Three Steps underlying voluntary movement
- brain sends motor commands to motor neurons in the spinal cord
- Motor neurons in spinal cord release ACh at neuromuscular junction
- ACh binds to nicotinic ACh receptors on muscle fibre and trigger muscle contraction
Nicotinic ACh receptors
Respond to NT, Acetylcholine. At the neuromuscular junction they are the primary receptor in muscle responsible for muscle-nerve communication that controls muscle contraction.
Where are motor neurons found?
In the ventral horns of spinal cord
How does AP travel to muscle from spinal cord?
Through the ventral roots
Where is acetylcholine released? What does it do once released?
- At the neuromuscular junction
- Released ACh binds to receptors on muscle fibre causing postsynaptic potentials (PSPs) to arise (same rules of temporal and spatial summation apply) and trigger action potentials in muscle fibre
What type of receptor are Nicotinic ACh receptors?
nAChR receptors are ionotropic
What attaches muscle to bone?
Tendon
Muscles are…
a bundle of fibres called myofiber; each fibre is ONE cell with multiple DNA containing nuclei
Why do singular muscle fibres have multiple nuclei?
They are a product of cellular fusion
What is myofiber made of?
cylinder shaped bundles of protein polymers called myofibrils
What is myofibril composed of?
Each myofibril is composed of repeats of a functional unit called sarcomere
What is a key factor in muscle contraction?
The dynamic change in the structure of the protein polymers (myofibrils)
Sarcomere
Basic contractile unit that makes up myofibril. Each unit has a myosin (thick) and actin (thin) protein filament.
Where would you find myosin and actin?
These protein filaments are found in each sarcomere, which is found in myofibril which composes myofiber.
Breakdown of muscles
muscles –> myofiber –> myofibril –> sarcomere –> actin and myosin
Muscles contract when…
thick and thin filaments pass each other
What is the function of the tropomyosin complex?
In a resting state, the tropomyosin complex masks the myosin binding sites in the actin filaments so the myosin head cannot grab the actin fibre
What exposes the myosin binding sites on actin?
Binding of ACh to nACh receptors trigger APs in muscle fibre which causes release of Ca2+ from sarcoplasmic reticulum (storage for Ca2+). Calcium ion binds to troponin pulling tropomyosin to the side exposing binding sites.
What role does calcium play in muscle contraction?
calcium ions are released from sarcoplasmic reticulum and bind to troponin revealing the binding sites
What does the myosin head do when myosin binding sites are exposed? What does it do?
It binds to actin (grabs it) and the bending motion pulls on the actin filaments causing them to slide
one motor neuron can be responsible for…
multiple muscle contractions
Somatic Nervous System
Receives sensory info from sensory organs (skin, eyes, ears) and controls movement of skeletal muscles. Carries motor and sensory information both to and from the CNS.
Muscles contain what types of sensory nerves (also number)?
2 types: muscle spindle and golgi tendon
Afferent nerves
SENSORY NERVES - carry info from various body parts close to external environment to the CNS
Efferent nerves
MOTOR NERVES - carry info from CNS to the skeletal muscle
Muscle spindle
muscle fibre that report muscle length, composed of intrafusal muscle fibres
Intrafusal
skeletal muscle fibres that serve as specialized sensory organs that detect the amount and rate of change in length of a muscle
What innervates muscle spindle?
Mechanosensory axon terminals
Innervate
to supply with nerves
Knee-jerk reflex is an example of
a stretch reflex
How does knee-jerk reaction work?
- sudden stretch of a muscle causes stretching of muscle spindle fibres
- triggers depolarization of sensory nerves in the muscle spindle
- directly activates firing of spinal motor neurons leading to contraction of muscle –> thus leg moves
Are the neural circuits involved in pain and muscle stretches different?
Yes
Withdrawal reflex is an example of
pain reflex
How does withdrawal reflex work?
- Pain sent to spinal cord is captured by nociceptor fibres
- axon terminals of nociceptor fibres enter the dorsal horn and synapse on excitatory interneurons (relay neurons)
- Interneurons stimulate motor neurons, producing pain reflex movements
Golgi Tendon Organ
- found inside the tendon
- composed of collagen fibres
What is golgi tendon organ innervated by?
mechanosensory axon terminals
What happens to golgi tendon organs when a muscle contracts?
Tension on golgi tendon organ increases . Once a threshold tension is reached, AP is generated at golgi tendon which inhibits muscle contraction.
Function of golgi tendon organs
prevent muscle damage
Neuronal pathway involved in golgi tendon organs
AP is generated at golgi tendon organ and sensory nerve endings synapse on inhibitory interneurons in the spinal cord. The interneurons then inhibit motor neurons innervating the same muscle.
Spinal reflex movements do not…
involve neurons in the brain
Three cortical areas that control movement
Primary motor cortex, secondary motor cortex, and association cortex
What is the association cortex responsible for?
Integrating and evaluating external stimuli
What is the secondary motor cortex responsible for?
Plans the sequences of movements to perform tasks
What is the primary motor cortex responsible for?
Executing motor commands by innervating motor neurons in the spinal cord
Execution is to the primary motor cortex as planning is to the…?
secondary motor cortex
Parts of the association cortex that control movement
Posterior parietal and dorsolateral prefrontal association cortex
What is the posterior parietal association cortex responsible for?
Integrating visual, auditory, and somatosensory information from external objects and body parts (joints, muscles, etc)
Where does output from posterior parietal association cortex go?
to the dorsolateral prefrontal association cortex
What is the Dorsolateral Prefrontal Association Cortex responsible for?
evaluating external stimuli and initiating appropriate voluntary reactions
Where does output from the dorsolateral prefrontal cortex go?
to secondary motor cortex and primary motor cortex
Secondary motor cortex
Becomes active right before the initiation of a voluntary movement. Sends outputs to the primary motor cortex. Involved in planning movements.
