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Muscle Makes Behavior Possible

The nervous and muscular systems are entirely unique to animals.
Their functions are so intertwinted, that they are sometimes collectively called the neuromuscular system.

Muscle tissue is composed of specialized contractile cells/fibers
that may be either

  • smooth (involuntary control)
    • provides musculature of hollow and tubular organs
  • striated
    • cardiac (involuntary control)
    • skeletal (voluntary control)

Vertebrate Skeletal Muscle Anatomy

Vertebrate skeletal muscle is composed of long, multinucleate
muscle cells (=muscle fibers).
Each muscle fiber consists of hundreds of parallel myofibrils.
Each myofibril is a long strand of proteins comprising
end-to-end contractile subunits called sarcomeres.

Connective tissue sheaths multiple muscle fibers into a fasciculum.
There are 10-100 muscle fibers/fasciculum, depending on which muscle.

Connective tissue bundles multiple fasciculi together into a muscle.

Nerves and blood vessels are embedded within the muscle.

At either end of the muscle, the connective tissue sheaths form tendons.
These connect the muscle to attachment points on the skeleton.

Vertebrate Muscle Cell Anatomy

  • The sarcolemma is the cell membrane of a muscle cell.

  • Sarcoplasmic reticulum is a specialized endoplasmic reticulum that regulates cytoplasmic [Ca+].

  • t (transverse) tubules are deep invaginations of the sarcolemma that allow membrane depolarization to quickly enter the cell's interior.

  • Terminal cisternae are enlarged regions of sarcoplasmic reticulum on either side of the t tubules. They store Ca+.

  • Sarcomere Structure

    A myofibril consists of hundreds of sarcomeres, end to end.
    Upon staining, the sarcomeres appear striated.
    Striation is due to alternating bands of thin actin (light) and thick myosin (dark).

    Each sarcomere has anatomical landmarks:

    • A band - length of a myosin filament, including actin overlap
    • H band - myosin filaments only
    • I band - actin filaments only
    • M line - region of myosin interlacing/anchoring
    • Z line/disc - region of actin anchoring
    The sarcomere is the contractile subunit of striated muscle.

    The Cross Bridge Cycle in skeletal muscle.
    (Required Video!)

    Muscle Contraction: The Cross Bridge Cycle

    Both skeletal and smooth muscle contract
    via similar interactions between two proteins:
    • actin - long, thin filaments
    • myosin - short, thick filaments

    The cycle is generally divided into four steps.

      1. Cross Bridge Formation
      2. Power Stroke
      3. Cross Bridge detachment
      4. Re-activation of Myosin Head

    Twitches and Tetanus

    The point of contact between spinal motor neuron and muscle cell is the neuromuscular junction.
    • AP frequency at the neuromuscular junction determines muscle tension.
    • A muscle twitch is one contraction and relaxation of a skeletal muscle fiber.
    • When a muscle is stimulated repeatedly, successive twitches sum.
    • The overall response to repeated simuli is greater than a single stimulus response.
    • This additive effect is known as summation.

    Amplitude of summed contractions depends on time interval between stimuli.

    • Low frequency stimulation results in summation
    • Higher frequency stimulation results in a constant (fused) contraction, tetanus.
    • A tetanic contraction is sustained muscle contraction evoked when the motor nerve innervating a muscle fiber emits APs at a very high rate.
    • Tetanus--not to be confused with the disease--is the maximum contractile response the muscle can achieve.

    A Public Service Message: Be Up to Date on your Tetanus Vaccination!

    Too Much Tetanus

    Tetanus toxin is produced by the anaerobic bacterium Clostridium tetani.
    • The LD50 (mice) of tetanus toxin is approximately 2.5 - 3.0 ng/kg
    • Of all known toxins, only botulinum (LD50 2.0 ng/kg) has higher potency.

    If a Clostridium tetani spore enters a wound, it produces toxin that binds to peripheral nerves.

    Toxin is transported transcytotically to CNS inhibitory neurons.

    Modified toxin cleaves synaptobrevin, a critical component of the SNARE complex.

    Remember the SNARE complex? Quiz Question!

    Affected motor neurons to become hyperexcitable.
    At full progression of infection, essentially all motor neurons generate APs.
    The resulting constant tetanic contractions of the skeletal muscles are almost invariably fatal.

