then propagates along the muscle fibre membrane, initiating muscle contraction
58
What is the endplate potential?
Endplate potential- Simultaneous release of many quanta of acetylcholine causing a large graded depolarization due to the sum of the many quantal depolarisations.
• Endplate potentials triggers the Hodgkin cycle in the muscle fibre
59
What is a quantum of acetylcholine?
• Quantum of acetylcholine- a vesicle load (or about 5,000 molecules) of acetylcholine
60
What is the miniature endplate potential?
• Miniature endplate potential- the brief opening of about 2000 acetylocholine receptor channels from one quanta of acetylocholine resulting in a small depolarisation
61
Describe how the contractile machinery of muscle fibre is organised and what are its components
o Contractile machinery of the muscle fibre is organised in a series of sarcomeres
Thick filaments of myosin
Thin filaments of actin
62
How is force generated in skeletal muscle fibres? What can prevent this?
o Force is generated when the head part of myosin binds to actin
o This is blocked most of the time by tropomyosin, which covers the binding sites on the actin filaments
63
Describe the process of excitation-contraction coupling in skeletal muscle fibres
o Postsynaptic action potential rapidly spreads depolarisation from the neuromuscular junction along the full length of the muscle fibre and deep into the transverse tubules where it activates a complex of proteins to trigger release of calcium ions from the sarcoplasmic reticulum
o When calcium ions are released by the sarcoplasmic reticulum into the cytoplasm, they bind troponin (located on actin filaments) reversibly
o This displaces tropomyosin, allowing the myosin heads to bind to actin and initiate the cross-bridge cycle that generates contraction force
The force is generated using energy stored in ATP
o An active transporter pump protein works continuously to pump calcium ions from the cytoplasm back into the sarcoplasmic reticulum, so as to end the contraction
64
Describe how action potentials produce sustained tetanic conctraction
* A single action potential causes just a brief twitch contraction
* However, muscle contraction usually involves a train of action potentials (10-200 Hz that causes successive releases of calcium from the sarcoplasmic reticulum, building the cytoplasmic calcium ion concentration
* This sustained rise in the cytoplasmic calcium concentration (half a second or more) produces a sustained tetanic contraction
65
What does the amount of force produced during a tetanic contraction depend on?
o The amount of force produced during a tetanic contraction depends on the cytoplasmic calcium concentration
66
In a neuron, what does cytoplasmic calcium concentration depend on?
Action potential frequency
67
Describe the relationship between frequency and tetanic contraction forces
o Hence, higher frequencies cause greater tetanic contraction forces, up to about 150 Hz
68
What is voltage in terms of membranes and what is it measured in?
• Voltage (E) – measured in Volts or mV- the balance of charge across the insulating membrane
69
What is current in terms of membranes and what is it measured in?
• Current (I)- measures in Amps- rate of movement of charge across membrane (A/cm2)
70
What is conductance in terms of membranes and what is it measured in?
• Conductance (G)- measured in Siemens- ease with which current can cross the membrane (A/V/cm2)
71
How does capitance work in terms of membranes and what is it measured in?
• Capitance- measured in Farads- Property of the membrane, which is a thin insulator with a bilayer. When there is a difference in charge across the membrane, there are stored charges on the membrane.
o In a resting membrane potential, negative charges cling to inside of membrane and positive charges cling to outside of membrane (opposite charges attract)
o A*sec/V/cm2
72
For a given depolarizing input current, do different types of neurons generative different or similar output patterns of action potentials?
Different
73
Describe how the current-clamp recording system works
* A microelectrode pushed through the peripheral membrane of the neuron in the cell soma allows changes in membrane potential to be recorded relative to a reference electrode in the surrounding fluid
* Often a controlled amount of electric current is injected into the cell
74
What is the independent variable in a current clamp-recording system
o Independent variable- injected current
| Depolarises membrane potential above resting membrane potential and makes excitatory postsynaptic potentials
75
What is the dependent variable in a current clamp-recording system
o Dependent variable- membrane potential
76
What is the purpose of the current-clamp recording system and how does it achieve this purpose?
* Current clamp: records Vm and tests excitability with a current stimulus
* Controlled injection of current can be used to test how excitable the neuron is and the properties of the neurons
77
What is an excitable neuron?
o Excitable neuron- one that requires relatively little injected depolarising current to trigger action potentials
78
What is the purpose of the voltage clamp and how does it achieve this purpose?
* Voltage clamp: holds membrane potential (Vm) constant so as to record the underlying currents
* Voltage clamp recordings are used to dissect out the different transmembrane currents and work out the properties of the conductances/ion channels that generate these currents during electrical signal in neurons
79
Who first used voltage clamps with neurons and why?
• Hodgkin-Huxley (1952)
| o First to use voltage clamp to describe components responsible for membrane potential changes
80
What are the components of the voltage clamp and their purposes, as well as how they work with each other
o Pair of voltage electrodes and amplifier
First electrode- goes through the membrane and records membrane potential inside cytoplasm of neuron
Second electrode- monitors membrane potential of surrounding fluid
Amplifier- constantly monitors and measures membrane potential
o Current carrying electrodes connected to feedback amplifier
Feedback amplifier makes continuous automatic corrections to ensure that the membrane potential is held essentially constant at the command voltage
• When desired membrane potential is measured by membrane potential amplifier, it sends a signal to the feedback amplifier to stop feeding current
One current carrying electrode used to inject current into cell cytoplasm via command of feedback amplifier
The other one is in the extracellular fluid
o Command device- where the operator commands changes in membrane potential
81
What is the independent variable in a voltage clamp experiment?
