SP

Reflexes, rhythmical motor behaviors, and voluntary actions.

Reflexes

  • Reflexes are the simplest forms of motor behavior, characterized by:
    • Automatic and fast responses to external stimuli.
    • Stereotyped movements initiated by low-level circuits in the spinal cord or brainstem.
    • Examples include sneezing, pupil constriction, and tendon tap responses.
    • Not easily willed into action.
    • Can be modulated or suppressed by input from other CNS regions.

Types of Movement

  • Reflexes:
    • Simplest, stereotyped, automatic, and fast responses.
    • Controlled by low-level circuitry in the spinal cord or brainstem.
    • Triggered by specific external stimuli.
    • Cannot be willed into action but can be modulated.
  • Rhythmical Behaviors:
    • Repetitive, cyclical movements like walking, chewing, and breathing.
    • Involve central pattern generators in the lower CNS.
    • Activated and modulated by higher CNS centers.
  • Voluntary Movements:
    • Most complex, consciously activated movements.
    • Involve the highest level of the CNS (cerebral cortex).
    • Can improve with practice and learning.

Other Motor Behaviors

  • Innate Behaviors:
    • Species-specific behaviors, such as courtship displays, social vocalizations, defensive responses, maternal behaviors, and emotional expressions.
    • Controlled by regions in the periaqueductal gray matter of the brainstem.
  • Posture and Balance:
    • Have both reflexive and voluntary components.

Coordination of Multiple Muscles

  • All movements require coordination of multiple muscles, involving:
    • Excitation of some muscles.
    • Inhibition of others.
    • Example: Leg extensor muscles must be silenced during the swing phase of gait to allow leg flexor muscles to lift the leg.
    • Motor coordination involves linking contractions and relaxations of several muscles.

Involvement of Somatosensory Receptors in Reflexes

  • Somatosensory receptors (muscle spindles, Golgi tendon organs, tactile receptors, nociceptors, etc.) trigger different reflexes.
  • Tactile and proprioceptive afferents ascend to the dorsal column nuclei in the brainstem and then project to the thalamus and somatosensory cortex.
  • Sensory afferents also send collaterals into the spinal cord gray matter to instigate reflexes.

Study of Reflexes

  • Charles Sherrington studied reflexes to understand general principles about neural circuits.
  • Challenges in studying reflexes:
    • Anesthetics depress the nervous system's excitability, suppressing the behaviors one wants to study.

Experimental Preparations

  • Decerebrate Preparation:
    • Cerebrum is removed under anesthesia, leaving the brainstem intact.
    • Eliminates conscious awareness, allowing discontinuation of anesthesia.
    • Vital functions carried out by the brainstem remain intact.
  • Spinalization:
    • Spinal cord is transected, and experiments are conducted below the lesion.
    • Both preparations (decerebrate and spinalized) lead to robust and stable responses due to the elimination of descending influences.

Stretch Reflex

  • Also called the myotatic reflex or tendon tap reflex.
  • Triggered by an external perturbation that abruptly lengthens a muscle.
  • Example: A knock to the forearm extends the elbow and lengthens the biceps muscle (agonist).
    • Lengthening activates Ia afferents from muscle spindles in the agonist muscle.
    • Ia afferent activity excites motor neurons in the spinal cord that innervate the same muscle.
    • The stretched muscle contracts, restoring the limb to its original configuration.
    • Ia afferents also excite inhibitory interneurons that suppress antagonist (triceps) muscles.
  • Reciprocal Inhibition:
    • Reflex suppression of antagonistic muscles when agonist muscles are induced to contract.
  • Involves coordination across multiple muscles (excitation of agonist and inhibition of antagonist).

Role of Stretch Reflex

  • Rapid response to external perturbations that displace body parts.
  • Maintenance of upright posture.
    • Small sway forward lengthens muscles in the back of the leg, triggering a stretch reflex to contract those muscles and pull the body back.
    • A backward sway lengthens muscles in the front of the leg, triggering a stretch reflex to pull the body forward.

Clinical Evaluation of Stretch Reflex

  • Physicians evaluate the stretch reflex using a tendon tap with a hammer.
    • The tendon tap elicits an intense burst of activity on Ia afferents, triggering the stretch reflex.
  • Diagnostic Value:
    • Weak or absent response: Indicates dysfunction in peripheral nerves (neuropathies) due to conditions like diabetes, kidney dysfunction, vitamin deficiencies, or alcoholism.
    • Exaggerated response: Indicates damage to brain centers or corticospinal pathways that normally modulate reflexes.

