Basal Ganglia Study Notes

Overview of the Basal Ganglia

  • The basal ganglia is a group of nuclei in the brain involved in a variety of functions including motor control, learning, and reward processing.

Key Components of the Basal Ganglia

  • Composition:
    • Striatum
    • Globus Pallidus
    • External segment (GPe)
    • Internal segment (GPi)
    • Subthalamic nucleus
    • Substantia nigra
    • Pars compacta (SNc)
    • Pars reticulata (SNr)
    • Ventral tegmental area (VTA)

Functions and Characteristics

Motor Symptoms in Basal Ganglia Diseases

  • Several diseases associated with the basal ganglia present prominent motor symptoms:
    • Parkinson’s Disease:
    • A progressive neurological disease characterized by:
      • Hypokinetic motor symptoms such as slow movement, small handwriting, decreased facial expression, and difficulty with gait initiation and maintenance.
      • Degeneration of dopaminergic neurons in the substantia nigra compacta (SNc).
      • Non-motor symptoms include cognitive impairment and anxiety, associated with later loss of neurons in the VTA.
    • Hemiballism:
    • Characterized by large involuntary movements of proximal limbs.
    • Results from localized damage to the subthalamic nucleus, often due to a stroke.
    • Huntington’s Disease:
    • Involuntary movements of the whole body at the early stages, followed by reduced movements later.
    • Symptoms arise from damage to medium spiny neurons in the striatum.

Parallel Feedback Loops

  • The basal ganglia interact with the cortex through parallel feedback loops, which means:
    • The main input nucleus is the striatum, which projects to two output nuclei (GPi and SNr).
    • These output nuclei project to the thalamus, which sends feedback to the cortex.
    • Each part of the basal ganglia is involved in different functions related to body movement, eye movement, and the execution of executive functions and emotional regulation.

Circuits of the Basal Ganglia

  • The circuits within the basals ganglia show a significant bottleneck:
    • In mice, neuron counts indicate roughly equal numbers of cortical neurons projecting to the striatum and striatal neurons.
    • However, in primates, there are about ten times more cortical neurons projecting to the striatum than the striatal neurons available.
    • A substantial reduction in population size occurs from the striatum to its output nuclei by a factor of 2-3 orders of magnitude.

Neuronal Types in Basal Ganglia

  • The majority of neurons (95%) in the striatum are medium spiny neurons, which are primarily inhibitory and project to other nuclei.
  • A small fraction comprises cholinergic interneurons and GABAergic interneurons.
  • The subthalamic nucleus consists of excitatory neurons, receiving input from the cortex and thalamus, and relaying it to output nuclei.
  • Many projection neurons in the substantia nigra and VTA release dopamine, influencing their target neurons' activity based on receptor type (D1 or D2).
Direct and Indirect Pathways
  • The basal ganglia involve direct pathways that project to output nuclei, and indirect pathways that involve additional processing through the GPe:
    • D1 receptors are excited by dopamine and facilitate direct pathways.
    • D2 receptors are inhibited by dopamine and participate in indirect pathways.

Dopamine and Reward Prediction Error

  • Some neurons in the VTA signal reward prediction error, meaning:
    • They are tonically active, responding to unexpected rewards.
    • After learning a stimulus associated with a reward, they respond to the stimulus instead.
    • If an expected reward fails to materialize, these neurons cease their firing around the expected reward time.

Basal Ganglia's Role in Learning and Choice

  • The basal ganglia are involved in various aspects of learning, including:
    • Action selection: Facilitating the choice between competing actions to prevent interference.
    • Movement vigor: Fine-tuning the speed and force of movements based on context and expected rewards.
    • Learning functions related to reinforcement which are affected by the health of striatal connections.
    • Evidence suggests lesions in certain nuclei impair learning new actions while not hindering well-learned tasks.

Examples of Learning Involvement

  • Research indicates:
    • Inhibiting protein synthesis in the striatum disrupts learning of skilled movements in rats.
    • Learning walking on a rotarod in mice indicates changes in neural activity correlated with different learning phases, showing that striatal areas communicate distinctly with prefrontal and motor cortices.

Balancing Risk and Reward in Motor Choices

  • The dorsal striatum is associated with managing actions based on perceived risks and rewards. Studies show that altering specific pathways influences avoidance behaviors in exploratory contexts.