• Independent variable- membrane potential
82
What is the dependent variable in a voltage clamp experiment?
• Dependent variable- transmembrane current (Im)
83
If looking at current clamp or voltage clamp results, what does a downward deflection on the graph indicate?
o Inward current- downward deflection on graph- most likely due to sodium
84
If looking at current clamp or voltage clamp results, what does an upward deflection on the graph indicate?
o Outward current- upward deflection on graph- most likely due to potassium
85
In a voltage clamp experiment, after the operator has commanded a substantial rise of membrane potential, what will be able to be seen and what will be the cause of these results?
o A very brief outward capacitance current (Ic), representing release of some of the stored ionic charge that was clinging to the axon membrane due to change in membrane potential which changes electrical driving force
o Capacitance current is then quickly dissipated so that we can see an increased steady-state current through the leakage channels due to a greater driving force on potassium ions
o Inward current gets greater and greater for a few milliseconds
Due to slow inward sodium current that normally drives the rising phase of action potential
• Inward sodium current slower than usual due to its low permeability
o Current reverses direction, becoming a net outward current
Slow-onset, outward potassium current that normally drives repolarization and after-hyperpolarization
86
What two factors does the magnitude of inward sodium current recorded with voltage clamp depend on?
• The driving force action on sodium ions
o Depends on difference between membrane potential and Nernst potential for sodium ions
o Permeability of the membrane for sodium ions depends on the number and permeability of sodium permeable channels open at the time (sodium conductance gNA)
87
Describe the equation to calculate inward sodium current and what each variable means
```
• Inward sodium current: INA=gNA(Vm-ENA)
o INA- Inward sodium current
o gNA- sodium conductance
o Vm- membrane potential
o ENA- Nernst potential for sodium
```
88
What is excitability?
• Excitability- The ability of certain cells to sense environmental changes (stimuli) and to respond to them with a change in membrane potential
89
What is membrane permeability?
• Membrane permeability- A measure of how easily ions or molecuels fflow across a membrane
90
What is membrane conductance?
• Membrane conductance- A measure of how easily charges flow across the neuron membrane
91
What is capacitance?
• Capacitance- Ratio of the change in electric charge of a system to the corresponding change in its electric potential
92
How does the motor neuron become more excitable when an animal undergoes the transition from sleep to active wakefulness?
• As an animal undergoes the transition from sleep to active wakefulness its motor neurons become more active so that they again start to activate the relaxed muscles
• Descending monoaminergic axons (noradrenaline and serotonin) from the brainstem branch to provide a very diffuse input to motor neurons throughout the ventral spinal cord
o Serotonin and noradrenalin are thought to act via G-protein coupled receptors as neuromodulators to increase the excitability of the motor neurons as animals wake up
• The diffuse monoaminergic input lowers threshold activates L-type calcium channels to generate sustained inward (depolarising) currents that persist long after the synaptic depolarisations finish
• The monoaminergic-driven persistent inwards currents are not enough on their own to reach threshold but they make motor neuron more excitable
93
Do antagonist muscles work against or with each other to control the angle of a joint?
Against
94
What sensory information do the muscle spindle and Ia afferent provide?
o Muscle spindle and Ia afferent provide sensory information about the changing length of the muscle
95
Describe how monosynaptic Ia afferent EPSP generation occurs
* The Ia afferent forms a neural circuit with the homonymous alpha-motor neurons which provides rapid feedback
* Any increase in the length of the muscle generates a receptor potential in the Ia afferent muscle spindle endings within a few milliseconds
* This graded depolarization is translated into a train of action potentials (spikes) at the trigger zone where the voltage-gated sodium channels are most concentrated
* The action potentials propagate by saltatory conduction along the myelinated Ia fibres until they reach the excitatory glutamatergic nerve terminals on motor neurons of the homonymous and synergist muscles
* Glutamate released from the Ia afferent terminal activates two kinds of ionotropic glutamate receptors in the postsynaptic membrane of the motor neuron
* Together, the currents generated by AMPA and NMDA receptor cation channels add together to generate glutamatergic EPSPs normally found in motor neurons
96
What is the relationship between increase in the length of the muscle (muscle stretch) and the frequency of action potentials? How is this detected?
o Stretch receptors on muscle spindle can detect intensity of stretch
o As stretch becomes more intense, the receptor potential would be bigger in magnitude and hence a higher frequency of action potentials would be created
97
What is the relationship between receptor potential depolarization and frequency of action potentials generated?
o The greater the receptor potential depolarization, the greater the frequency of action potentials generated (frequency code)
98
What does the amount of glutamate released by the Ia fibres after action potential depend on? Describe the relationship between those two factors.
o The amount of glutamate released by these nerve terminals depends upon the frequency of action potentials in a train because this determines the amount of calcium that enters the nerve terminal to trigger vesicle exocytosis
The higher the action potential frequency (and the more intense the muscle stretch), the more glutamate released
99
What is the relationship between amount of glutamate released and amplitude of EPSP in the postsynaptic motor neuron?
o The more glutamate released, the greater the amplitude of the ESP in the postsynaptic motor neuron
100
Describe what occurs at a glutamate junction when the membrane depolarises.
