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What is the Basal Ganglia? A Journey into the Deep Nuclei

What is the Basal Ganglia? A Journey into the Deep Nuclei. Overview. Anatomy Loops & Pathways Motor Disorders Research Info. 1. 1. 1. 1. Components of the Basal Ganglia. Input Nuclei Corpus Striatum (aka Striatum) Caudate Putamen Output Nuclei Globus Pallidus Interna

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What is the Basal Ganglia? A Journey into the Deep Nuclei

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  1. What is the Basal Ganglia?A Journey into the Deep Nuclei

  2. Overview • Anatomy • Loops & Pathways • Motor Disorders • Research Info 1 1 1 1

  3. Components of the Basal Ganglia • Input Nuclei • Corpus Striatum (aka Striatum) • Caudate • Putamen • Output Nuclei • Globus Pallidus Interna • Substantia Nigra Pars Reticulata* • Intermediate Nuclei • Globus Pallidus Externa • Subthalamic Nucleus* • Substantia Nigra Pars Compacta*

  4. Anatomy of the Basal Ganglia

  5. Striatal Input and Output 1 1

  6. Topography of Striatum

  7. Functions of the Basal Ganglia • Non-Motor Loops • Executive/Prefrontal Loop • Limbic Loop • Oculomotor Loop • Motor Loop (Focus of our journey) • Regulation of upper motor neurons • Necessary for normal initiation

  8. Pathways of Motor Loop • Direct Pathway • Overall Excitatory • Indirect Pathway • Overall Inhibitory WARNING: Gross-oversimplification of material is contained throughout this presentation. Proceed with caution!

  9. Direct Pathway(aka the Express Route) CORTEX PUTAMEN (GPe) (STN) GP interna VA/VL THALAMUS Glutamate (+) GABA (-) Glutamate (+) GABA (-)

  10. Indirect Pathway (aka, scenic route) CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS Glutamate (+) GABA (-) GABA (-) Glutamate (+) Glutamate (+) GABA (-)

  11. What is missing? • Effect of DA on pathways • Direct Pathway: Stimulates • Indirect Pathway: Inhibits • Overall Excitatory

  12. DA in Direct Pathway Dopamine (+) Substantia Nigra pars compacta

  13. DA in the Indirect Pathway Dopamine(-) Substantia Nigra pars compacta

  14. Direct and Indirect Motor Loops CORTEX PUTAMEN (GPe) (STN) GP interna VA/VL THALAMUS CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS Glutamate (+) Glutamate (+) (+) (--) DA GABA (-) GABA (-) GABA (-) Glu(+) Glu(+) Glutamate (+) GABA (-) GABA (-)

  15. How do I keep this all straight? • Basal Ganglia (Caudate, Putamen, and GP) • Medium Spiny neurons = GABAergic • GABA = Inhibitory • Cortex, Thalamus, STN • Here, looking at Glutamatergic neurons • Glut=excitatory • Dopamine from Substantia Nigra pc • Acts on Putamen

  16. Movement Disorders • Hyperkinetic • Hemiballismus • Huntington’s Disease • Hypokinetic • Parkinson’s Disease • Drug Induced (Neuroleptics, MPTP)

  17. Hemiballismus CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS + Glutamate (+) GABA (-) GABA (-) Glutamate (+) Glutamate (+) GABA (-)

  18. Hemiballismus • Injury usually to STN • Decreased inhibition (Indirect Pathway) • Characterized by uncontrolled flinging • TX: Dopamine Antagonist http://www.neuroanatomy.wisc.edu/grossvideo/hemiballismus.asf Where was the lesion?

  19. Huntington’s Disease

  20. Huntington’s Disease CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS + Glutamate (+) GABA (-) GABA (-) Glutamate (+) Glutamate (+) GABA (-)

  21. Parkinson’s Disease • Loss of DA neurons in substantia nigra • Four cardinal symptoms • Bradykinesia, Akinesia, Rigidity, Tremor http://www.neuroanatomy.wisc.edu/grossvideo/neuroclips.html

  22. Parkinson’s Disease CORTEX PUTAMEN (GPe) (STN) GP interna VA/VL THALAMUS CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS Glutamate (+) Glutamate (+) (+) (--) DA GABA (-) GABA (-) GABA (-) Glu(+) Glu(+) Glutamate (+) GABA (-) GABA (-)

  23. Research Team • MPTP animal model • Surgical Techniques for inactivation of STN or GP interna • Pallidotomy • Deep Brain Stimulation

  24. Animal Model • MPTP • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine • Selectively toxic to DA neurons in SN • Monkeys treated with MPTP (Bergman, Wichman, &Delong, J Neurophys 1994) • Tremor • Increased STN activity • Increased GPi activity

  25. Pallidotomy • Permanent • Unilateral • Radio-frequency lesion • MRI and CT sterotactic localization • Micro-electrode recording for localization • Improvement in “OFF” period, not “ON” • No change l-dopa dosage • Risk of hemiballismus

  26. Pallidotomy Lehman et al,Acta Neurochir(200) 142-319

  27. Subthalamic Stimulation • Adjustable, Reversible • Can be used bilaterally • Localized • by MRI or CT • physiologically by coordinated firing and tremor • Improvement in “OFF”, Some “ON” • Reduction in l-dopa dosage ***Current therapies do not stop progression of disease, they treat the symptoms

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