A Simple Reflex Loop

Introduction

• In previous units, you have studied different mechanosensory neurons, and muscles receiving inputs from sensory neurons or from motor neurons.

• These are examples of feedforward systems, i.e., systems in which activation flows in one direction.

• However, the nervous system is intimately coupled to sensory inputs and motor outputs through short and long feedback loops.

• To begin to understand this coupling, we will study one of the simplest feedback loops, a stretch reflex, that is, the ability of a muscle to respond to brief stretch by shortening back to its original length.

• Thus, we will first describe proprioceptors (the word means self sensors), structures that allow the body to sense its own position and the forces that it is generating, and then we will describe the stretch reflex.

• You will then have the opportunity to explore a stretch reflex through the analysis of a simulation.

Proprioceptors

• Proprioceptors are structures within muscles and joints that provide sensory feedback about joint angle, length and force of a muscle.

• Within muscles, the key structures are muscle spindles, which provide information about muscle length, and Golgi tendon organs, which provide information about muscle force.

• Standard muscle fibers are referred to as extrafusal fibers, and are the fibers that are responsible for generating force when they contract in response to the firing of motor neurons, such as alpha motor neurons.

• A sub-class of muscle fibers are referred to as intrafusal fibers, and these are the fibers that make up the muscle spindles, which get their name from their spindle shape. They are found in parallel with the extrafusal fibers, so that when the muscle stretches, they stretch as well.

• Specialized sensory fibers spiral around the intrafusal fibers, so that when the intrafusal fibers are stretched, the endings of the sensory nerves are stretched. These endings contain mechanosensitive ion channels, which respond to the stretch by conducting, inducing depolarization and action potentials.

• If a muscle shortens, the intrafusal fibers would ordinarily shorten as well, unloading the stretch receptors. However, some of the intrafusal fibers are innervated by a special motor neuron, the gamma motor neuron, which shortens the ends of the intrafusal fibers, stretching the central region of the intrafusal fiber so that the stretch receptors continue to be sensitive to changes in muscle length. Thus, it is possible for muscles to respond to dynamic changes in length, but also to provide information about their static lengths.

• This description is a simplification of the details of how muscle spindles work, but provides enough information to understand the basic principles of their operation.

• The Golgi tendon organs are located where a tendon meets a muscle. The fine endings of the sensory neuron interweave with the collagen fibers of the capsule containing the Golgi tendon organ, so that when the muscle is stretched, the nerve endings are compressed, and this induces stretch-sensitive ion channels in their membranes to depolarize and fire action potentials.

• Thus, Golgi tendon organs are very sensitive to the tension within a muscle, and average activity in the sensory neurons innervating these sensors is a good measure of muscle force.

The Stretch Reflex

• How do the proprioceptive sensors lead to appropriate behavioral responses?

• As you move your body, you repeatedly contact the environment: your foot strikes the ground, your hand picks up a glass, you sit down in a chair.

• Each of these actions, and many others, can cause muscles to stretch.

• Large, unexpected mechanical loads could, in principle, cause muscles to stretch so much that they start to tear away from their tendons, and this could lead to serious damage to the muscles and tendons. Indeed, this is a serious risk that may sideline an athlete.

• Maintaining posture as you sway from side to side also stretches muscles, and requires a feedback response to restore your body to a more stable position.

• The major way in which muscles restore their length is through the stretch reflex.

• If you have gone through a standard medical check up, the physician tested your reflexes in several ways.

• For example, shining a light in your eyes should have caused your pupils to contract, reducing the amount of light reaching the light-sensitive back of the eye, the retina.

• To test neuromuscular reflexes, the physician will often take a small hammer and sharply strike the patellar tendon, the tendon just below the knee.

• This stretches the tendon and the muscle that is attached to it, the quadriceps muscle.

• If your reflexes are normal, after a very short time, your leg kicks out towards the physician.

• The reason is that you've triggered a reflex that induces shortening of the quadriceps (to counteract the lengthening caused by the hammer tap), and relaxing the antagonist muscle (the hamstring muscle), which induces the lower part of your leg to kick outwards.

