2020-11-10 09:36:02

Prelude

Prelude

Announcements

  • Exam 3 next Tuesday, November 17
  • Grading
    • Best 3 of 4 quizzes
    • Best 3 of 4 exams
    • Blogs or paper

Today’s Topics

  • Wrap-up on pain
  • The neuroscience of action

Pain

Pain in the brain

Pain in the brain

“…we used machine-learning analyses to identify a pattern of fMRI activity across brain regions — a neurologic signature — that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other areas…”

(Wager et al., 2013)

Pain relief

  • Prostaglandins
    • hormone-like effects, but released in many places
    • trigger vasodilation and inflammation

Pain relief

  • Paracetymol (acetaminophen)
    • Mechanism not fully understood
    • inhibits synthesis of prostaglandins via cyclooxygenase (COX) enzyme
    • may modulate endocannabinoid system
  • Nonsteroidal anti-inflamatory drugs (NSAIDs): aspirin, ibuprofen
    • Also inhibit prostaglandins via COX

Pain relief

  • Opioids
    • Activate endogenous opioid systems
    • multiple receptor types (\(\delta\), \(\kappa\), \(\mu\),…)
    • peripheral sensory neurons, amygdala, hypothalamus, PAG, spinal cord, cortex, medulla, pons,…
    • brainstem opioid neurons provide descending inhibition of nociceptors

Pain relief

Pain relief

  • Why rubbing can help

Gate control theory (Melzack & Wall, 1965)

Gate control theory (Melzack & Wall, 1965)

Psychological and physical dimensions

Summary

  • Pain
    • Multiple receptor channels
    • Highly interconnected CNS network
    • Multiple targets for modulation

Action

The neuroscience of action

  • What types of actions are there?
  • How are they produced?
    • By the muscles
    • By the nervous system

Remember

  • Nervous system “output” includes
    • Movements
    • Autonomic responses
    • Endocrine responses

Types of actions

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

Multiple, parallel controllers

Key “nodes” in network

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

Muscle classes

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

Muscles

Muscle types

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

Muscle types

How skeletal muscles contract

  • Motoneuron (ventral horn of spinal cord)
  • Neuromuscular junction
    • Releases ACh

From spinal cord to muscle

How skeletal muscles contract

  • Motor endplate
    • Contains nicotinic ACh receptor
    • Generates…
  • Excitatory endplate potential
    • Muscle fibers depolarize
    • Depolarization spreads along fibers like an action potential
    • Sarcomeres are segments of fibers
    • Intramuscular storage sites release Ca++

Motor endplate

How skeletal muscles contract

  • Myofibrils (w/in sarcomere)
    • Actin & mysosin proteins
    • “Molecular gears”
  • Bind, move, unbind in presence of Ca++ pllus energy source (ATP)

Anatomy of muscle fibers

Anatomy of motor endplate

Agonist/antagonist muscle pairs

Meat preference?

Muscle fiber types

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

Muscles are sensory organs, too!

Two muscle fiber types

Two muscle fiber types

  • Intrafusal fibers
    • Sense length/tension
    • Contain muscle spindles linked to Ia afferents
    • ennervated by gamma (\(\gamma\)) motor neurons
  • 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

Monosynaptic stetch (myotatic) reflex

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

https://www.nytimes.com/2020/11/09/sports/emily-harrington-free-climb-yosemite.html

Monosynaptic stretch (myotatic) reflex

Why doesn’t antagonist muscle respond?

Why doesn’t antagonist muscle respond?

  • Polysynaptic inhibition of antagonist muscle
  • Prevents/dampens tremor

Brain gets fast(est) sensory info from spindles

How the brain controls the muscles

  • Pyramidal system
    • Pyramidal cells (from 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

Corticospinal tract

How the brain controls the muscles

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

Extrapyramidal system

Disorders

  • Parkinson’s
  • Huntington’s

The Faces of Parkinson’s

Parkinson’s

  • Slow, absent movement, resting tremor
  • Cognitive deficits, depression
  • DA Neurons in substantia nigra degenerate
  • Treatments

Huntington’s

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

Huntington’s

Final thoughts

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

Next time…

  • Vision
  • Review for Exam 3

References

Borbiro, I., Badheka, D., & Rohacs, T. (2015). Activation of TRPV1 channels inhibits mechanosensitive piezo channel activity by depleting membrane phosphoinositides. Sci. Signal., 8(363), ra15. https://doi.org/10.1126/scisignal.2005667

Melzack, R., & Wall, P. D. (1965). Pain mechanisms: A new theory. Science, 150(3699), 971–979. https://doi.org/10.1126/science.150.3699.971

Papini, M. R., Fuchs, P. N., & Torres, C. (2015). Behavioral neuroscience of psychological pain. Neurosci. Biobehav. Rev., 48, 53–69. https://doi.org/10.1016/j.neubiorev.2014.11.012

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 Review of Neurotherapeutics, 16(4), 389–399. https://doi.org/10.1586/14737175.2016.1158103

Wager, T. D., Atlas, L. Y., Lindquist, M. A., Roy, M., Woo, C.-W., & Kross, E. (2013). An fMRI-based neurologic signature of physical pain. N. Engl. J. Med., 368(15), 1388–1397. https://doi.org/10.1056/NEJMoa1204471