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84 Cards in this Set
- Front
- Back
Where is Glutamate used in the basal ganglia circuits?
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-Cortex
-Subthalamic nucleus -Thalamus |
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Where is GABA used in the basal ganglia circuits?
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-Striatum
-Globus Pallidus |
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Where is Dopamine used in the basal ganglia circuits?
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from Substantia nigra pars compacta
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Is dopamine excitatory or inhibitory?
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It depends on what receptor it binds.
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What happens when dopamine binds D1 receptors?
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Excitatory - increases cAMP
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What happens when dopamine binds D2 receptors?
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Inhibitory - decreases cAMP
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Where are the D1 and D2 receptors?
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On the striatum
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4 circuits in the Basal Ganglia:
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1. Skeletomotor
2. Oculomotor 3. Prefrontal 4. Limbic |
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Where do the Skeletomotor circuits project? What is the function at each place?
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-Motor cortex - for execution of movement
-Premotor/SMA - for preparation for movement |
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Where does the oculomotor circuit project?
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To frontal and supplementary eye fields
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Where does the Prefrontal circuit project?
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-Prefrontal cortex
-LATERAL orbitofrontal cortex |
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Where does the Limbic circuit project?
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-Anterior cingulate gyrus
-MEDIAL orbitofrontal cortex |
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What are the 2 pathways involved in the skeletomotor circuit?
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1. Direct pathway
2. Indirect pathway |
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What is the net effect of the
-Direct pathway -Indirect pathway |
Direct = disinhibition of the thalamus; facilitates movement
Indirect = inhibition of the thalamus; inhibits movement |
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What is the purpose of the direct pathway?
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To reinforce motor patterns that have been selected - the go-ahead and keep doing it.
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What is the purpose of the indirect pathway?
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To brake movement and suppress it because motor programs or patterns selected are conflicting.
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What do the direct and indirect pathways combined do?
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Adjust the size and speed of signals that are telling our muscles to move.
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3 general functions of the Basal Ganglia:
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-Motor
-Eye movements -Cognitive |
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3 types of Motor functions:
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-Modulation of movement
-Sensorimotor integration -Initiation of internally generated movements |
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3 types of Cognitive functions of the basal ganglia:
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-Memory/spatial orientation
-Executive planning -Emotion |
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What does disruption of basal ganglia circuits impair?
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Autonomic (unconscious) execution of learned motor plans
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What is Hyperkinesis?
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Involuntary movements and tremors
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What is Hypokinesis?
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Muscle rigidity
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4 types of hyperkinesis:
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-Athetosis
-Ballismus -Chorea -Dystonia |
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What is athetosis?
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The combination of Chorea and dystonia - snakelike movements.
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what is ballismus?
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Flailing limbs
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What is chorea?
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Fidgeting
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What is dystonia?
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abnormal tone?
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4 examples of diseases that disrupt basal ganglia function:
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-Parkinson's
-Huntington's -Hemibalism -Behavioral disorders |
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What causes Parkinson's disease?
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Degeneration of Substantia nigra pars compacta dopaminergic neurons.
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What pathway in the basal ganglia circuits is affected by the loss of dopaminergic neurons in Parkinson's?
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The DIRECT pathway
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What is the Net effect of losing the direct pathway?
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Overactivity of the INDIRECT pathway - not enough excitation of the premotor and SMA cortex.
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So what is the pathophysiology of Parkinson's?
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Dopamine deficiency
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What causes Parkinson's?
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Unknown
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How much of your SNc do you have to lose before symptoms?
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A lot - maybe up to 70%
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What part of the brain is specifically overexcited in Parkinson's disease, and hence a surgical target?
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GPi
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4 cardinal signs of PD:
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-Resting tremor
-Rigidity -Bradykinesia -Postural instability |
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What is Bradykinesia?
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Reduced speed and amplitude of movements
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Where do the symptoms appear in the body of a PD patient?
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Unilaterally at onset; remain that way throughout the course.
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What is the gold-standard treatment (medicine) for PD?
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Levodopa
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What is levodopa?