Flexor Reflex

  • Triggered by activity on Ad afferents from nociceptors.
  • Ad axons underlie first pain.
  • Example: Stepping on a tack.
    • Ad activity is communicated to neurons in the dorsal horn of the spinal cord.
    • One set of dorsal horn neurons gives rise to the spinothalamic pathway (conscious perception of pain).
    • Another set activates excitatory interneurons that excite motor neurons supplying flexor muscles in the limb.
    • Coactivity of limb flexor muscles pulls the limb away from the offending stimulus.
    • Another branch of Ad axons activates interneurons, leading to reciprocal inhibition of extensor muscles on the same side of the spinal cord.

Crossed Extensor Reflex

  • Coupled with the flexor reflex.
  • Nociceptive Ad activity on one side of the body triggers responses in the opposite limb.
    • Signals trigger a flexor reflex and engage the crossed-extensor reflex through interneurons that cross over to the opposite side of the spinal cord.
    • Interneurons excite motor neurons supplying extensor muscles in the unaffected limb and inhibit motor neurons innervating flexor muscles.
    • Leads to rapid limb extension, pushing the limb downward for support and propelling the body away from the painful stimulus.

Other Reflexes

  • Inverse Myotatic Reflex:
    • Triggered by muscle force leading to excitation of Ib afferents from Golgi tendon organs.
    • Through spinal cord interneurons, Ib input is transformed into inhibition of the contracting muscle (agonist) and excitation of the antagonist muscle.
    • May have little practical use and is revealed when normal descending influences are artificially removed.
  • Babinski Reflex:
    • Elicited in healthy infants by stroking the skin on the sole of the foot, causing hyperextension of the large toe and splaying of other toes.
    • Disappears with CNS development but emerges in adults with damage to corticospinal pathways.

Sherrington's View on Reflexes

  • Simple reflex is an abstract conception because all parts of the nervous system are interconnected.

Primary Role of Somatosensory Receptors

  • Sherrington was awarded the Nobel Prize in Physiology (1932) for his work on reflexes, particularly the role of inhibition in the CNS.
  • Experiments identified the neural elements involved in the production of reflexes.

Voluntary Movements

  • Sherrington demonstrated the importance of somatosensory signals in voluntary motor behaviors through experiments involving dorsal root sections in monkeys.
  • Removal of somatosensory input abolished movements of the hand and foot, including grasping.
  • Monkeys would not use the deafferented limb even when hungry or when food was placed in their hand.
  • Electrical stimulation of the motor cortex evoked movements as readily in deafferented limbs as in intact limbs.
  • Somatosensory signals play an essential role in formulating and shaping commands for voluntary movements.
  • Complex voluntary movements can be performed without vision, but even simple movements cannot be produced without somatosensation.
  • The importance of somatosensory afferents is often undervalued by solely emphasizing their role in reflexes or feedback corrections.

Reflex Interference with Voluntary or Rhythmical Movements

  • Every movement activates somatosensory afferents, which could trigger reflexes that interfere with the intended action.
  • Mechanisms are available to override reflexes that would interfere with voluntary or rhythmical behaviors.
    Example:
    * When rapidly extending the elbow to catch a ball, descending commands activate triceps motor neurons, causing elbow extension and biceps lengthening.
    * Biceps lengthening provokes activity on biceps muscle spindle Ia afferents. If nothing else were to happen that the excitation of the biceps motor neurons would cause the biceps to contract preventing the catching motion

Convergence onto Common Interneurons

  • Interneurons in reflex pathways are not the private property of a reflex pathway but receive converging synaptic input from many sources.
  • A reflex is instigated only if the collective synaptic input is sufficient to activate the interneurons.
  • Anders Lundberg and Elzbieta Jankowska demonstrated this concept.

Experiments on Convergence

  • Changes in membrane potential of motor neurons were recorded in response to stimulation of peripheral afferents, descending pathways, and near-simultaneous stimulation of both.
  • Stimulation of either site alone did not elicit a response, but simultaneous activation caused a robust depolarization.
  • Sensory afferent and descending pathways converge upon common excitatory interneurons.
  • Activation of either pathway alone is insufficient to excite the interneurons, but simultaneous activation brings the interneurons to threshold.

Common Inhibitory Interneurons Example

  • When stimulating the same sensory nerve or cortex no response was evoked.
  • However, when the to pathways were activated at nearly the same time, hyperpolarization was recorded in the motor neuron converging onto common inhibitory interneurons.

Integration of Sensory and Descending Inputs

  • Jankowska & Lundberg (1981) discovered that virtually all spinal interneurons receive converging inputs from wide arrays of sensory and descending inputs.
  • Ia inhibitory interneurons:
    • Receive excitatory inputs from Ia afferents of muscle spindles and sensory afferents from skin and joints.
    • Receive inhibitory input from Ia inhibitory interneurons of the antagonistic muscle.
    • Receive descending projections from the spinal cord, cortex, and brainstem centers (red and vestibular nuclei).
  • Ib inhibitory interneurons:
    • Receive input from Golgi tendon organ Ib afferents, Ia afferents from muscle spindles, and sensory afferents from skin and joints.
    • Receive descending inputs from the cortex, red nucleus, and reticular formation.
    • Activation of interneurons depends on cooperation across sets of inputs, where single type of sensory afferent activity may be insufficient to trigger a reflex.

