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Basal Ganglia

Basal Ganglia. basal ganglia. recall: major DA targets, involved in movement & motivation. BG Disorders. In humans, basal ganglia dysfunction associated with both hypokinetic and hyperkinetic movement disorders Hypokinetic Hyperkinetic akinesia chorea bradykinesia ballism

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Basal Ganglia

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  1. Basal Ganglia

  2. basal ganglia • recall: major DA targets, involved in movement & motivation

  3. BG Disorders In humans, basal ganglia dysfunction associated with both hypokinetic and hyperkinetic movement disorders HypokineticHyperkinetic akinesia chorea bradykinesia ballism rigidity tics

  4. A Parkinson’s Brainstem

  5. Parkinson’s disease • Progressive death of dopamine neurons • Hypokinetic disorder (also tremor) • Treated with dopamine precursor (L-Dopa) or agonists • Movie

  6. Huntington’s disease • Progressive death of striatal spiny neurons • Hyperkinetic disorder: chorea • Similar problems from subthalamic nucleus lesions, also Tourette’s, OCD • Treated with dopamine blockade disease: striatal degeneration healthy

  7. Medium spiny neurons • Principal neuron type in striatum • Recipient of corticostriatal inputs • Extensive dendrites – each receives input from 10,000 fibers • Unusual: GABAergic (inhibitory) projections • Also collaterals (competitive network? for competition based on value?)

  8. Striasomes/Patch Matrix

  9. The corticostriatal projection • Input nucleus of basal ganglia: striatum • topographic projection from entire cortex (including sensory, motor, associative areas) • ultimately reciprocated • also dopamine Voorn et al 2004

  10. Parkinson’s disease • Progressive death of dopamine neurons • Hypokinetic disorder (also tremor) • Treated with dopamine precursor (L-Dopa) or agonists • Movie

  11. Huntington’s disease • Progressive death of striatal spiny neurons • Hyperkinetic disorder: chorea • Similar problems from subthalamic nucleus lesions, also Tourette’s, OCD • Treated with dopamine blockade disease: striatal degeneration healthy

  12. Parkinson’s treatment • Suggested by model, STN lesions (primates) & GPi lesions in humans alleviate PD symptoms • huge success of animal research, modeling • More recently, turned to reversible/tunable deep brain (STN) stimulation (DeLong 1990)

  13. Deep-brain stimulation for PD • Target subthalamic nucleus (usually) • High frequency rhythmic stimulation • Mechanism not entirely clear

  14. Model of BG disorders • hypokinetic & hyperkinetic disorders caused by imbalance in direct/indirect pathways (Arbin et al. 1989; Alexander & Crutcher 1990) • Dopamine excites striatal MSNs projecting to direct pathway and inhibits those projecting to indirect pathway (this is an oversimplification) (DeLong 1990)

  15. Model of BG disorders • hypokinetic & hyperkinetic disorders caused by imbalance in direct/indirect pathways (Arbin et al. 1989; Alexander & Crutcher 1990) • Dopamine excites striatal MSNs projecting to direct pathway and inhibits those projecting to indirect pathway (this is an oversimplification) Hypokinetic (Parkinson’s) Hyperkinetic (Huntington’s) (DeLong 1990) (DeLong 1990)

  16. The Dopamine Revolution

  17. A Parkinson’s Brainstem

  18. Dopamine responses • Burst to unexpected reward • Response transfers to reward predictors • Pause at time of omitted reward Schultz et al. 1997

  19. The Standard Model Reward Prediction Error Q(t+1) = Q(t) + α[r(t+1) - Q(t)] Q(t) = Estimate of EU at t r = Reward on last trial

  20. Bush and Mosteller New Association Strength Old Association Strength = + Correction

  21. Bush and Mosteller New Value Estimate Old Value Estimate = + Correction Old Value Estimate Obtained Reward Correction = -

  22. Bush and Mosteller Association Strength 1 2 3 4 5 6 7 8 9 10 Trial Number

  23. More dopamine responses reward following 0% predictive cue reward following 50% predictive cue reward following 100% predictive cue no reward following 100% predictive cue (Fiorillo et al 2003)

  24. Bayer and Glimcher, 2005, 2007

  25. Neuronal Population N=44

  26. RPE in Humans: Specific model RPE = outcome ($) – lottery expected value ($)

  27. n = 12 subjects, 3003 trials random effects

  28. Basal ganglia • “Loop” organization • Input (from cortex): striatum • Output (back to cortex, via thalamus): globus pallidus (internal)

  29. Direct and indirect pathways • Parallel paths through BG • Opposite effects on thalamus, motor ctx • direct pathway has 2x inhibition: net facilitation, “go” • indirect pathway has 3x inhibition: net inhibition, “no-go” • Recordings: • Striatum: excitation & inhibition related to movement execution • GPi: inhibition related to movement execution • Why have two pathways? Alexander & Crutcher 1990

  30. Striatal PANs

  31. Post-Saccadic Neurons: • Class 1: Movement Just Completed • Class 2: Reward Just Received

  32. Qi(t) Coded Before Movement • Qchosen(t) Coded After Movement Lau and Glimcher, 2009

  33. Dopamine and plasticity • If dopamine carries a prediction error, where does learning happen? • Potentially, the cortico-striatal synapse

  34. DA and corticostriatal plasticity Wickens et al. 1996 • Three-factor learning rule? (pre/post/dopamine) • wi,t+1 = wi,t + edt

  35. Addiction

  36. If it is: The Standard RPE Model + Addiction (Redish) Q(t+1) = Q(t) + α[r(t+1) - Q(t)] +D D = Dopamine Activation r = Reward on last trial

  37. Oculomotor matching task:Searching for Action Values Choice 0.10 0.20 Cues Fix Rewards arranged using independent reward probabilities

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