• Let's go through the steps of the reflex:
  • The hammer strikes the patellar tendon, and this lengthens the quadriceps muscle.
  • As a consequence, both the extrafusal and intrafusal muscle fibers are lengthened, and thus the sensory endings on the intrafusal fibers within the muscle spindles are activated.
  • The sensory neurons with the largest diameter within the muscle spindle are designated as the 1a sensory fibers, and they depolarize and generate action potentials.
  • The action potentials travel from the muscle via the dorsal root ganglion (where these sensory neurons have their cell bodies) and through the dorsal root (sensory input) into the dorsal horn of the spinal cord.
  • The dorsal horn, which is gray matter, because it contains cell bodies and synapses, is where the incoming signal from the sensory neuron travels across one synapse, and activates the fastest transmitting motor neuron, the alpha motor neuron, for the quadriceps muscle.
  • The synaptic input to the alpha motor neuron induces it to generate an action potential, and this action potential travels out through the ventral horn of the spinal cord and then through the ventral root (motor output) back to the quadriceps muscle, causing the extrafusal fibers to contract; this contraction counteracts the original stretch induced by the hammer tap.
  • As the muscle shortens, the intrafusal muscle fibers will shorten, and this will stop the activation of the 1a sensory fibers unless the motor neurons that induce stretch in the intrafusal fibers (the gamma motor neurons) have been activated; if both the alpha and gamma motoneurons are activated, then the muscle spindles can report both the initial lengthening and the actual (static) length of the muscle.
  • What about relaxing the antagonist muscle, the hamstring muscle?
  • When the action potential traveling along the 1a sensory fiber arrived in the dorsal horn of the spinal cord, the axon divided, and one branch synapsed on an inhibitory interneuron (a 1a inhibitory interneuron). This is in turn inhibits activity in the alpha motor neuron that would ordinarily activate the hamstring muscle. As a consequence, the hamstring muscle relaxes.
  • The result: the quadriceps contracts, the hamstring relaxes, and your leg kicks out towards the doctor, who is delighted to see that your reflexes are normal.

• When studied in isolation in anesthetized animals, reflexes are often very stereotyped.

• However, in an actual behavioral context, in freely behaving animals, reflexes can be powerfully modulated, and can even reverse under certain circumstances (for example, the responses of Golgi tendon organs may reverse sign when an animal is at rest or is walking, depending on what will be more appropriate for responses to sudden perturbations).

• Reflexes can also be a powerful window into disease. Since higher motor centers provide synaptic inputs to reflex pathways, lesions of descending motor pathways often lead to increased muscle tone and spasticity. Thus, an exaggerated reflex response (often referred to as hyperreflexia) may indicate damage to higher order interneurons.

Analyzing a Simple Reflex

You now have enough information to analyze a simple reflex pathway: the patellar reflex. In this simulation, we have connected a model of the quadriceps muscle to a model spindle fiber neuron (also referred to as the 1a afferent), which is sensitive to the muscle length. In turn, this spindle fiber neuron synapses on a model alpha motor neuron, which can activate the muscle, causing contraction of the quadriceps.

This simulation also includes an animation of the patellar reflex, which is greatly slowed compared to a real reflex so that you can see everything that is happening.

• The red ellipses are muscles:
  • The top muscle is the quadriceps, which is modeled in the simulation and whose shortening is controlled by the model.
  • The bottom muscle is the hamstring, which appears in the animation but is not modeled in the simulation.
  • When a muscle is stimulated to contract, it turns a dark red and shortens.
  • When a muscle is inhibited from contracting, it turns a pale red and lengthens due to the action of the antagonistic muscle.
• The black lines connecting the muscles to the lower leg are tendons.
• The trapezoidal white object is a hammer that strikes the patellar tendon, causing the quadriceps to stretch, initiating the reflex.
• The blue lines are neurons:
  • The large circles are neuron somas.
  • The V's represent the terminals of axons with excitatory connections.
  • One neuron has a small circle that represents the terminal of an axon with an inhibitory connection.
  • The zig-zag found on one neuron in the quadriceps is a spindle fiber stretch detector.
  • The neuron with the stretch detector is the spindle fiber neuron.
    • The spindle fiber neuron transmits action potentials through the dorsal root ganglion (where its soma is located) to the spinal cord, where it has excitatory connections with two neurons in response to stretching of the quadriceps muscle.
    • One of the spindle fiber neuron's targets is the alpha motor neuron, which stimulates the quadriceps to contract when excited, completing the reflex loop.
    • Both the spindle fiber neuron and the alpha motor neuron are modeled in the simulation.
    • The other target of the spindle fiber neuron is an interneuron contained in the spinal column. This is not modeled in the simulation, but is included in the animation for completeness.
    • The interneuron has an inhibitory connection to a motor neuron (also not modeled in the simulation) that normally causes the hamstring to contract. Inhibiting the contraction of this muscle is needed, since simultaneous flexing of the two muscles would not extend the leg.
  • When a neuron is excited, it will turn a dark blue.
  • When a neuron is inhibited, it will turn a pale blue.
  • Action potential propogation is schematically represented by traveling black dots.

Please open the simulation, preferably in a separate window:

Question 1. What happens if the muscle is stretched?

• A. First, see what the muscle does when it is not stretched. Set the Stretch parameter under Muscle Properties to 0 mm and run the simulation. How do the spindle fiber neuron, alpha motor neuron, and muscle behave? If you also run the animation, you will see that the hammer moves toward the patellar tendon, but it will not apply enough force to stretch the muscle.

