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84 Cards in this Set

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Where is Glutamate used in the basal ganglia circuits?
-Cortex
-Subthalamic nucleus
-Thalamus
Where is GABA used in the basal ganglia circuits?
-Striatum
-Globus Pallidus
Where is Dopamine used in the basal ganglia circuits?
from Substantia nigra pars compacta
Is dopamine excitatory or inhibitory?
It depends on what receptor it binds.
What happens when dopamine binds D1 receptors?
Excitatory - increases cAMP
What happens when dopamine binds D2 receptors?
Inhibitory - decreases cAMP
Where are the D1 and D2 receptors?
On the striatum
4 circuits in the Basal Ganglia:
1. Skeletomotor
2. Oculomotor
3. Prefrontal
4. Limbic
Where do the Skeletomotor circuits project? What is the function at each place?
-Motor cortex - for execution of movement
-Premotor/SMA - for preparation for movement
Where does the oculomotor circuit project?
To frontal and supplementary eye fields
Where does the Prefrontal circuit project?
-Prefrontal cortex
-LATERAL orbitofrontal cortex
Where does the Limbic circuit project?
-Anterior cingulate gyrus
-MEDIAL orbitofrontal cortex
What are the 2 pathways involved in the skeletomotor circuit?
1. Direct pathway
2. Indirect pathway
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
What is the purpose of the direct pathway?
To reinforce motor patterns that have been selected - the go-ahead and keep doing it.
What is the purpose of the indirect pathway?
To brake movement and suppress it because motor programs or patterns selected are conflicting.
What do the direct and indirect pathways combined do?
Adjust the size and speed of signals that are telling our muscles to move.
3 general functions of the Basal Ganglia:
-Motor
-Eye movements
-Cognitive
3 types of Motor functions:
-Modulation of movement
-Sensorimotor integration
-Initiation of internally generated movements
3 types of Cognitive functions of the basal ganglia:
-Memory/spatial orientation
-Executive planning
-Emotion
What does disruption of basal ganglia circuits impair?
Autonomic (unconscious) execution of learned motor plans
What is Hyperkinesis?
Involuntary movements and tremors
What is Hypokinesis?
Muscle rigidity
4 types of hyperkinesis:
-Athetosis
-Ballismus
-Chorea
-Dystonia
What is athetosis?
The combination of Chorea and dystonia - snakelike movements.
what is ballismus?
Flailing limbs
What is chorea?
Fidgeting
What is dystonia?
abnormal tone?
4 examples of diseases that disrupt basal ganglia function:
-Parkinson's
-Huntington's
-Hemibalism
-Behavioral disorders
What causes Parkinson's disease?
Degeneration of Substantia nigra pars compacta dopaminergic neurons.
What pathway in the basal ganglia circuits is affected by the loss of dopaminergic neurons in Parkinson's?
The DIRECT pathway
What is the Net effect of losing the direct pathway?
Overactivity of the INDIRECT pathway - not enough excitation of the premotor and SMA cortex.
So what is the pathophysiology of Parkinson's?
Dopamine deficiency
What causes Parkinson's?
Unknown
How much of your SNc do you have to lose before symptoms?
A lot - maybe up to 70%
What part of the brain is specifically overexcited in Parkinson's disease, and hence a surgical target?
GPi
4 cardinal signs of PD:
-Resting tremor
-Rigidity
-Bradykinesia
-Postural instability
What is Bradykinesia?
Reduced speed and amplitude of movements
Where do the symptoms appear in the body of a PD patient?
Unilaterally at onset; remain that way throughout the course.
What is the gold-standard treatment (medicine) for PD?
Levodopa
What is levodopa?
A drug that increases Dopamine
What are 2 other meds that can be used to treat PD?
-ACh decreasing drugs
-Glutamate blockers
What is the surgical target for treating PD?
-GPi
-Subthalamic nucleus
What is the goal of lesioning or stimulating either GPi or the subthalamic nucleus to treat PD?
To reduce the indirect pathway
2 bad side effects of Levodopa:
-Motor fluctuations
-Dyskinesia
What is the main problem in Huntington's disease?
Selective loss of striatal medium spiny neurons.
Why are striatal medium spiny neurons important?
They make GABA
What is the pathway effected by loss of GABA?
The indirect pathway
What is the net effect of degeneration of the indirect pathway EARLY in the disease?
Excessive excitation of the premotor cortex and SMA
-Too much gas
-Not enough brakes
What happens later in the disease of Huntington's?
Loss of the DIRECT pathway so LESS MOVEMENT.
So Huntington's pathology:
-Early
-Late
Early - too much movement

Late - not enough movement
What other type of Huntington's just sees not enough movement b/c of loss of direct pathway?
Juvenile
5 Cardinal signs of Early Parkinson's disease:
-Athetosis
-Ballism
-Chorea
-Dystonia
-Depression
What is athetosis?
Slow writhing of extremities
What is dystonia?
Sustained muscle contractions like a stone
What family had lots of hungtingtons?
Ecuador
What are the 3 cardinal symptoms of Late Huntington's disease?
-Bradykinesia
-Rigidity
-Dementia
What CAUSES huntington's?
A genetic abnormality
What is the inheritance of Huntington's?
Autosomal dominant
What is the genetic abnormality causing Huntington's?
CAG repeats on chromosome 4 that encodes for the Huntingtin gene.
What does the genetic abnormality do to proteins?
Makes them accumulate in nuclei of neurons and apoptose.
What is an indication of the age of disease onset?
Length of CAG repeats
What happens to the age of disease onset as Huntington's is passed down thru generations?
CAG repeats increase in size, so the disease onset occurs earlier and earlier.
Treatment for Huntington's disease:
D2 receptor blockers - to activate the indirect pathway.
What is Hemiballism?
High amplitude flailing movement of an extremity.
What is the cause of hemiballism?
A stroke of the subthalamic nucleus
What pathway is affected by a stroke of the subthalamic nucleus?
The indirect pathway - not enough inhibition of mvment.
How is hemiballism treated?
It is very refractory to txmt
-D2 receptor blockers might help
What is dystonia? What are 2 subtypes?
Sustained muscle contractions or spasms produce twisting and repetitive mvmts
-tonic
-spasmodic
What are 3 things that can aggrevate dystonia?
-Purposeful action
-Stress
-Fatigue
What does the fact that dystonia is task specific show?
That remapping of the brain occurs and specific areas of the cortex are over-excited.
What can help reduce dystonia?
A sensory trick like touching the jaw or something.
What are 2 ways of classifying dystonia?
-Based on location or body distribution
-Based on cause
5 types of dystonia based on location:
-Focal
-Segmental
-Multifocal
-Generalized
-Hemidystonia
What would be segmental dystonia?
Dystonia of 2 contiguous body parts
what is hemidystonia?
Dystonia of half the body
2 types of dystonia based on cause:
-Idiopathic/primary
-Symptomatic/secondary
what is symptomatic dystonia?
Dystonia caused by a known brain pathology
What is blepharospasm?
Involuntary eye blinking
What is oromandibular dystonia?
Involuntary jaw spasms or lower face/tongue spasms
What is Meige syndrome?
Oromandibular and blepharospasm combined (jaw/mouth/eye blinks)
What is spasmodic dysphonia?
Involuntary spasms of the vocal cords
What is spasmodic torticollis?
Involuntary head and neck spasms
What type of dystonia is exemplified by Writer's Cramp?
Task specific dystonia