    Smooth Muscle

    • is composed of layers of interdigitating, spindle-shaped cells
    • composed of three types of filaments
      • thick myosin filaments
      • thin actin filaments
      • intermediate cytoskeletal filaments
    • lacks striations: no myofibrils or sarcomeres
    • myosin and actin form "cross bridges" that change cell shape upon contraction
    • located in the walls of hollow organs
      • intestine
      • blood vessels
      • reproductive organs

    Smooth Muscle Innervation

    Varicosities (swellings) along the autonomic neuron axons
    innervating smooth muscle contain neurotransmitter vesicles.
    Neurotransmitter is released when an AP passes the varicosity.

    Varicosities from one axon may contact several muscle cells.
    A single muscle cell may be innervated by both sympathetic and parasympathetic neurons.

    • Multiple muscle cells can be influenced by a single neuron.
    • Single muscle cells can be influenced by multiple neurons.

    Preganglionic neurons release acetylcholine.
    Postganglionic neurons release epinephrine and norepinephrine.

    The same neurotransmitter may produce opposite effects by binding to different receptors. For example, noepinephrine

    • enhances vascular muscle contraction when bound to α adrenergic receptors (excitatory)
    • relaxes bronchiole smooth muscle when bound to β-2 adrenergic receptors (inhibitory)

    The nature of the response in smooth muscle thus depends on the combination of

    • neurotransmitter identity
    • type of receptor
    • second messenger molecules

    Smooth Muscle Contraction

      Actin filaments are anchored to dense bodies composed of
      • α-actinin
      • vimentin
      • desmin

      Smooth muscle Cross Bridge Activation


      • Calcium activates calmodulin, a regulatory protein.
      • Calmodulin activates myosin light-chain kinase (MLCK).
      • Upon activation, MLCK phosphorylates myosin.
      • Phosphorylated myosin binds to actin.
      • Cross Bridge Cycle commences.
      • (In smooth muscle, troponin is replaced by tropomyosin.)


      • Myosin is dephosphorylated by myosin light-chain phosphatase (MLCP).
      • Dephosphorylated myosin has no affinity for actin.
      • Dissociation of myosin from actin causes smooth muscle to relax.

    Smooth Muscle: Multi-unit or Single-unit

    In multi-unit smooth muscle
    • each cell behaves/contracts independently
    • relatively few gap junctions between cells
    • more varicosities per cell
    • most common in muscle that must be constantly contracted, such as sphincter

    In single-unit smooth muscle

    • cells contract in a coordinated fashion.
    • numerous gap junctions between cells create an electrically continuous syncytium.
    • fewer varicosities per cell
    • most common in rhythmically active smooth muscle, such as uterus and digestive tract, where coordinated contraction is necessary

    Smooth Muscle: Tonic vs. Phasic Contractions

    Tonic smooth muscle
    • contracts relatively slowly
    • are almost constantly contracted
    • typically occur in multi-unit smooth muscle
      • digestive tract sphincters
      • vascular smooth muscle
      • urinary bladder sphincter

    Phasic/rhythmic smooth muscle

    • contracts relatively rapidly
    • contracts only periodically, when necessary
    • typically occur in single-unit smooth muscle
      • digestive tract
      • certain regions of the urogenital tract such as
        • bladder wall (for release of urine)
        • epididymis wall (for expulsion of sperm)
        • uterine myometrium (for parturition contractions)

    Neural Control of Skeletal Muscle: The Basis of Animal Behavior

    A major function of an animal's nervous system is to generate its behavior, from simple reflexes to complex mating behaviors.

    The brain is central to the
    • initiation
    • coordination
    • regulation
    ... of normal muscle movement.

    Together, the
    • cerebral cortex
    • cerebellum
    • basal ganglia
    ... act via connected circuits to coordinate and control muscle and movement.

    By OpenStax College - Anatomy & Physiology, Connexions Web site

    The Cerebral Cortex

    As you have seen, sensory processes are maintained
    in somatotopic maps in the brain.

    Somatotopy is the point-for-point correspondence
    between a body part and an area of the cerebral cortex that controls it.

    A specialized region of the cortex receives afferent (sensory) information from its somatic "partner", and responds with efferent (motor) commands.

