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Basal Ganglia Circuitry

Basal Ganglia Physiology
The direct & indirect pathways
Overall Circuitry
Key Structures
Connectivity
  • The thalamus excites the cerebral cortex, which stimulates the spinal motor neurons.
  • The cortex excites the striatum.
The Direct Pathway
Key Structures
  • The combined globus pallidus internal segment and the substantia nigra reticulata
    • GPi/STNr
Connectivity
  • The striatum (primarily the putamen) inhibits GPi/STNr.
  • GPi/STNr inhibits the thalamus.
The direct pathway is overall excitatory
The Indirect Pathway
Key Structures
  • The globus pallidus external segment - GPe
Connectivity
  • GPe is inhibited by the Striatum.
  • GPe inhibits GPi/STNr
The indirect pathway is overall inhibitory
Subthalamic nucleus
  • The Indirect Pathway via the subthalamic nucleus
Connectivity
  • The subthalamic nucleus excites GPi/STNr.
  • GPe inhibits the subthalamic nucleus
Indirect Pathway: Summary
  • Whether it is because of GPe inhibition of the GPi/STNr
  • OR because of GPe inhibition of the subthalamic nucleus,
  • The indirect pathway is always overall inhibitory.
Hemiballismus & Parkinson's disease
Hemiballismus
Clinical Correlation: Hemiballismus
  • When the subthalamic nucleus is selectively injured, patients develop a loss of motor inhibition on the side contralateral to the subthalamic nucleus lesion, they develop wild ballistic, flinging movements, called hemiballismus.
Parkinson's Disease
Clinical Correlation: Parkinson's disease
  • Substantia nigra compacta degeneration causes Parkinson's disease.
  • It is a disorder of slowness and asymmetric muscle rigidity, often associated with tremor.
Dopamine Receptors
  • The substantia nigra compacta releases dopamine.
  • The two most prominent dopamine (D) receptors in the striatum are:
    • The D1 receptor, which is part of the direct pathway and is excited by dopamine.
    • The D2 receptor, which is part of the indirect pathway and is inhibited by dopamine.
Dopamine
  • Dopamine from the substantia nigra compacta:
    • Excites the direct pathway
    • Inhibits the indirect pathway
Both effects promote movement
Corticostriatal Fibers
  • Many frontal-subcortical pathways project through the basal ganglia in addition to the motor pathways we have drawn.
  • Through the corticostriatal fibers — the Muratoff bundle and the external capsule — the cerebral cortex targets the striatum in a topographic manner.
  • These pathways help drive a multitude of processes, including emotional, behavioral, somatosensory, and cognitive functional modalities.
Anatomy of the direct and indirect pathways
The fields of Forel
Direct pathway comprises:
  • Ansa lenticularis
  • Lenticular fasciculus
  • Thalamic fasciculus
The indirect pathway comprises:
  • Subthalamic fasciculus
Fields of Forel
  • Field H lies medial to the subthalamic nucleus and inferior to the zona incerta.
  • Field H1 lies in between the thalamus and zona incerta
    • Medial to the zona incerta and inferolateral to the thalamus.
  • Field H2 lies lateral to the zona incerta and medial to the internal capsule.
Direct Pathway
  • The direct pathway fibers comprise the pallidothalamic pathways and emanate from the internal segment of the globus pallidus.
    • The ansa lenticularis projects inferomedially from the globus pallidus internal segment, courses beneath the subthalamic nucleus, then turns superiorly to pass through Field H and Field H1 to enter the thalamus.
    • The lenticular fasciculus projects from the internal segment of the globus pallidus across the internal capsule, through Field H2 and then Field H, and then superiorly through Field H1 to enter the thalamus.
    • Where the ansa lenticularis and the lenticular fasciculus run together in Field H1, they are collectively called the thalamic fasciculus (for further discussion of this, see the end of the chapter).
Indirect Pathway
  • The indirect pathway is subserved by the globus pallidus external segment projections, which involve the subthalamic nucleus and substantia nigra.
    • Via the subthalamic fasciculus, the external segment of the globus pallidus projects to the subthalamic nucleus, which projects back to the external segment of the globus pallidus and also to the internal segment of the globus pallidus.
    • The subthalamic nucleus also communicates with the substantia nigra.
    • The globus pallidus external segment projects to the substantia nigra, which projects fibers through Fields H and H1 to enter the thalamus.
Key DOPAMINERGIC PATHWAYS
Mesocortical Pathway
  • Projections from ventral tegmental area to prefrontal cortex.
  • Decreased activity from psychotropic agents reduces the positive (psychotic) symptoms of schizophrenia.
Mesolimbic Pathway
  • Projections from ventral tegmental area to forebrain (esp. nucleus accumbens in the basal forebrain).
  • Responsible for cognitive and emotional function.
  • Decreased activity from psychotropic agents reduce:
    • Cognitive/Executive function (dorsolateral)
    • Emotion/Affect (ventromedial)
Nigrostriatal Pathway
  • Projections from the substantia nigra to striatum (caudate and putamen).
  • Responsible for movement.
  • Decreased activity from psychotropic agents reduce movement: pseudoparkinsonism.
Tuberoinfundibular pathway
  • Projections from the hypothalamus to the pituitary gland.
    • The origins of the pathway are classically assigned to the periventricular and arcuate (infundibular) nuclei.
    • The termination within the pituitary gland is in the median eminence.
  • Responsible for prolactin release: prolactin is under tonic inhibition by dopamine.
  • Decreased activity from psychotropic agents reduces prolactin inhibition and results in prolactin release: gynecomastia, galactorrhea, amenorrhea, infertility, etc...