When membrane depolarises, it opens voltage gated calcium channels
Calcium comes into the neuron and triggers exocytosis of glutamate vesicles
Glutamate crosses synaptic cleft and binds to glutamate receptors, which triggers EPSP
Glutamate removed from synaptic cleft by active transporters EAAT1/EAAT2 on neighbouring astrocytes or by EAAT3 on the neuron membrane
Astrocyte converts glutamate to glutamine by glutamine synthetase
Through glutamine transporters, glutamine is pumped back into the neuron cell and converted to glutamate by glutaminase action
101
What are the two types of ionotropic glutamate receptors in the postsynaptic membrane of the motor neuron? Describe them
o AMPA-type glutamate receptors and NMDA receptors, which are both glutamate-gated cation channels which are permeable to both sodium and potassium
102
How do AMPA receptors work in response to glutamate?
o AMPA receptors open rapidly whenever glutamate binds to them and opens their channel gate, allowing potassium and sodium to diffuse across the membrane and they then produce the initial peak inward current at the start of the excitatory postsynaptic current
A lot more sodium goes in than potassium goes out through this channel due to the strong inward electrical driving force
103
How do NMDA receptors work in response to glutamate? What can they be blocked by?
o NMDA receptor channels only open when glutamate binds and the membrane is depolarised: they hence contribute to the late current
At polarised potentials NMDA receptor channels are blocked by a magnesium ion
NDMA receptors can be blocked by APV
104
What ionotropic glutamate channel is responsible for the initial start of the excitatory postsynaptic current produced after monosynaptic Ia afferent EPSP generation?
AMPA receptor
105
What ionotropic glutamate channel is responsible for the late excitatory postsynaptic current produced after monosynaptic Ia afferent EPSP generation?
NMDA receptor
106
How does Ia fibres generate the stretch reflex (in terms of action potentials)?
* During a stretch reflex the homonymous motor neuron will receive simultaneous glutamatergic synaptic inputs from multiple Ia afferents
* The inward currents generated at these many synapses on the dendritic tree of the motor neuron will summate in the neuron soma
* If this summed depolarization is sufficient to reach threshold at the trigger zone (beginning of axon) it will generate a train of action potentials for as long as the membrane potential remains above threshold
* The higher the membrane potential goes above threshold the higher the frequency of spikes in the resultant train
* This is what produces the stretch reflex contraction
107
What is the role of inhibitory neurons and how are Ia inhibitory interneurons innervated/ what neurotransmitter do they release and where?
* One branch of the Ia afferent innervates the Ia inhibitory interneuron, which releases glycine at inhibitory synapses on the motor neurons of antagonist muscles
* Inhibitory interneurons play a vital role in controlling information processing throughout the CNS
108
What is the most common inhibitory neurotransmitter in the brain and on what receptors does it act?
• In the brain, GABA (gamma amino butyric acid) is the most common inhibitory neurotransmitter and it acts on postsynaptic GABAA receptors
109
What is the most important inhibitory neurotransmitter in the spinal cord?
• In the spinal cord, glycine is another important inhibitory neurotransmitter, particularly for inhibitory inputs to motor neurons
110
What types of channels are GABAa receptors and glycine receptors and how do they work?
• GABAA receptors and glycine receptors are both ligand-gated chloride channels
o When chloride channels open, they diffuse into the cell by chemical driving force and reduce input resistance (make cell more leaky)
111
What is the Nernst potential for chloride?
-70mV
112
What inputs do motor neurons receive?
• Whilst motor neurons receive constant excitatory inputs from their many glutamatergic synaptic inputs, they also receive continual inhibitory synaptic inputs- di-synaptic input
113
What is a Inhibitory postsynaptic potential?
Inhibitory Postsynaptic Potential (IPSP)- membrane is hyperpolarised for a little while
• In IPSP, outward current produces hyperpolarisation
Inhibitory Postsynaptic Potential (IPSP)- membrane is hyperpolarised for a little while
• In IPSP, outward current produces hyperpolarisation
114
What is the effect when a postsynaptic glycine receptor chloride channel opens during inhibitory synaptic transmission
o Opening of postsynaptic glycine receptor chloride channels during inhibitory synaptic transmission tends to hold membrane potential down near resting state
115
What is the role of inhibitory synaptic activity on motor neurons?
o Hence, inhibitory synaptic activity on motor neurons tends to suppress motor neuron firing and relaxes the tone in the muscles they control
116
What is neuronal integration?
• Neuronal integration- The combining of excitatory and inhibitory synaptic inputs within a neuron
117
What is a functional set?
• Functional set- the adaptation of reflexes to particular tasks
118
How is a functional set achieved?