• B. Now set the Stretch parameter to 5 mm. Changing this parameter represents a sudden stretch of the quadriceps muscle from its resting length of 90 cm to a stretched length of 90.5 cm (the period before the stretch is not plotted; hence this is the quadriceps muscle's "initial" length).
  • What do you observe happens to the length, to the force, and to the activity in the two neurons? Note that a negative force implies that the muscle is contracting. Explain your observations.
  • Please measure and record the following (you will need to zoom in to get these measurements):
    • The time at which the muscle reaches its minimum length (to the nearest millisecond),
    • The value of the minimum length (out to two decimal places), and
    • The time for the muscle to relax, measured as the time to return to within 0.1 cm of its rest length (i.e., to 89.9 cm) after the response (to the nearest millisecond).

• C. Repeat these measurements (using the same precision) when the muscle is stretched to 6 mm, 7 mm, 8 mm, 9 mm, and 10 mm. Please create the following three (separate) plots using the data you've collected in both this part of the question and part B:
  • Along the x axis of each plot, plot the stretch length (5, 6, 7, 8, 9 and 10 mm).
  • Along the y axis, plot
    • (1) the time at which the muscle reached its minimum length,
    • (2) the value of the minimum length, and
    • (3) the time for the muscle to relax.
  • Explain what your plots show.

• D. How does the muscle respond to stretch if the reflex is disabled? Reset the simulation, and set the Reflex threshold length (under the Spindle Fiber Neuron Properties) to 92 cm, which prevents the reflex from being activated in the range of stretch lengths you are exploring.
  • Describe how the neurons and muscle now respond to stretch.
  • Why would the reflex be useful for preventing tissue damage if a strong force is suddenly applied to the muscle?

Question 2. What are the characteristics of the spindle fiber neuron and its synapse onto the alpha motor neuron?

• A. Reset the simulation. Stretch the muscle by 0.85 mm.
  • What do you observe in the spindle fiber neuron and in the alpha motor neuron?
  • What kind of synaptic potential does the spindle fiber neuron induce in the alpha motor neuron? Explain.

• B. Disconnect the spindle fiber neuron and the alpha motor neuron by setting the synapse conductance to 0 (from 0.05 microSiemens) under the heading Spindle to Alpha Synapse Properties.
  • What changes? Does the muscle shortening change? Explain.

• C. Now stretch the muscle by 5 mm while the synapse conductance is still 0.
  • What do you observe in the spindle fiber neuron, in the alpha motor neuron, and in the muscle?
  • For approximately how long does the spindle fiber fire action potentials? What do you think determines this?

• D. Restore the connection between the spindle fiber neuron and the alpha motor neuron by setting the synapse conductance to 0.05, and again stretch the muscle by 5 mm.
  • What do you observe? After making this change, how long does the spindle fiber fire action potentials? Why does changing this synaptic conductance have this effect on the presynaptic cell? Outline how the entire reflex is likely to work.

Question 3. What are the characteristics of the alpha motor neuron and its synapse onto the muscle, called the the neuromuscular junction (NMJ)?

• A. Reset the simulation. Note once more that the stretch is set to 5 mm. Under Neuromuscular Junction Properties, set the synapse strength to 0 (from its original value of 0.01), effectively disconnecting the alpha motor neuron and the muscle.
  • What do you observe in the spindle fiber neuron, in the alpha motor neuron, and in the muscle?
  • For approximately how long does the alpha motor neuron fire action potentials? What do you think determines this?

• B. Restore the connection between the alpha motor neuron and the muscle by setting the NMJ synapse strength to 0.01, and again stretch the muscle by 5 mm.
  • What do you observe? After making this change, how long does the spindle fiber fire action potentials? Why does changing this synaptic strength have this effect on the presynaptic cell? Use your answer to 2D and your observations in part 3A to explain how the entire reflex works.

Question 4. What happens if the muscle continues to report changes in length even after it has shortened?

• The simulation does not have a representation of the gamma motor neurons that allow the muscle to continue to report its length even as it shortens and unloads the spindle fibers. As a crude substitute for this, however, we can increase the time constant of the synapse between the spindle fiber and the alpha motor neuron.

• Reset the simulation. Under Spindle to Alpha Synapse Properties, double the values of the Synapse rise time constant (from 10 ms to 20 ms), and the Synapse fall time constant (from 25 ms to 50 ms). The stretch length should be 5 mm.
  • Compare the following when the larger time constants are used to when the default time constants are used:
    • (1) the intensity of firing in the alpha motor neuron (a qualitative answer will suffice),
    • (2) the minimum length of the muscle during the contraction (out to two decimal places), and
    • (3) the maximum muscle force (to the nearest millinewton).
  • What do you observe? Explain. What is the advantage of providing information about the length of the muscle even after it has shortened? Consider, for example, what would happen if you were holding a heavy load and managed to shorten the muscle to a length at which the spindle fibers were no longer activated in the absence of gamma motor neuron activity. What would the muscle do? How does the gamma motor neuron activity help the system maintain the muscle at a shorter length?