Lecture 18 - Basal Ganglia

Learning objectives

• Describe the neuroanatomical connections to and from the basal ganglia.

• Describe the neural circuitry within the basal ganglia.

• Determine how dopamine modulates basal ganglia circuits.

• Differentiate between movement disorders of the basal ganglia.

Basal ganglia

• Modulate movements by regulating upper motor neuronal circuits

• Subcortical nuclei, including the caudate, putamen, and globus pallidus

  • Associated with substantia nigra and subthalamic nucleus of the ventral thalamus

• Form a subcortical loop that links most of cerebral cortex with upper motor neurons in motor and premotor cortices

Inputs to basal ganglia

• Input zone is the striatum = caudate + putamen

  • Aka corpus striatum, meaning “striped body”

• Cortical input from association areas in frontal and parietal lobes, as well as temporal, insular, and cingulate cortices

  • Corticostriatal pathway

• Caudate input is association cortices and motor areas that control eyes

• Putamen input is somatosensory, visual, premotor and motor, and auditory

Basal ganglia circuitry

• Striatal neurons that receive axonal input called medium spiny neurons (MSNs)

  • Large dendritic trees allow them to collect and integrate input from cortical, thalamic, and brainstem structures

• Axons from MSNs converge in the pallidum = globus pallidus + substantia nigra pars reticulata

  • Output of the basal ganglia 

• MSNs also receive input from local axon collaterals, local circuit interneurons, thalamic neurons, and dopaminergic neurons from substantia nigra pars compacta

Output from basal ganglia

• MSNs are GABAergic

  • Terminate in globus pallidus (GP) and substantia nigra pars reticulata (SNr)

• Neurons in internal segment of GP affect motor cortex via a relay in the ventral anterior and ventral nuclei of the thalamus

• SNr neurons synapse on neurons in superior colliculus to influence head and eye movements

  • No thalamic relay

• Output neurons from GP and SNr are GABAergic

  • Tonically inhibit thalamus and superior colliculus

• MSNs induce GABAergic inhibition of tonically active GABAergic cell of GP and SNr → excitation of upper motor neurons

  • I.e., disinhibition allows upper motor neurons to send commands to initiate voluntary movement

Direct and indirect pathways

• MSN projections to internal segment of GP is direct pathway

  • Release thalamic neurons from inhibition to drive upper motor neurons for volitional movements

• Indirect pathway involves MSN projections to external segment of GP

  • GP neurons project to internal segment and subthalamic nucleus

  • Subthalamic nucleus also receives cortical inputs

  • Indirect pathway antagonizes direct pathway, allows for focused selection of motor program

Dopaminergic modulation

• Recall that D1 receptors increase cAMP and D2 receptors decrease cAMP

  • D1 receptor activation enhances excitatory input from cortex 

  • D2 receptor activation suppresses input from cortex

• Contributes to reward-related modulation of behavior

Parkinson’s disease

• Characterized by tremor, slowness of movement, rigidity of extremities, minimal facial expressions, and sometimes dementia

• Onset age 50-70, death in 10-20 years

• Degeneration of dopaminergic projections from substantia nigra pars compacta (A)

  • Results in increased inhibition of VA/VL thalamic nuclei, thus decreasing frontal cortex output (B)

Huntington’s disease

• Characterized by progressive increase in jerking muscle movements and defects in behavior and cognition

• Onset age is 40-50, with death in 10-20 years

• Degeneration of MSN projections to external segment of GP, resulting in atrophy (A)

  • Results in decreased inhibition of VA/VL thalamic nuclei, thus increasing frontal cortex output (B)