1. Subcortical Motor Systems: Cerebellum & Basal Ganglia Lecture 21

2. Motor Loops n Cortex  Subcortex  Cortex  Spinal cord n Cerebellum l coordination of movement n Basal Ganglia l selection & initiation of voluntary movements ~

3. Cerebellum n Nonmotor functions - memory/language n Coordination of complex movements n Programs ballistic movements l no feedback during execution l direction, force, & timing n Motor learning l shift from conscious  unconscious ~

4. Cerebellum: Anatomy n Folia & lobules l analogous to sulci & gyri n Vermis - along midline l output  ventromedial pathway n Hemispheres l output  lateral pathway n Deep cerebellar nuclei l analogous to thalamus ~

5. Motor Loop Through Cerebellum n Lateral cerebellum simplest circuit l 20 million axons n Cortex  pons & cerebellum l Prefrontal, Motor, PPC n Pons & Cerebellum  thalamus l VLc - ventrolateral nucleus n VLc  M1  lateral pathway ~

6. PrefrontalPPCM1M2 Pons, Cerebellum VLc Distal Limbs Lateral Cerebellar Motor Loop

7. Cerebellum: Damage n Lesions - loss of motor coordination n Dysynergia l no simultaneous movement of joints serial movement only n Dysmetric movements l to wrong coordinates n Alcohol intoxiction l depression of cerebellar circuits ~

8. Basal Ganglia n Caudate nucleus Putamen Globus Pallidus n Substantia Nigra l Tegmentum n Control slow movements l Using immediate sensory feedback ~ Striatum

9. Globus Pallidus Substantia Nigra Thalamus

10. Cross section of Tegmentum Substantia Nigra

11. PrefrontalPPCM1M2 Basal Ganglia VLo Distal Limbs Basal Ganglia Motor Loop

12. Basal Ganglia Movement Disorders

13. Parkinson’s Disease n 1% of population n Nigrostriatal pathway l Substantia nigra neurons die l Progressive loss n Hypokinesia l Rigidity l Bradykinesia l Akinesia ~

14. SMA Putamen - Globus Pallidus (GP i ) - Substantia Nigra + VLo Subthalamic Nucleus + Cortex + X Parkinson’s Disease +

15. Parkinson’s Disease: Treatment n Basal Ganglia - Cholinergic n Substantia Nigra - Dopaminergic n Drug Therapy l L-DOPA n Pallidectomy n Tissue transplants ~

16. Huntington’s Disease (Chorea) n Rare l onset 30-40s early as 20s n Degeneration of Striatum l Caudate l Putamen n GABA & ACh neurons ~

17. Symptoms n Khoros = dance n Uncontrollable, jerky movements n Dementia n Progressive eventually fatal ~

18. SMA Putamen - - + VLo Subthalamic Nucleus + X Huntington’s Disease GP i GP e - +

19. Huntington’s Disease: Cause n Genetic disorder n Single dominant gene on chromosome 4 n HD mutation - unstable trinucleotide repeat - CAG n # of repeats correlated w/ age of onset ~

20. n HD gene  huntingtin n 3 forms l mutated form binds to protein l involved in energy production l neuron starves n Excitotoxicity contributes to degeneration l glutamate  Nitric oxide (NO) l Potential treatment:: Inhibit NO synthase ~ Huntington’s Disease: Cause

21. Hyperkinesia n Excessive movement n Ballism l violent, flinging movements n Lesions in subthalamus l less inhibition of VLo l excitation of SMA ~

22. SMA Striatum - Globus Pallidus - + VLo Subthalamic Nucleus + X Hyperkinesia (e.g. ballism)