Subcortical Motor Systems: Cerebellum & Basal Ganglia Lecture 21

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

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 ~

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 ~

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 ~

PrefrontalPPCM1M2 Pons, Cerebellum VLc Distal Limbs Lateral Cerebellar Motor Loop

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 ~

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

Globus Pallidus Substantia Nigra Thalamus

Cross section of Tegmentum Substantia Nigra

PrefrontalPPCM1M2 Basal Ganglia VLo Distal Limbs Basal Ganglia Motor Loop

Basal Ganglia Movement Disorders

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 ~

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

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

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 ~

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

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

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 ~

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

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

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