Primary motor cortex
Located anterior to central fissure
How is the primary motor cortex similar to the somatosensory cortex?
Disproportionately larger areas are devoted to body parts that require complex movements (hands, mouth, tongue) than those requiring less precise motor control (trunk).
Two major pathways that motor commands to spinal motor neurons travel along?
dorsolateral pathway and ventromedial pathway
Dorsolateral pathway
- runs through the dorsolateral side of spinal cord
- controls distal muscles in arms, legs, hands, fingers, and toes
Distal and proximal muscles
- muscles farther from centre of body
- muscles closest to midline of body
Ventromedial pathway
- runs through the ventromedial side of spinal cord
- controls proximal muscles in trunk and proximal limbs
Pathways in the dorsolateral pathway
corticospinal tract and corticorubrospinal tract
Dorsolateral: Corticospinal tract
Controls wrist, hands, fingers, toes
Dorsolateral: Corticorubrospinal tract
Controls distal muscles of arms and legs (motor neurons of spinal cord) and some facial muscles (motor neurons in brainstem)
Describe pathway of neurons in dorsolateral corticospinal tract
- neurons in primary motor cortex directly synapse on motor neurons in the spinal cord
- cortical axons descend through medullary pyramids then move across midline
Describe pathway of neurons in dorsolateral corticorubrospinal tract
- Cortical neurons synapse at the red nucleus
- axons of red nucleus cross the midline at the level of the medulla and THEN synapse on motor neurons in the spinal cord AND some on motor neurons in brainstem
How does the ventromedial corticospinal tract descend?
Ipsilaterally, the axons branch and synapse bilaterally in multiple spinal segments
What does the ventromedial corticospinal tract control?
trunk and proximal limb muscles for goal-directed movements
Which pathway is in charge of goal-directed movements
the corticospinal tract of the ventromedial pathway
Tracts in the ventromedial pathway
corticospinal tract and cortico-brainstem-spinal
Describe pathway of the neurons in the cortico-brainstem-spinal tract
They synapse on various brainstem structures (vestibular nuclei, tectum, reticular formation) which then innervate multiple spinal segments
What does the cortico-brainstem spinal tract control?
body postures - adjusts trunk and proximal limb muscles in response to changes in sensory signals (vestibular, auditory, and visual)
Evaluation, planning, and execution
association cortex, secondary motor cortex, primary motor cortex
What’s the major driving force of voluntary movements
cortical inputs
Non-cortical structures that make voluntary movements more streamlined?
basal ganglia and cerebellum
What connects the secondary and primary cortex?
Secondary cortex sends signals to primary motor cortex through the basal ganglia and then the thalamic circuit
Structures that make up the basal ganglia
- striatum (which is made of caudate nucleus and putamen)
- globus pallidus (between striatum and thalamus, has interna and externa sections)
- substantia nigra (in the midbrain)
Substantia Nigra is a source of…
dopamine
Ventrolateral nuclei in the thalamus receive input from… and send…
- basal ganglia
- excitatory outputs to motor cortex
Which structures of the Basal Ganglia are GABAergic? What does it mean?
The striatum, globus pallidus interna (gp-i), globus pallidus externa (gp-e) are all GABAergic structures. This means they are inhibitory structures.
Inhibitory structures are…while excitatory structures are
- GABAergic
- glutamatergic
Which structure is not active when you are at rest?
secondary motor cortex (no motor commands)
What does it mean when globus pallidus is said to be tonically active? What does this activity do?
It means that it is continuously producing GABA which inhibits thalamic motor nuclei and prevents unnecessary movements
What holds back the motor thalamus when you are at rest?
GABA produced by the globus pallidus interna
What needs to occur for initiation of movements? What structure completes this function?
Tonic activity of gp-i must be inhibited. Striatum is activated by excitatory signals from secondary motor cortex and striatum then inhibits gp-i.
Which structures of the movement system are inhibitory and which are excitatory?
Inhib: Striatum and gp-i
Excit: Secondary motor cortex and thalamus
What is the “direct pathway of the Basal Ganglia”? What’s another name for it?
Direct pathway is from striatum to gp-i (inhibitory structure inhibiting inhibitory structure). Also called the D1 pathway.
How does the D1 pathway get its name?
Striatal GABA neurons express dopamine receptor type 1 (D1R)
What happens when D1R cells fire action potential spikes?
Movement is promoted because striatal neurons will inhibit gp-i
What would an inhibitory structure between the striatum and gp-i do if the striatum is activated? Which structure is this?
Inhibit movement. The globus pallidus externa.
What’s included in the indirect pathway of the basal ganglia? What’s another name for this pathway?
Striatum -> gp-e -> gp-i
Also called D2 pathway
How does D2 pathway get its name?
striatal GABA neurons express D2R receptors
Which dopamine receptors are associated with the GO and NO GO pathways?
D1R is GO, D2R is NO GO.
What type of receptors are DRs?
Metabotropic receptors
Neurons in the striatum express either…
D1R or D2R but not both—they are mutually exclusive.
D1R has an… while D2R has an…
excitatory effect
inhibitory effect
What role does dopamine play in the basal movement circuit?
Dopamine is required to inhibit the D2R pathway so that the direct pathway is functional. Glutamate alone from the cortex will activate both pathways.
Parkinson’s disease
The substantia nigra is degenerated—no dopamine or less.
Major inputs to the cerebellum
- input from the motor cortex via pons (info about motor commands)
- Input from the sensory and vestibular system (info about body position and movements)
What does the cerebellum do and how does it do it?
Compares motor commands and body position and then adjusts movements as they occur—fine tunes motor controls.
Cerebellum learns by…
sensory feedback