Lecture 5: Basal Ganglia & Cerebellum

Voluntary Motor System

• Movement requires balance between activation + inhibition

• Basal ganglia: inhibits movement initiation

• Cerebellum: predicts and adjusts ongoing movements

• Voluntary action means suppressing alternative actions that are inappropriate to goal achievement.

Basal Ganglia

• Set of structures below cortex (5 structures connected to each other)

• Inhibits the motor cortex

• Prevents unwanted/competing movements

• To initiate action, basal ganglia inhibition must be turned off.

Neurotransmitters

• Glutamate: excitatory

• GABA: inhibitory

• Basal ganglia mainly inhibitory

Dopamine & Substantia Nigra

• Dopamine involved in movement, motivation, mood, decision-making

• Originates from Substantia nigra:

  • Midbrain structure

  • Collection of cell bodies that synthesize and release dopamine.

• No dopamine neurons in the cortex, just the midbrain

• Main target to release dopamine is the basal ganglia

• Dopamine reduces basal ganglia inhibition of motor cortex

• Substantia neurons have to be activated

• When dopamine goes to the basal ganglia, that’s what causes the “brake” that inhibits the motor cortex.

Initiating Action

1. Premotor cortex activates

2. Dopamine released

3. Basal ganglia inhibition reduced

4. Motor cortex initiates movement

Parkinson’s Disease

• Loss of dopamine neurons in substantia nigra and VTA

• Dopamine neurons do not regenerate

• Inhibition remains active (nothing to stimulate basal ganglia to trigger brake)

• Movement initiation difficult

• Core feature: freezing

• Starting a movement is hard, so they freeze

• Treatments:

  • Levo-Dopa (L-Dopa): 

• Synthesized in the brain to become dopamine.

• Replaces low dopamine levels in patients. 

• Restores movement initiation. 

• Long-term use = dyskinesia (tremor and uncontrolled movements)

• Deep brain stimulation of basal ganglia sub-region

• Removes basal ganglia inhibition on motor system

Huntington’s Disease

• Genetic degeneration of basal ganglia neurons

• Loss of inhibition

• Motor cortex overactive

• Choreiform movement (cannot stop moving)

• No cure

• Experimental treatment: gene therapy, CRISPR (way of editing a genome, removing copies of the gene).

Comparison

• Parkinson’s: too little movement

• Huntington’s: too much movement

Cerebellum

• ~20 billion neurons

• Receives sensory + motor input

• Sends output to motor areas

• Does not initiate movement

• Smooths, coordinates, fine-tunes

Forward Model

• Predicts outcome of motor command

• Compares predicted vs actual movement

• Uses visual + proprioceptive feedback

• Makes real-time corrections

Cerebellar Ataxia

• Poor coordination

• Clumsy, unsteady, poorly timed movements

• Initiation intact but inaccurate