• Descending fibres from the brainstem and motor cortex act via excitatory and inhibitory synapses and neuromodulation to adapt the spinal reflex circuits to achieve the functional set
119
What is the effect of descending inhibitory inputs to the Ia inhibitory interneuron? Why is this done?
o Descending inhibitory inputs to the Ia inhibitory interneuron have the effect of suppressing the stretch reflex
o The effect of this is to maintain tone in the antagonist muscles and stiffen the joint, when this is desirable
120
What is the effect of descending excitatory inputs to the Ia inhibitory interneuron?
o Descending excitatory inputs to the Ia inhibitory interneuron can enhance the reflex when appropriate to motor task
121
What is a renshaw cell?
a class inhibitory interneuron in the ventral and lateral spinal cord
122
What are the outputs and inputs to the Renshaw cell? What is the purpose of these inputs/outputs?
o Receives excitatory cholinergic synapses from collateral branches of the motor neuron axon
Whenever a motor neuron fires these collateral branches produce inhibitory feedback to the motor neuron
o Homonymous and synergist motor neurons also receive inhibitory inputs from the Renshaw cell
o This feedback inhibition is thought to help stabilise firing of the motor neurons
o Other collateral branches of the Renshaw cells provide inhibitory input to the Ia inhibitory interneurons of the antagonist motor neurons
By inhibiting the Ia inhibitory interneuron the Renshaw cell may moderate reciprocal inhibition
o Renshaw cells receive descending inhibitory and excitatory synaptic inputs from motor centres in the brain and brainstem
o These may also help adjust the functional set for a given motor task
123
What information does the golgi tendon organ and Ib afferent provide?
• The Golgi tendon organ and Ib afferent provides information about the amount of tension in the tendon
124
Which has a greater diameter? Ib afferent axons or Ia fibres?
• The Ib afferent axons that arise from Golgi tendon organs are slightly smaller diameter than the Ia fibres but they still propagate their action potentials very rapidly
125
What is the relationship between Ib afferents and Ib inhibitory interneurons?
• The Ib afferents provide excitatory synaptic inputs to the Ib inhibitory interneurons
o Cutaneous afferents and joint receptors also provide inputs to the Ib inhibitory interneurons
Example of neuronal convergence
126
What does Ib afferent activity drive the motor neuron to do when an animal is in resting state vs when the animal is walking?
* When an animal is in a resting state the Ib afferent activity drives the Ib inhibitory interneuron to hyperpolarise the resting membrane potential in the homonymous motor neuron
* In contrast, when the animal is walking, activity in the same Ib afferents has the opposite effect- they instead act via an excitatory interneuron to excite the motor neurons
127
What is hyper-reflexivity and why would it occur?
* Hyper-reflexivity: Overactive or overresponsive reflexes
| * Due to loss of inhibitory modulation from descending pathways
128
How does the muscle stretch reflex occur and what is the principle behind it?
• Joints are controlled by two opposing sets of muscles, extensors and flexors, which must work in synchrony.
• Thus, when a muscle spindle is stretched and the stretch reflex is activated, the opposing muscle group must be inhibited to prevent it from working against the resulting contraction of the homonymous muscle.
• This inhibition is accomplished by an inhibitory interneuron in the spinal cord.
• The Ia afferent of the muscle spindle bifurcates in the spinal cord.
o One branch innervates the alpha motor neuron that causes the homonymous muscle to contract, producing the behavioral reflex.
o The other branch innervates the Ia inhibitory interneuron, which in turn innervates the alpha motor neuron that synapses onto the opposing muscle.
• Because the interneuron is inhibitory, it prevents the opposing alpha motor neuron from firing, thereby reducing the contraction of the opposing muscle.
• Without this reciprocal inhibition, both groups of muscles might contract simultaneously and work against each other.
129
What is the purpose of the Renshaw cell?
* This interneuron innervates and inhibits the very same motor neuron that caused it to fire.
* Thus, a motor neuron regulates its own activity by inhibiting itself when it fires.
* This negative feedback loop is thought to stabilize the firing rate of motor neurons.
130
How can the reflex response be regulated?
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• Excitability of the alpha motor neuron
• Excitability of interneurons
• Modulation of transmitter release from afferent terminals
o Pre-synaptic level
Presynaptic inhibition
Presynaptic facilitation
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131
How does excitability of the alpha motor neuron regulate reflex response?
o Descending tonic excitatory inputs can increase excitability- can increase membrane potential closer to the threshold level for firing action potentials
Doesn’t fire action potentials on its own though
132
Describe how presynaptic inhibition regulates the reflex response
* Neurotransmitters/ neuromodulators released by a third cell to inhibit inward calcium current/calcium channels in the presynaptic neuron in order to reduce transmitter released
* Reduces postsynaptic potential
* Works through G-protein coupled receptor signals to act on ion channels/calcium channels in the membrane to suppress their activity
* May hold activity of circuit down for seconds or minutes depending on the functional set
133
Describe how presynaptic facilitation regulates the reflex response
* Increases post-synaptic response to pre-synaptic signal
* Third cell releases neuromodulator to change length of repolarisation phase- instead of action potential in the nerve terminal being very brief, voltage-gated potassium channels are inhibited in nerve terminal so it takes longer for membrane to repolarise
* While it is still depolarised, calcium channels remain open for longer and more calcium enters the nerve terminal, more synaptic vesicles are released, prolongs and enhances excitatory postsynaptic potential
134
What iss the pupose and functioning of a servomotor. What can the servomotor concept apply to?