    Neurons that send motor commands to muscle cells comprising
    the body of a muscle are known as alpha (α) motor neurons.
    The muscle cells themselves are sometimes called alpha (α) muscle cells.

    The Cerebellum

    The vertebrate cerebellum is a large, highly convoluted hindbrain structure.
    • consists of an outer cerebellar cortex
    • which feeds output to the underlying deep cerebellar nuclei

    The cerebellum does not initiate muscle action. It is involved in

    • coordination
    • precision
    • accurate timing
    ...of muscle action.

    The cerebellum receives brain and spinal neuron sensory input.
    Its function is to fine-tune muscle/motor activity.

    An animal with a cerebellar lesion can still perform clumsy, disordered voluntary movements that may be accompanied by tremors.

    Basal Ganglia

    The basal ganglia are groups of nuclei in the forebrain and midbrain.

    These receive excitatory input from many parts of the cerebral cortex.

    They are involved in

    • selecting movements
    • initiating selected movement
    • suppressing competing or unwanted movements

    Neural Circuits and Control of Muscles

    Neural circuits can govern motion processes either globally (most movements) or locally(reflexes).

    Global control is accomplished via circuits that connect sensory (afferent) receptors (and neurons) and motor (efferent) neurons to the brain via the spinal cord.

    Local control is accomplished via circuits that connect sensory (afferent) receptors (and neurons) and motor (efferent) neurons to the spinal cord, but do not involve the brain.

    Nervous System Circuits

      A neural circuit is analogous to an electrical circuit:
      a closed loop network providing a return path for current.

      A motor circuit can elicit a coordinated response in an animal's muscles.

      • Sensory receptor cells transform environmental stimuli into electrical signals.
      • CNS interneurons integrate incoming signals from sensory receptors.
      • CNS generates an integrated pattern of electrical impulses.
      • CNS sends these outgoing motor commands to PNS --> muscles in response to sensory stimuli.

    By debivort - Own work

    Spinal Cord Circuits

    The vertebrate spinal cord has two types of circuits:
    • local circuits
      • reside within a single spinal cord segment
      • e.g., simple spinal reflex circuit
      • relatively primitive
    • ascending/descending
      • ascending (sensory) circuits send information from spinal cord to brain
      • descending (motor) circuits send information from brain to spinal cord

    Muscle Spindles

      Muscle spindles are sensory receptors within the belly of a muscle.

      A muscle spindle fiber

      • detects changes in muscle length
      • is embedded in extrafusal (garden variety) muscle fibers
        (from the Latin fusus meaning "spindle")
      • has both sensory and motor components

      Muscle spindles play a role in

      • proprioception via
      • regulating muscle contraction
      • resisting muscle stretch

    Muscle Spindle Components and Organization

    Each spindle is encapsulated in connective tissue.
    Spindles are aligned parallel to extrafusal muscle fibers.

    The system consists of

    • extrafusal muscle fibers (alpha, α) - bulk of the muscle
    • intrafusal muscle fibers (gamma, γ) - fibers inside the spindle

    • alpha (α) motor neurons
      • the most common type of muscle motor neuron
      • synapse onto extrafusal (α) muscle fibers
      • transmit APs from CNS to extrafusal muscle fibers
      • (we will use "motor neuron" (no Greek letter) synonymously)

    • afferent sensory neurons (1a are the largest type)
      • sensory terminals coil around noncontractile intrafusal (γ) muscle fibers
      • carry stretch sensory information from the spindle to the CNS
      • in the diagram, these are are shown in blue

    • gamma (γ) motor neurons
      • synapse on either side of the noncontractile center
      • send APs from the CNS to regulate muscle spindle fiber contraction
      • in the diagram, these are shown in red

    Muscle spindles are too few and too small to sense muscle tension themselves.
    Instead, they sense and send information about
    • muscle length
    • rate of change of muscle length the CNS.

    The Principle of Reciprocity

    Muscles (and groups of muscles) are usually arranged in antagonist pairs. One muscle group's action opposes that of the other
    • flexor muscles bend the body part
    • extensor muscles straighten the body part

    • agonist muscles work together with each other.
    • antagonist muscles work in opposition to each other.

