511-action

For fun

Output types

• What types of outputs are there?
• How are they produced?
  • By the muscles
  • By the nervous system
• Outputs include
  • Movements, vocalizations, facial expressions, gestures
  • Autonomic responses
  • Endocrine responses

Types of movements

https://medlineplus.gov/ency/images/ency/fullsize/17234.jpg

• Reflexes
  • Simple, highly stereotyped, unlearned, rapid, acquired early
• vs. Planned or voluntary actions
  • Complex, flexible, acquired, slower
• Discrete (reaching) vs. rhythmic (walking)
• Ballistic (no feedback) vs. controlled (feedback)

Motor system anatomy

Key ‘nodes’

• Primary motor cortex (M1)
• Non-primary motor cortex
• Basal ganglia
• Brain stem
• Cerebellum
• Spinal cord

Projection pathways

• Pyramidal tracts
  • Pyramidal cells (Cerebral Cortex Layer 5) in primary motor cortex (M1)
  • Corticobulbar (cortex -> brainstem) tract
  • Corticospinal (cortex -> spinal cord) tract
• Crossover (decussate) in medulla
  • L side of brain ennervates R side of body

https://commons.wikimedia.org/wiki/File:Gray764.png#/media/File:Gray764.png

Source: Wikipedia

• Extrapyramidal system
  • Tectospinal tract
  • Vestibulospinal tract
  • Reticulospinal tract
• Involuntary movements
  • Posture, balance, arousal

Muscles

• Generate forces

Functional classes

• Axial
  • Trunk, neck, hips
• Proximal
  • Shoulder/elbow, pelvis/knee
• Distal
  • Hands/fingers, feet/toes

Agonist/antagonist pairs

Anatomical types

• Cardiac
• Striated (striped)
  • Skeletal
  • Voluntary control, mostly connected to tendons and bones
• Smooth
  • Arteries, hair follicles, uterus, intestines
  • Regulated by ANS (involuntary)

How skeletal muscles contract

• Motoneuron (ventral horn of spinal cord)
• Projects to muscle fiber
• Neuromuscular junction
  • Synapse between motor neuron and muscle fiber
  • Releases ACh

• Motor endplate
  • Contains nicotinic ACh receptors
• Activation produces excitatory endplate potential
  • Muscle fibers depolarize
  • Depolarization spreads along fibers like an action potential
  • Sarcomeres are segments of fibers
  • Intramuscular stores release Ca++

• Muscle fibers contain bundles of myofibrils
• Myofibrils are organized into bundles called sarcomeres
• Myofibrils (w/in sarcomere)
  • Contain actin & mysosin proteins
  • “Molecular gears”
• Bind, move, unbind in presence of Ca++, adenosine triphosphate (ATP)

Skeletal muscle fiber types

• Fast twitch/fatiguing
  • Type II
  • White meat
• Slow twitch/fatiguing
  • Type I
  • Red meat

Muscles as sensory organs

Two fiber types

• Intrafusal fibers
  • Sense muscle length and change in length, e.g. “stretch”
  • Also called muscle spindles
  • Provide muscle proprioception (perception about the self, a form of interoception)
  • Ennervated by by primary Ia afferents (sensory output from muscle); also secondary Type II fibers
  • Ennervated by gamma (\(\gamma\)) motor neurons (motor input)
• Extrafusal fibers
  • Generate force
  • ennervated by alpha (\(\alpha\)) motor neurons

Monosynaptic stretch (myotatic) reflex

• Muscle stretched (length increases)
• Muscle spindle in intrafusal fiber activates
• Ia afferent sends signal to spinal cord
  • Activates alpha (\(\alpha\)) motor neuron
• Muscle contracts, shortens length

https://commons.wikimedia.org/wiki/File:Fusimotor_action.jpg#/media/File:Fusimotor_action.jpg

• Gamma (\(\gamma\)) motor neuron fires to take up ‘slack’ in intrafusal fiber

Why doesn’t antagonist muscle respond?

• Polysynaptic inhibition of antagonist muscle
• Prevents/dampens tremor

Speed of sensory information propagation

• Brain gets fast(est) propagating sensory info from spindles

Disorders of movement

• Parkinson’s
• Huntington’s

The Faces of Parkinson’s

• Slow, absent movement, resting tremor
• Cognitive deficits, depression
• DA Neurons in substantia nigra degenerate
• Treatments
  • DA agonists
  • DA agonists linked to impulse control disorders in ~1/7 patients (Ramirez-Zamora, Gee, Boyd, & Biller, 2016)
  • Levodopa (L-Dopa), DA precursor

Huntington’s

• Formerly Huntington’s Chorea
  • “Chorea” from Greek for “dance”
  • “Dance-like” pattern of involuntary movements
• Cognitive decline
• Genetic + environmental influences
• Disturbance in striatum
• No effective treatment
• But progress in an animal model targeting abnormal protein products (Li et al., 2019)

Clinical trial focused on gene therapy

https://clinicaltrials.gov/ct2/show/study/NCT03761849

The big picture

• Control of movement determined by multiple sources
• Cerebral cortex + basal ganglia + cerebellum + spinal circuits

The “real” reason for brains

What does motor cortex activity encode?

Muscle activity? Limb velocity? Or…?

Shenoy et al., 2013

What does the cerebellum do?

• Predict future sensory states? (Ito, 2008)

Systems perspective

• Cognitive/affective states
• Nervous system states
• Muscle states
• Actions
• Consequences of actions on world states
• Sensory states

(Powers, 1973)

(Powers, 1973)

(Powers, 1973)

https://www.nytimes.com/2019/10/23/well/move/something-in-the-way-we-move.html

References

Ito, M. (2008). Control of mental activities by internal models in the cerebellum. Nat. Rev. Neurosci., 9(4), 304–313. https://doi.org/10.1038/nrn2332

Li, Z., Wang, C., Wang, Z., Zhu, C., Li, J., Sha, T., … Lu, B. (2019). Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds. Nature, 575(7781), 203–209. https://doi.org/10.1038/s41586-019-1722-1

Powers, W. T. (1973). Behavior: The control of perception. Aldine Chicago. Retrieved from http://www.pctresources.com/Other/Reviews/BCP_book.pdf

Ramirez-Zamora, A., Gee, L., Boyd, J., & Biller, J. (2016). Treatment of impulse control disorders in parkinson’s disease: Practical considerations and future directions. Expert Rev. Neurother., 16(4), 389–399. https://doi.org/10.1586/14737175.2016.1158103