* Designed with feedback so that it can move to a particular position and then hold that position
* Servomotor generates torque, which produces angular velocity until get to right position. Then there is feedback to servomotor that then controls the torque to hold the position
* Motor tasks require active control of joint angles- servomotor concept can apply to joint control
135
Describe alpha motor neurons compared to gamma motor neurons in terms of:
- Number of motor neurons
- Synapse formation
- What it controls
- Function
Alpha motor neurons-
- About 80% of motor neurons
- Form synapses on extrafusal muscle fibres
- Control motor units
- Directly control muscle tension
Gamma motor neurons
- Minority of motor neurons (10-20%)
- Form synapses on intrafusal muscle fibres that comprise muscle spindles
- Set tone of spindle
- Enhance the gain and/or steady-state firing of the Ia afferent fibres
136
Describe how desired position of limb is achieved from an undesired limb position
• Descending inputs (direct and via interneurons)-> coactivation of alpha motor neurons and gamma motor neurons-> intrafusal muscle fibres-> muscle spindle tension -> Ia afferent firing rate-> servomotor cycle starts
o Servomotor cycle: Ia afferent firing rate-> alpha motor neurons-> torque (extrafusal muscle fibres contraction force)-> velocity (rate of rotation about the joint)-> position of limb (desired joint angle-> circularises back to Ia afferent firing rate
• If desired position of limb is achieved, Ia afferent firing rate will reach steady level
137
What type of read-out and signal component does stretch produce in afferents?
• Stretch produces a graded static read-out and a dynamic signal component in afferents
138
How does an increase in the firing rate of the gamma motor neuron influence muscle contraction?
* When gamma motor neuron is active, causes contraction of intrafusal muscle fibres, increasing tension on muscle spindle (with Ia receptor endings wrapped around them), which causes Ia afferents to fire more frequently
* By activating gamma motor neurons, can indirectly increase firing rate of Ia afferents and alpha motor neurons -> drive contraction indirectly by gamma motor neurons or directly by alpha motor neurons
139
Describe the structure of the muscle spindle and the function of the neurons in the structure/ how these structures work together
• Intrafusal muscle fibres run side by side in amongst the extrafusal muscle fibres in the muscle
• In the middle of muscle is muscle spindle which has capsule wrapped around it
o Innervated by Ia afferent receptor endings wrapped like spiral/spring- if muscle fibres stretch, intrafusal fibres stretch, puts tension on endings, causes opening of stretch activated ions channels, allows sodium to diffuse in, depolarise and triggers action potentials in Ia afferents
o Innervated by gamma motor neurons
Form neuromuscular junctions on intrafusal muscle fibres
Affect tension in intrafusal muscle fibres and hence affect tension in Ia afferent receptor endings
140
Compare Type Ia and type II afferent fibres in terms of:
- Myelination
- What affects firing rate
- Function
- Diameter
Type Ia (primary);
- Largest myelinated axons
- Firing rate affected by both muscle stretch and rate of change in length (signals start and stop of movements to spinal cord)
- Responsiveness controlled by gamma-motor neurons
- Rapid signalling vital for reflexes
- Large diameter
Type II (secondary):
- Second largest myelinated axons
- Firing rate proportional to muscle length
- Information about joint angle/limb position
- Provides information on how much muscle has stretched
- Small diameter
141
Describe the feedback loop and its components when muscle length has deviated from its desired position?
o Motor command wants to hold muscle steady
o Load on muscle makes muscle length
o Increased muscle length is sensed by Ia receptors due to increased tension in muscle spindle
Gamma motor neurons increase feedback in spindle to any change in stretch
o Causes increased firing in Ia afferents which causes increases excitatory tone in alpha motor neuron- alpha motor neuron is likely to fire at higher rate and increases extrafusal muscle fibre tension
o Causes more torque/force to be produced in extrafusal muscle fibres, which produces force which opposes the lengthening and brings position of limb back to where it should have been
o Once it shortens back to where it should be, there is relief of spindle tension
o Firing rate of spindle and Ia afferents drop down, activation of alpha motor neurons drops down and there is less extrafusal muscle fibre tension
142
Why do we need gamma motor neurons?
* As the muscle shortens the tension on the spindle receptors would be reduced and feedback function of Ia afferents lost
* Activity of gamma motor neurons eliminates slack in the spindle so the receptors can continue to monitor small changes in length that correspond moves in joint angle
* Need to maintain tension in muscle spindle
143
How does gamma motorneurons regulate Ia muscle spindle?
• Gamma motorneurons regulate Ia muscle spindle afferent firing rate by selective contraction of intrafusal muscle fibres
144
Where does gamma motor neurons regulate tension in?
• Gamma motor neurons regulate tension in the muscle spindle
145
What does activation of static gamma fibres increase?
• Activation of static gamma fibres increases tonic output of Ia afferents
146
What does activation of gamma dynamic fibres increase?
• Activation of gamma dynamic fibres increases the gain: the amplitude of the response to stretch
147
What determines the excitatory tone in the alpha motorneurons?
• Firing rate of Ia afferents, in turn, determines the excitatory tone in the alpha-motorneurons
148
What are the two types of gamma motor neurons?
