1 / 69

Basal Ganglia

D. Basal Ganglia. Neural structures involved in the control of movement. Basal Ganglia. Key take-home messages: - Components of the basal ganglia - Function of the basal ganglia - Functional circuitry of the basal ganglia e.g., direct and indirect pathways, transmitters

zoe
Download Presentation

Basal Ganglia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. D Basal Ganglia

  2. Neural structures involved in the control of movement

  3. Basal Ganglia Key take-home messages: - Components of the basal ganglia - Function of the basal ganglia - Functional circuitry of the basal ganglia e.g., direct and indirect pathways, transmitters - Circuitry involved in movement disorders discussed

  4. Basal Ganglia • Neostriatum • Caudate nucleus • Putamen • Ventral striatum (nucleus accumbens) 2.Paleostriatum Globus pallidus external segment (GPe) Globus pallidus internal segment (GPi) 3. Substantia Nigra Pars compacta (SNc) Pars reticulata (SNr) 4. Subthalamic nucleus (STN)

  5. What do the basal ganglia do? • Basal ganglia are involved in generation of • goal-directed voluntary movements: • Motor learning • Motor pattern selection

  6. Location in human brain From Neuroscience, Purves et al. eds., 2001

  7. Forebrain Midbrain

  8. Forebrain Input to basal ganglia Midbrain

  9. Regions of cortical input to the basal ganglia (blue) Lateral view Medial view

  10. Output to thalamus and cortex Forebrain Midbrain

  11. Neurons of the basal ganglia

  12. Synaptic input to and output from striatal medium spiny neurons Smith and Bolam 1990

  13. Medium spiny neuron projections

  14. Basal ganglia loops • Convergence • large dendritic trees • of striatal output neurons (medium spiny neurons) dendritic spines

  15. Cortex GPe Striatum GPi/SNr Basal ganglia loops 150,000,000 • Convergence • large dendritic trees • decreasing cell number 500:1 30,000 300:1 100 100:1 1

  16. Prefrontal loop (Associative) Limbic loop Basal ganglia loops – motor and non-motor Motor loop

  17. Input Output and internal circuitry

  18. *tonically active ~100 Hz GPi/SNr * GPe STN VA/VL Cortex Direct pathway Striatum Excitation (glutamate) Inhibition (GABA) * Modified from Wichmann and Delong, Curr Opin Neurobiol. 6:751-758, 1996.

  19. Disinhibition *tonically active ~100 Hz * GPi/SNr GPe STN VA/VL Cortex Direct pathway Direct pathway: facilitates movement Striatum Excitation (glutamate) Inhibition (GABA) * Brain stem/ Spinal cord Modified from Wichmann and Delong, Curr Opin Neurobiol. 6:751-758, 1996.

  20. Patterns of activity when glutamate is applied in striatum

  21. Patterns of activity during motor behavior

  22. Excitation (glutamate) Striatum *tonically active ~100 Hz * GPi/SNr GPe STN VA/VL Cortex Inhibition (GABA) Indirect pathway: inhibits movement Indirect pathway * Disinhibition Brain stem/ Spinal cord Modified from Wichmann and Delong, Curr Opin Neurobiol. 6:751-758, 1996.

  23. D2 SNc Excitation (glutamate) D1 Striatum *tonically active ~100 Hz GPi/SNr * GPe STN VA/VL Cortex Inhibition (GABA) Direct pathway: facilitates movement Indirect pathway: inhibits movement * Brain stem/ Spinal cord Modified from Wichmann and Delong, Curr Opin Neurobiol. 6:751-758, 1996.

  24. Direct and indirect pathways in mouse brain Gerfen Nat. Neurosci. 2006

  25. Patch-matrix compartmental organization of corticostriatal and striatonigral pathways Corticostriatal neurons deep in layer V provide -> patches Superficial layer V neurons -> matrix. Patch MSNs -> DAergic neurons in SNc Matrix MSNs -> GABAergic neurons in SNr Gerfen TINS 1992

  26. Patch-matrix organization of corticostriatal and striatonigral pathways Gerfen TINS 1992

  27. Ionotropic versus metabotropic R R 2nd messenger metabotropic ionotropic

  28. Dopamine Ionotropic versus metabotropic Glutamate R R 2nd messenger metabotropic ionotropic

  29. glu DA Direct transmission vs. modulation R EPSP Direct transmission

  30. glu DA Direct transmission vs. modulation No direct effect of DA

  31. glu DA Direct transmission vs. modulation Striatal medium spiny neuron enhanced or diminished response R D1-Rs in the direct pathway: 1) increase GluR phosphorylation 2) alters ionic conductances to amplify cortical input Modulation

  32. glu DA Direct transmission vs. modulation Striatal medium spiny neuron enhanced or diminished response R D2-Rs in the indirect pathway: 1) increase GluR phosphorylation 2) alters ionic conductances to dampen cortical input Modulation

  33. Direct pathway

  34. Release of DA in substantia nigra, as well as in striatum is required for control of movement by the basal ganglia

  35. Somaticrelease (Jaffe et al. 1998) Dendritic release (Geffen et al. 1976; Rice et al. 1994) SNc DA cell Synaptic DA release in striatum Somatodendritic DA release in SNc modified from Fallon et al. 1978 Smith and Bolam 1990

  36. DA neuron Striatonigral axon terminal (direct pathway) SNc GABA SNr SNr output neurons (GABAergic, tonically active, project to thalamus) are inhibited by the direct, striatonigral pathway, leading to disinhibitionof the thalamus and facilitationof movement

  37. DA neuron Striatonigral axon terminal (direct pathway) SNc GABA Presynaptic D1 dopamine receptors enhance striatonigral GABA release SNr

  38. DA neuron Striatonigral axon terminal (direct pathway) Somatodendritic dopamine SNc GABA Presynaptic D1 dopamine receptors enhance striatonigral GABA release SNr Somatodendritic DA release, therefore, enhances the effect of the direct striatonigral pathway to facilitate movement

  39. Direct and indirect pathways

  40. Motor behavior is determined by the balance between direct/indirect striatal outputs • Hypokinetic disorders • insufficient direct pathway output • excess indirect pathway output • Hyperkinetic disorders • excess directpathwayoutput • insufficient indirectpathway output

  41. Pope John Paul II Michael J. Fox Muhammad Ali Janet Reno Katherine Hepburn SNc Parkinson’s disease • Pathophysiology • Primary: loss of nigrostriatal DA projection Striatum

  42. Human midbrain Parkinson’s disease Normal

  43. Parkinson’s disease

  44. Parkinson’s disease Symptoms • Motoric • Tremor (~4-5 Hz, resting) • Bradykinesia • Rigidity • Loss of postural reflexes • Depression • Dementia

  45. Parkinson’s disease Tremor (~4-5 Hz, resting) All video clips are from Movement Disorders in Clinical Practice, Guy Swale, Ed., Isis Medical Media, Oxford, 1998.

  46. Parkinson’s disease Bradykinesia

  47. Parkinson’s disease Loss of postural reflexes …even with mild tremor and bradykinesia

More Related