Presynaptic Inhibition

  • Inhibitory synaptic inputs synapse onto the presynaptic terminals of sensory afferents.
  • Frank and Fuortes (1957) identified presynaptic inhibition.

Experiment

  • Recorded changes in membrane potential in motor neurons supplying a lower leg muscle.
    • Stimulation of Ia afferents caused expected depolarization.
    • Stimulation of a nerve emerging from an upper leg muscle had no effect.
    • Simultaneous stimulation of both sites greatly suppressed the direct excitation from the Ia afferents.

Mechanism

  • Stimulation of site 2 caused inhibition of the presynaptic terminals of the Ia afferents, mediated by a previously unidentified class of inhibitory interneurons.
  • Later work by John Eccles and colleagues validated this idea.

Characteristics

  • Virtually all somatosensory afferents are subject to presynaptic inhibition.
  • Found in the spinal cord, brainstem, cerebellum, hippocampus, amygdala, and retina.
  • Interneurons mediating presynaptic inhibition are GABAergic, driving the membrane potential of sensory afferent presynaptic terminals toward the equilibrium potential of Cl−.
  • Action potentials entering the presynaptic terminal are attenuated, reducing activation of voltage-gated Ca^{2+} channels and neurotransmitter release.

Sources of Input to Interneurons Mediating Presynaptic Inhibition

  • Early work showed that virtually all somatosensory afferents can induce presynaptic inhibition in other sensory afferents.
  • Substantial presynaptic inhibition of somatosensory afferents is caused by stimulation of somatosensory and motor cortices, and the brainstem.
  • More recently, direct projections from somatosensory and motor cortices to interneurons that mediate presynaptic inhibition in the spinal cord of sensory afferents were demonstrated (Moreno-Lopez et al. 2021).
  • These descending inputs are distinct from those that produce movements.
  • Robust presynaptic inhibition arises from central pattern-generating circuits to mitigate interference of reflexes during rhythmical motor behaviors.
  • During voluntary movements, presynaptic inhibition greatly attenuates responses in spinal neurons receiving sensory input, minimizing interference of voluntary behaviors by reflexes (Seki et al. 2003).

Voluntary Movements Unimpeded by Reflexes

  • Descending commands from the cortex excite triceps motor neurons, causing triceps contraction and elbow extension, which stretches the biceps.
  • To prevent the stretch reflex from impeding the movement:
    • Inhibitory interneurons (Ia IN) could be enlisted to directly inhibit the motor neurons supplying the biceps muscle.
      • Descending pathways converge onto and excite those common interneurons in parallel with those exciting triceps motor neurons.
    • Descending inputs (path B, Figure 10) may activate interneurons mediating presynaptic inhibition (pre IN, Figure 10).
      • Presynaptic inhibition limits the transmission of Ia activity onto the biceps motor neurons.

Modulation of Reflexes

  • Crucial sensory signals associated with voluntary movement are still conveyed to the brain.
  • Genetic deletion of inhibitory interneurons that cause presynaptic inhibition leads to oscillations of the forelimb during reaching (Fink et al. 2014).
  • Genetic deletion of interneurons mediating presynaptic inhibition driven by central pattern generators causes excessive motion of hindlimbs during locomotion (Koch et al. 2017).

Spasticity

  • Damage to descending motor pathways can lead to uncontrolled muscle contractions (spasticity).
  • Damage to descending pathways that suppress reflexes may be partially responsible for spasticity.
  • Stretch reflexes below the level of the lesion may become stronger and longer-lasting.
  • Spastic contractions can lead to joint and bone deformities, impede basic activities, and cause pain.

Clinical Approaches to Treating Spasticity

  • Dorsal rhizotomy: Cutting the dorsal roots to eliminate sensory afferent input triggering reflexes.
  • Continuous infusion of a GABA agonist: Dampens the excitability of spinal reflex circuits, reducing spasticity.

Summary

  • Reflexes are the simplest type of motor behavior, triggered by external stimuli detected by peripheral sensory receptors.
  • Willed movements excite many of the same somatosensory receptors and sensory afferents that cause reflexes.
  • Two systems prevent reflexes from occurring during self-produced movements:
    • Interneurons receive input from reflex-designated sensory afferents and descending, interneuronal, and peripheral sources, serving as decision hubs.
    • Presynaptic inhibition suppresses sensory signals by inhibitory interneurons acting at the terminal branches of primary afferents, preserving sensory information delivery to higher centers.
    • Suppression is driven by inputs descending in parallel with commands to produce voluntary or rhythmical movements.