* Static gamma motor neurons
| * Dynamic gamma motor neurons
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What do static gamma motor neurons innervate?
innervates static nuclear bag fibres and nuclear chain fibres in intrafusal muscle fibres
150
What kinds of receptor endings do the muscle fibres innervated by static gamma motor neurons haveand what type of information do they provide?
o These groups of muscle fibres have receptor endings from type II afferents (which provide info about limb position- length related increased) and receptor endings from type Ia afferents (receiving inputs about muscle stretch and sudden changes)
Two types of information from Ia afferents-
• Movement is occurring/stopping (time essential information)
• Information related to how much muscle is stretched
Two types of information from Ia afferents-
• Movement is occurring/stopping (time essential information)
• Information related to how much muscle is stretched
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What is the role of static gamma motor neurons?
o Accentuates signalling of length of muscle
| o Activity in static gamma motor neurons increases background (tonic) firing rate of afferents
152
What fibres do dynamic gamma motor neurons innervate?
• Dynamic gamma motor neurons- innervates dynamic nuclear bag fibres in intrafusal muscle fibres
153
Describe what receptor endings muscle fibres innervated by dynamic motor neurons have
o This group of muscle fibres have receptor endings from type Ia afferents only (receiving inputs about muscle stretch and on/off signals)
154
What is the role of dynamic gamma motor neurons?
o Accentuates signalling about beginning and end of any movement- timing importance
o Activity in dynamic gamma motor neurons increases gain the in the dynamic response- the acceleration and deceleration signals (start and finish of a movement)
155
Describe the firing of dynamic and static gamma motor neurons for a cat resting
o No firing of dynamic gamma motor neurons
| o No firing of static gamma motor neurons
156
Describe the firing of dynamic and static gamma motor neurons for a cat sitting
o No firing of dynamic gamma motor neurons
| o Small firing of static gamma motor neurons
157
Describe the firing of dynamic and static gamma motor neurons for a cat standing
o No firing of dynamic gamma motor neurons
| o Small firing of static gamma motor neurons
158
Describe the firing of dynamic and static gamma motor neurons for a cat slow walking
o No firing of dynamic gamma motor neurons
| o Moderate firing of static gamma motor neurons
159
Describe the firing of dynamic and static gamma motor neurons for a cat fast walking
o Small firing of dynamic gamma motor neurons
| o Large firing of static gamma motor neurons
160
Describe the firing of dynamic and static gamma motor neurons for a cat imposed movement
o Large firing of dynamic gamma motor neurons
| o Small firing of static gamma motor neurons
161
Describe the firing of dynamic and static gamma motor neurons for a cat paw shaking
o Large firing of dynamic gamma motor neurons
| o Small firing of static gamma motor neurons
162
Describe the firing of dynamic and static gamma motor neurons for a cat beam walking
o Large firing of dynamic gamma motor neurons
| o Large firing of static gamma motor neurons
163
Why is there differential firing of dynamic vs static gamma motor neurons in different cat behaviours?
* Sitting, standing- need to know small amount about limb position
* Imposed movement, paw shakes, beam walking- need to know a lot of information about limb movement
* The selective activation of the two types of gamma motor neurons allow the cat/human to adjust to the particular behavioural task it is trying to achieve and to optimise the kind of information that’s coming back to what’s needed to achieve that task
164
How do you set up for a measurement of the H reflex?
o Put person on back with ankles off the bed so that calf muscle is relaxed
o Put electrodes over soleus muscle to detect action potentials in muscle, and put a stimulus electrode over nerve that innervates soleus muscle so can apply pulses to activate action potential in nerve to cause contraction in soleus muscle
165
What is the principle behind measuring the H reflex? What is that measurement detected as and why?
• Innervating electrode can stimulate action potentials in both directions due to its placement over two different axons (one afferent, one efferent)
o When stimulus is applied on efferent axon, it causes contraction of muscle- detected as the M wave
o When stimulus is applied on afferent axon, produces action potential that goes up the Ia afferent and back down the alpha motor neuron- detected as the H wave
H wave is delayed as signals have to travel further compared to M wave signal
166
How do you properly measure an H wave?
• To measure H wave
o Start with low stimulus voltage- this will activate biggest diameter fibres (Ia afferents) first
o As turn up stimulus voltage, start to see M waves: motor axons are smaller in diameter than Ia afferents and so require higher stimulus voltage to reach threshold
o As stimulus voltage increases, M wave impulse increases
167
What kind of information does the Hoffman reflex provide about central neuronal circuits in an individual?
• Test for abnormalities in stretch reflex circuit
168
Describe the four phases of limb movement in locomotion and different muscle groups activated to achieve these phases
• Swing phase- flexors most active
o Flexion (F) phase
Hip, knee and ankle joints all flex simultaneously to lift the foot clear of the ground and swing it forward
o E1 phase
Knee and ankle begin to extend, in preparation to contact the ground, but the hip continues to flex
• Stance phase- extensors most active
o E2 phase-
Foot first touches the ground and the extensor muscle are activated even as they stretch to absorb the weight of the body (eccentric muscle contraction)
o E3 phase- power stroke
Strong activation of the extensors at all three joints propels the body forward
169
What is the role of the central pattern generator?
