Basal Ganglia

1. Basal Ganglia NBIO 401 – Friday November 1, 2013

2. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • - Be able to describe the type of learning in which the basal ganglia are involved.

3. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • - Be able to describe the type of learning in which the basal ganglia are involved.

4. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • - Be able to describe the type of learning in which the basal ganglia are involved.

5. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • - Be able to describe the type of learning in which the basal ganglia are involved.

6. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • -Be able to describe the type of learning in which the basal ganglia are involved.

7. Objectives: • Be able to describe the anatomical components of the basal ganglia and their position in the brain relative to the cerebral cortex, internal capsule, and thalamus. • Be able to describe how the components of the basal ganglia are connected to the cerebral cortex and to each other. • Be able to explain the general effects of the direct and indirect pathways through the basal ganglia on movement. • Be able to describe the effect of the substantia pars compacta on the direct and indirect pathways. • Be able to explain how, in addition to the pathways affecting limb movements, there are other loops between the basal ganglia and cerebral cortex that perform analogous functions for oculomotor, executive, and emotional systems. • - Be able to describe the type of learning in which the basal ganglia are involved.

8. Basal Ganglia Position in the Brain

13. Striatum = Caudate & Putamen

15. Substantia Nigra Pars Reticulata (like GPi) Pars Compacta (dopamine source) Input Nuclei (caudate, putamen) Intermediate Nuclei (external globus pallidus, subthalamic nucleus) Output Nuclei (internal globus pallidus, substantia nigra pars reticulata)

16. Basal Ganglia Functional Organization

17. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Subthalamic nucleus

18. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Subthalamic nucleus

19. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

20. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

21. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

22. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

23. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

24. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

25. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Direct Pathway: Increases motor output Indirect Pathway: Decreases motor output Subthalamic nucleus

26. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Dopamine increases direct pathway activity Dopamine decreases indirect pathway activity Subthalamic nucleus

27. Basal Ganglia Diseases

28. Parkinson’s Disease

29. Functional organization of the Basal Ganglia Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum X Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Dopamine increases direct pathway activity Dopamine decreases indirect pathway activity Subthalamic nucleus

30. Parkinson’s Disease Caused By SNc Damage Cortex Motor Cortex Direct pathway Indirect pathway dopamine dopamine Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Subthalamic nucleus

31. Parkinson’s disease

32. Healthy / L-DOPA treatmentParkinson’s Disease

33. Healthy / L-DOPA treatmentParkinson’s Disease

34. Parkinson's Disease Gait

35. Parkinson’s Disease Caused By SNc Damage Cortex Motor Cortex Direct pathway Indirect pathway dopamine dopamine Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Subthalamic nucleus

36. Pallidotomy Lehman et al, Acta Neurochir (2000) 142-319

38. Parkinson’s Disease Caused SNc Damage Cortex Motor Cortex Direct pathway Indirect pathway Basal Ganglia Striatum Substantia nigra pars compacta D1 D2 Thalamus Direct Pathway (decreases inhibition of thalamus) Indirect Pathway (increases inhibition of thalamus) Globus pallidus external Excitatory Globus pallidus Internal & substantia nigra pars reticulata Inhibitory Loss of dopamine decreases movement via both direct and indirect pathways. Subthalamic nucleus

39. Cortex Motor Cortex Striatum D2 D1 Substantia nigra pars compacta Basal Ganglia Thalamus Globus pallidus external Globus pallidus internal/ substantia nigra pars reticulata Huntington’s Disease Subthalamic nucleus Preferential degeneration of neurons in D2 expressing medium spiny neurons in the striatum that are the start of the indirect pathway.

40. Huntington’s Disease

41. Cortex Motor Cortex X Striatum D1 D2 Substantia nigra pars compacta Basal Ganglia Thalamus Globus pallidus external Globus pallidus internal/ substantia nigra pars reticulata Huntington’s Disease Subthalamic nucleus Preferential degeneration of indirect pathway

42. Huntington’s disease Degeneration of MSNs in Striatum (Indirect pathway MSNs die first)

45. Basal Ganglia Other Loops & Learning

47. Striatum mediates associative learning (pairing one thing with another, stimulus-response, reward, etc.) and procedural learning (motor patterns, development of habits and skills), but not spatial learning (absolute location, mental maps of space) which is mediated by the hippocampus (along with declarative memory).

48. ende