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A drug that increases Dopamine
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What are 2 other meds that can be used to treat PD?
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-ACh decreasing drugs
-Glutamate blockers |
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What is the surgical target for treating PD?
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-GPi
-Subthalamic nucleus |
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What is the goal of lesioning or stimulating either GPi or the subthalamic nucleus to treat PD?
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To reduce the indirect pathway
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2 bad side effects of Levodopa:
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-Motor fluctuations
-Dyskinesia |
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What is the main problem in Huntington's disease?
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Selective loss of striatal medium spiny neurons.
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Why are striatal medium spiny neurons important?
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They make GABA
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What is the pathway effected by loss of GABA?
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The indirect pathway
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What is the net effect of degeneration of the indirect pathway EARLY in the disease?
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Excessive excitation of the premotor cortex and SMA
-Too much gas -Not enough brakes |
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What happens later in the disease of Huntington's?
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Loss of the DIRECT pathway so LESS MOVEMENT.
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So Huntington's pathology:
-Early -Late |
Early - too much movement
Late - not enough movement |
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What other type of Huntington's just sees not enough movement b/c of loss of direct pathway?
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Juvenile
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5 Cardinal signs of Early Parkinson's disease:
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-Athetosis
-Ballism -Chorea -Dystonia -Depression |
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What is athetosis?
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Slow writhing of extremities
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What is dystonia?
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Sustained muscle contractions like a stone
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What family had lots of hungtingtons?
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Ecuador
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What are the 3 cardinal symptoms of Late Huntington's disease?
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-Bradykinesia
-Rigidity -Dementia |
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What CAUSES huntington's?
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A genetic abnormality
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What is the inheritance of Huntington's?
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Autosomal dominant
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What is the genetic abnormality causing Huntington's?
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CAG repeats on chromosome 4 that encodes for the Huntingtin gene.
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What does the genetic abnormality do to proteins?
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Makes them accumulate in nuclei of neurons and apoptose.
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What is an indication of the age of disease onset?
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Length of CAG repeats
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What happens to the age of disease onset as Huntington's is passed down thru generations?
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CAG repeats increase in size, so the disease onset occurs earlier and earlier.
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Treatment for Huntington's disease:
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D2 receptor blockers - to activate the indirect pathway.
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What is Hemiballism?
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High amplitude flailing movement of an extremity.
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What is the cause of hemiballism?
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A stroke of the subthalamic nucleus
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What pathway is affected by a stroke of the subthalamic nucleus?
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The indirect pathway - not enough inhibition of mvment.
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How is hemiballism treated?
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It is very refractory to txmt
-D2 receptor blockers might help |
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What is dystonia? What are 2 subtypes?
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Sustained muscle contractions or spasms produce twisting and repetitive mvmts
-tonic -spasmodic |
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What are 3 things that can aggrevate dystonia?
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-Purposeful action
-Stress -Fatigue |
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What does the fact that dystonia is task specific show?
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That remapping of the brain occurs and specific areas of the cortex are over-excited.
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What can help reduce dystonia?
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A sensory trick like touching the jaw or something.
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What are 2 ways of classifying dystonia?
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-Based on location or body distribution
-Based on cause |
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5 types of dystonia based on location:
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-Focal
-Segmental -Multifocal -Generalized -Hemidystonia |
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What would be segmental dystonia?
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Dystonia of 2 contiguous body parts
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what is hemidystonia?
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Dystonia of half the body
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2 types of dystonia based on cause:
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-Idiopathic/primary
-Symptomatic/secondary |
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what is symptomatic dystonia?
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Dystonia caused by a known brain pathology
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What is blepharospasm?
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Involuntary eye blinking
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What is oromandibular dystonia?
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Involuntary jaw spasms or lower face/tongue spasms
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What is Meige syndrome?
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Oromandibular and blepharospasm combined (jaw/mouth/eye blinks)
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What is spasmodic dysphonia?
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Involuntary spasms of the vocal cords
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What is spasmodic torticollis?
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Involuntary head and neck spasms
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What type of dystonia is exemplified by Writer's Cramp?
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Task specific dystonia
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