• The pattern generator for locomotion in the spinal segments can, when activated by descending signals, generate back and forth walking movements of the legs and can respond to descending signals to speed up or slow down the pace of stepping. Descending inputs can also modify the pre-programmed stepping cycle when needed.
170
What are the components to generating a motor pattern? What feeds into each component?
• Rhythm generator (half-centre hypothesis)-> patterning network-> motor neurons-> motor pattern
o Afferent signals feedback on patterning network
o Patterning network influenced by descending signals and drugs
171
Describe the mechanism of how feedback from afferent and lower motor neurons can cause a half centre neuron to switch to its antagonist half centre neuron
• Circuit: afferent feedback
o Lot of firing in Ib fibre due to tension on muscle as it actively contracts
o This innervates excitatory half centre, which further maintains corresponding motor neuron excitation
o As come to end of stance phase and muscle shortens (1b firing drops off), positive feedback cycle starts to lessen
o Hence the antagonist half centre can take over and silence the half centre
172
What is critical in determining walking pace?
• What controls beginning of swing phase is critical in determining pace
173
What can trigger the end of the stance phase during walking?
• Flexor afferent feedback can trigger the end of stance phase
174
What can prolong the stance phase during walking?
• Excitatory Ia and Ib afferent feedback from active ankle extensors can prolong stance phase
175
Describe how excitatory Ia and Ib afferent feedback from active ankle extensors can prolong stance phase
o Ia afferents fire at high frequency while the ankle extensor muscles are still working (while it is stretched)
o Ib afferents in the tendons of ankle extensor muscles fire at high frequency so long as there is tension on the muscle (while it is working to push the body forward). During locomotion the Ib afferent activity excites the extensor motor neurons
o Output of class I (Ia and Ib) afferents from ankle extensors drops off at the end of the power stroke
o 1a fibres and 1b fibres provide feedback from extensors to half centre- positive feedback cycle
176
Describe how pace can be controlled by changing the timing of the switch to swing
o Increased Ia firing from stretched hip flexor muscles (when hip is fully extended) help trigger the transition to swing
o Excitatory Ia and Ib output from the extensors sustains stance until load is relieved when the foot is trailing and firing drops off
o Transition likely mediated by half-centre circuits
177
Describe the essential factors in walking
* Alternate activation of flexors then extensors
* Coordinate left and right legs (180 degrees out of phase)
* Generate a rhythm (pace)
* Coordinate muscles at ankle, knee and hip joints
* Adjust the rhythm (pace) according to terrain and descending commands
178
How do spinal segments generate a rhythm walking pace? What neurons are used?
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o Spinal segments can produce an alternated rhythmic burst firing of flexor and extensor motor neurons
o A class of excitatory interneurons has been identified in relevant parts of the spinal cord by their expression of distinct transcription factor genes (Hb9-positive neurons)- may be beat generator for locomotion
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179
What properties of Hb9 positive neurons suggest that they may be part of a pattern generating network?
* Hb9 neuron fires right at the beginning of the burst
* Display burst firing in phase with the burst firing of flexor motor neurons (L1-L3 ventral root axons during the swing phase)
* Burst activity patterns can still be elicited in Hb9 neuron, even when excitatory and inhibitory inputs to them are blocked. This shows that these neurons are independent beat generators
* Hb9 positive neurons are electrically coupled, coordinating their firing as a group
180
What is the half-centre hypothesis?
• Half-centre hypothesis: two opposing groups of interneurons (half-centres) mutually inhibit each other. The outputs of each provides excitation to drive flexor and extensor motor neurons respectively
o When extensors are activated, flexors are silent
o When flexors are activated, extensors are silent
181
How do half centre neurons work in tandem with their antagonist?
• Half centre neurons fire in a burst- motor neuron receiving that input mirrors that burst
o Half-centre neurons also innervate inhibitory neuron which inhibits opposing half centre neuron-> shuts down antagonist half centre and hence shuts off antagonist motor neuron
o Positive feedback cycle from motor neuron receiving excitatory input allows flexor reflex afferent to fire again until something happens e.g. activation of other antagonist flexor reflex afferent
o Makes sure that antagonists do not work against each other
182
Where are half-centre neurons located?
• Between dorsal and ventral horns of spinal cord
183
What is the role of half centre neurons? Do they do this alone?
• Half centres may help coordinate the alternating movements of the two legs during locomotion with the help of reflex afferents
o Activation of flexor reflex afferents during normal walking might trigger the swing phase and that would silence extensors
o Feedback from contralateral flexor reflex afferents would active the extensor half centre and silence the flexor half centre to activate stance phase
184
How can alternating burst activation of flexor and extensor motor neurons be triggered?
• Alternating burst activation of flexor and extensor motor neurons can be triggered by sensory afferent stimulation
185
In spinal transection cats treated with L-DOPA to increase excitability, what happened when there was brief stimulation of flexor reflex afferents?
• In spinal cats treated with L-DOPA (precursor of dopamine and noradrenaline) to increase excitability, brief stimulation flexor reflex afferents (FRA) triggered sustained bursts of activity in either flexor or extensor motor neurons depending on whether ipsi-contra-lateral nerve stimulated
186
What are flexor reflex afferents?
o Flexor reflex afferents-
| High threshold afferents (small diameter) sensory fibres that come from receptors in skin and muscles
187
What happens when flexor reflex afferents are stimulated?