    A motor command for a particular movement must coordinate

    • contraction of agonists (excitatory signals)
    • relaxation of antagonists (inhibitory signals)

    1a afferent neurons synapse onto sets of motor neurons that send

  • excitatory signals to a particular muscle
  • inhibitory signals to that muscle's antagonist

    Such reciprocal muscle control ensures that muscle groups
    do not counteract each other and suppress movement.

  • Involuntary Movement of Skeletal Muscle: Reflexes

    A reflex is a local action performed without brain involvement. Two well studied reflexes are the

    The Stretch Reflex

    The simplest reflex involves only
    • 1a afferent/sensory neurons
    • α motor neuron
    ...which synapse directly onto each other in the spinal cord.

    The reflex:

      1. Intrafusal muscle fibers are stretched.
      2. AP is generated in 1a sensory neurons.
      3. 1a sensory neurons APs travel to the spinal cord.
      4. If threshold is reached, an AP is generated in the α motor neuron.
      5. Motor neuron APs travel directly back to the muscle.
      6. Muscle flexes without brain involvement.

    Quiz Question!

    Other Functions of the Stretch Reflex

    The stretch reflex also contributes to load compensation.

    If a large animal jumped onto your back, the added weight would buckle your knees.
    The stretch reflex helps prevent this.

    • Stretched extensor muscles activate muscle spindles.
    • Muscle spindles excite extensor muscle motor neurons.
    • Extensor muscles contract, generating force to counteract increased load.
    Stretch receptors maintain body posture by counteracting
    • small changes in load
    • muscle fatigue
    • anything that unbalances muscle group agonists vs. antagonists

    Flexion and Crossed Extensor Reflexes

      If you step on a sharp tack, your thigh flexors will
      reflexively pull your foot away from the noxious stimulus.
      This is the flexion reflex

      Flexion-reflex sensory neurons terminate in skin, muscles and joints.
      They respond to painful/noxious stimuli.

      Unlike stretch reflex neurons, flexion-reflex sensory neurons
      communicate with muscle motor neurons via CNS interneurons.

      1. Flexion-reflex sensory neurons stimulate CNS interneurons.
      2. Stimulated CNS interneurons excite

      • flexor muscle motor neurons
      • extensor muscle-inhibiting interneurons

    As your foot pulls away from the tack, your body must
    compensate by flexing the other leg.
    This is the crossed extensor reflex

    The nociceptor in your foot branches to connect with four spinal cord interneurons.

    In the leg that stepped on the tack:

    • nociceptor --> excitatory interneurons --> excite flexor α motor neurons
    • nociceptor --> excitatory interneurons --> inhibitory interneurons -->
      inhibit extensor α motor neurons
    • leg flexes upward, avoiding the noxious stimulus

    In the opposite leg:

    • nociceptor --> excitatory interneurons --> inhibitory interneurons -->
      inhibit flexor α motor neurons
    • nociceptor --> excitatory interneurons --> excite extensor α motor neurons
    • leg extends, stabilizing the body

    (Change speed to 0.5 for a clear view; use "settings" icon.)

    Other Functions of the Cross-Extension Reflex

    The crossed extensor reflex is also involved in the generation of repetitive motion
    • walking
    • arm swinging while walking
    • wing flapping
    • etc.

    Some mammals have an inborn, anomalous cross-extension pattern:
    they naturally describe a gait known as pacing.

    Pacing mammals move both limbs on the same side together,
    rather than in opposition.

  • Normal "trotting" gait: top video.
  • Anomalous "pacing" gait: bottom video (00:10)

    Pacing is a faster gait than trotting, and tends to be inherited in a dominant fashion.

    In a few species, pacing is the normal gait.
    This is true of bears, cats, camels, elephants, and giraffes.

  • Reflex Pathways and Voluntary Movement

    The vast majority of motor neurons are controlled by the CNS, not reflex arcs.

    Reflex pathways help modulate voluntary movement.

    Load Compensation: Stretch Reflex + Voluntary Movement

    Suppose someone decides to pick up an object, such as a voting ballot.
    This is a voluntary movement.

    The CNS must perform a complex analysis to

    • estimate the muscle power needed
    • command motor neuron activation
    ... to correctly perform the action

    The stretch reflex mediates load compensation,
    augmenting muscle contraction in case of unexpected extra weight/resistance.

    A CNS command for a voluntary movement excites both α and γ motor neurons.
    This process is known as α-γ coactivation.