• When stimulate these afferents, trigger activation of burst firing from motor neurons
o Flexor reflex afferent excitation-> excites half-centre neuron-> excites the ipsilateral neuron
188
What are spinal cats models of? How are they made? Why are they made? How is their data recorded?
• Spinal preparation- transect spinal cord in cat
o Segments of spinal cord that activated hind limbs separated from rest of CNS
o To see whether or not the brainstem/brain was needed to generate the stepping motion
o Cat wired up for electromyography so recordings can be made from its extensor muscles and its flexor muscles
Can see activity of muscles which are generating movement in the leg
189
What are observations that were made from observing spinal transection in cats?
Can increase or reduce its pace to match changes in the speed of the treadmill
Afferent feedback from the leg can adjust pace of the pattern generator in the spinal segments
Stance phase is shortened or lengthened to change pace
190
What happens after a cat has had a spinal transection (immediate effects)
Spinal transection in cat eliminates descending pathways
| Initial (acute) immobility after spinal transection
191
In spinal transection cats, how can rhythmic walking motion be re-established?
Rhythmic walking motion could be re-established by applying a tonic electrical stimulation to the cut cord
192
How can pace of walking be increased in cats with a spinal cord transection?
Pace of walking could b increased by increasing the electrical stimulus to the cut end of the cord
• Signal coming from the brain to coordinate walking not necessary- but may be necessary to switch behaviour on and off, as well as pace for behaviour
193
What initiated treadmill walking in cats with a spinal cord transection?
Mechanically moving the limbs (moving hip forward and backward) also initiated treadmill walking
194
What is the role of afferent cord during walking?
* Afferent cord role- provide tonic excitatory input to neurons to keep them excitable
* Afferents confer excitatory tone to motor neurons
* Proprioceptor afferents normally act to modify stepping
195
What happens if the cord is de-afferented in the spinal transection cat?
o Role of de-afferented cord (cutting of the dorsal roots through which limb afferents pass)- motor neurons left intact
Eliminates sensory afferent feedback to the spinal cord
Reduced tonic excitatory synaptic input to the motor neuron making the motor neuron less excitable
196
Do you need afferent feedback for rhythmic walking movements?
However rhythmic walking movement could be produced even in the absence of sensory feedback
197
Why is afferent feedback not necessarily needed for rhythmic walking movements?
• With right kind of stimulate drugs (excitatory drugs of monoaminergic type) and stimulation, can lift excitability of motor neuron and turn on motor behaviour
198
What did Brown et al. 1911 find in his transected spinal cord cat study?
Stepping required neither sensory feedback via dorsal roots nor supraspinal descending inputs to generate rhythm
• Brown et al. 1911
199
Where is rhythmicity of stepping generated?
Rhythmicity of stepping must be generated within the spinal segments (pattern generators)
200
How are spinal pattern generating circuits activated or suppressed?
These spinal pattern generating circuits can be activated or suppressed according to the level/frequency of descending tonic signals
201
What are decerebrate cat studies done and what can be learned from them?
• Decerebrate cat studies- transect through brainstem:
o Separate different parts of brainstem from spinal cord to see how that affects the activation of different patterns of locomotion
202
Describe an experiment that was done to understand the coordination between the hip joint and knee joint, including:
- Model
- Mode of treatment
- Result
- Conclusion
Immobilised, decerebrate cat
• Curare to block neuromuscular transmission and prevent muscle contraction
• Muscle can be mechanically stretched to activate stretch receptors, tendon and joint receptors in any pattern desired
• A servomotor is extending and flexing the hip joint repeatedly to mimic walking- stretches stretch receptors in hip flexor muscles
• Each time there is mechanical extension of the hip, causes alternating activation of knee flexor and extensor motor neurons
o Knee extensor motor neurons stop firing and knee flexor motor neurons begin firing when the hip flexor is pulled to the end of its stretch- entrainment of the transition to swing phase
• Suggests that hip joint allows control and coordination of other joints in hind limb- information coming from stretch receptors in the hip flexor are able to transition from stance phase to swing phase at the knee level
203
Describe how a treadmill walking decerebrate cat experiment increased understanding of the relationship between knee and hip flexion/extension during walking. Include:
- Method
- Result
Move hip backward and forward in normal walking behaviour
Record knee flexors and extensors
During knee extensor, stretch hip flexor (sudden increase on stretch in hip flexor)
• Observation: knee extensor motor neuron firing suddenly shuts off and get a premature transition to knee flexor activator
• Change of activity at hip level results in change of behaviour at knee level
Motor neurons at different levels are coordinated and are using information of extension at the hip level to coordinate transition from stance phase to swing phase
204
Describe an experiment made to test the influence of class Ib afferent output from ankle extensor muscle
- Method
- Result
Stimulate extensor Ib afferents
• The extensor firing extends hugely for as long as there is maintenance of Ib afferents
• Continual firing of Ib afferents that maintains the activation of the extensor half centres
At end of stance phase, body motion forward is lifting weight off ankle so tension on the golgi tendon organs is easing off-firing rate of Ib afferents would drop
205
What is thought to determine the length of the stance phase?
Feedback from Ib afferents is thought to determine the length of the stance phase