    Coactivation has two functions

    • maintains ongoing sensitivity of muscle spindle during muscle shortening
      • (A contraction (1) slackens the intrafusal muscle fiber, (2) unloads the muscle spindle,
        and thus (3) decreases sensitivity.)
    • allows muscle spindle to determine if muscle shortens, as expected

    If the ballot is light, and the CNS has correctly estimated its weight...

      Coactivation of α and γ motor neurons triggers contraction of both
      • muscle spindle intrafusal fibers (γ motor neurons)
      • muscle extrafusal fibers (α motor neurons)
      • Both intrafusal and extrafusal fibers are shortening together.
      • 1a afferent neuron generates no APs.
      • Message to the CNS: "Muscle is contracting, not stretching. All is good."

    If the ballot is heavier than it looks, and the CNS has underestimated its weight...
    • γ motor neurons trigger contraction of intrafusal fibers.
    • BUT α motor neurons DO NOT provide sufficient APs for extrafusal fiber contraction.
    • Result: shortening of intrafusal fibers WITHOUT shortening of extrafusal fibers
    • Message to the CNS: "Error! Muscle failed to shorten! Adjust!"
    • The stretch receptor activates:
      • The 1a afferent neuron sends APs to the α motor neuron
      • α motor neuron increases AP rate.
      • More muscle tension is provided to overcome the load.


      I. Picking up the ballot is under voluntary, CNS control.
      II. Load compensation is mediated by the involuntary stretch reflex.

    Neural Generation of Rhythmic Behavior

    Most animal behavior consists of action patterns.
    An action pattern is a sequence of effector actions resulting from sequences of nervous system motor output.

    These sequences can be complex, variable, and difficult to study.
    A rhythmic behavior is a stereotyped, repetitive sequence of movements.

    Because the motor output is stable, repeatable, and predictable from cycle to cycle of the activity,
    rhythmic behaviors are a well-studied model of the basis of more complex behaviors.

    Rhythmic Behavior in Insects: Flying

    Simple up and down wing oscillation is generated by a set of levator and depressor muscles.
    • depressors are activated when wings are up
    • levators are activated when wings are down

    Alternating bursts of action potentials in levator and depressor neurons generate wingbeats.

    Flight is sustained by a central pattern generator (CPG):

    • A CPG is a neural circuit in the CNS (nerve cord).
    • CPG generates patterned activation of motor neurons to antagonistic muscles.
    • CPG governs repetitive behavior pattern without sensory feedback.
    • The rhythmic pattern is under CNS (nerve cord) control.

    In 1961 Donald Wilson demonstrated that repetitive flight motion is generated primarily by a CPG in locusts.

    • He cut wing hinge nerves to remove sensory input from the wings.
    • Treated locusts could maintain flight without any sensory feedback.
    • This demonstrated that flight is under central (ventral nerve cord), not peripheral, control.

    • HOWEVER, wingbeat frequency in treated locusts was slower than normal.
    • Later experiments: sensory input provides general excitation to the CNS.
    • Sensory feedback may affect the quality of rhythmic behavior.

    Rhythmic Behavior in Vertebrates: Walking

    Many of the principles operating in insects also apply to vertebrates.
    One can consider the vertebrate nervous system to consist of three parts that influence movement:
    • brain
    • spinal cord
    • sensory input

    Spinal motor neurons control the limb muscles.
    They are the proximate generators of walking movements.
    They receive direct or indirect synaptic information via:

    • descending input from the brain,
    • sensory input from proprioreceptors and other receptors
    • local input from intrinsic spinal circuits

    Experiments on fish, salamanders, toads, turtles, cats, and other vertebrates has shown
    • The spinal cord contains a CPG for walking movements.
    • The brain may initiate and modulate locomotion.
    • But the brain is not necessary for generating the repetitive locomotor patterns of walking.
    • Sensory feedback in the hindlimbs is also unnecessary for hindlimb stepping movements.

    Robot models of salamanders walk and swim like real salamanders when their artificial CPGs are activated in the same manner as in real salamanders.

    The spinal cord CPG mechanism is probably primitive to all vertebrates.

    Consider your own experience of walking across uneven terrain.

    • A CPG controls the basic walking pattern
    • Sensory feedback allows you to correct for uneven ground.
    • Usually.