Term
What is the action of the basal ganglia (striatum)?
What is the main and secondary inputs to the striatum and what neurotransmitters are used? |
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Definition
Striatum= caudate and putamen
Modulation of goal directed voluntary movements starts with premotor planning (motor cortex)
-Prefrontal cortex is the main input to the striatum (uses glutamate, excitatory)
-Second input is the substantia nigra pars compacta in the midbrain (uses dopamine)
- Also gets acetylcholine input |
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Term
Where are dopamine receptors within the basal ganglia?
What else does this area do? |
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Definition
Substantia nigra pars reticulata
Also coordinates eye movements via a tract from the caudate -> pars reticulata -> superior colliculus |
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Term
| What are the main thalamic nuclei associated with the basal ganglia? |
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Definition
| Ventral Anterior and Lateral (VA/VL) |
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Term
| ___ neurons are the main neurons of the striatum |
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Definition
spiny
called this because they have many dendrites for all the INPUTS to the basal ganglia
The large amounts of inputs to these dendrites to decrease the number of outputs (lots of data processing) = convergence |
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Term
| What is the main neurotransmitter output of the basal ganglia? What parts of the basal ganglia provide this outflow tract? |
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Definition
| GABA via the substantia nigra pars reticulata and internal segment of the globus pallidus |
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Term
| What are the main neurotransmitter inputs to the basal ganglia and where does each come from (3) |
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Definition
| Dopamine (from substantia nigra pars compacta in the midbrain), glutamate from cortex and thalamus, and acetylcholine inside from interneurons |
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Term
Describe the prefrontal loop of the basal ganglia (4 steps):
(___ -> ___ and ___ (not ___) -> ___ -> ___ and ___)
- What does damage to this cause?
- What is the normal function of this pathway? |
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Definition
Is the prefrontal/associative loop
From the dorsolateral frontal lobes -> striatum and caudate (not putamen) -> globus pallidus internus -> mediodorsal and ventral anterior nuclei
-Damage causes inhibition (this normally regulates behavior)
-This helps with fight or flight responses (to run away from something scary, etc) |
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Term
| Describe the direct pathway of the basal ganglia with neurotransmitters and activation/inhibition of each step (5 steps) |
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Definition
Cortex -> activates (with glutamate) striatum (caudate and putamen) -> inhibits (with GABA) GPi and substantia nigra reticulata-> normally inhibits (with GABA) the VA/VL thalamus but now cannot do that -> activates (with glutamate) cortex
Striatum Inhibits the inhibitor (GPi and SNr) to promote movement
Tonically active |
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Term
| Describe the indirect pathway of the basal ganglia with neurotransmitters excitatory/inhibitory of each step (5 steps) |
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Definition
Cortex-> activates (with glutatmate) striatum (Caudate and Putamen) -> inhibits (with GABA) GPe -> inhibits (with GABA) subthalamic nucleus (STN) -> activates (with glutamate) GPi and substantia nigra reticulata (SNr) -> inhibits (with GABA) VA/VL of the thalamus so less output to the cortex
STN promotes the inhibitor (GPi and SNr) to decrease movements
Tonically active |
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Term
| D2 from ___ acts on the ___ pathway to ___ movement |
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Definition
D2 from the substantia nigra pars compacta (SNc) inhibits the striatum (caudate and putamen) in the indirect pathway
Inhibiting the indirect pathway (which inihibits movement) ultimately promotes movement |
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Term
| D1 acts on the ___ pathway to ___ movement |
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Definition
| D1 activates the striatum (Caudate and Putamen) in the direct pathway to promote movement |
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Term
| Glutamate is a ___ receptor, acts ___ (fast/slow) |
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Definition
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Term
| Dopamine is a ___ receptor, acts ___ (fast/slow) |
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Definition
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Term
| Where along the neuron are the dopamine receptors in the substantia nigra pars reticulata? |
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Definition
| in the presynaptic terminal |
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Term
| Which form of dopamine is preferentially lost in Parkinson's? |
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Definition
D1 (from substantia nigra pars compacta)
This blocks the direct pathway |
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Term
What neurons are lost in Huntington's disease?
What pathway does this affect and how? |
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Definition
Loss of striatal GABAergic, enkephalin, and D2 neurons
Dysregulates indirect pathway more |
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Term
| What are the effects of carbidopa and levodopa, what is the MOA, and what are its side effects? |
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Definition
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Medication Name
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MOA
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NT effect
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Indication
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Side effects
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Levodopa
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Dopamine precursor
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Acts at D1 and D2 receptors
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bradykinesia
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Compulsive behavior, hyperkinetic, psychosis, on-off phenomenon
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Carbidopa
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Inhibits peripheral metabolism of levodopa
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Inhibits DOPA decarboxylase which converts dopamine to serotonin
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Prolongs effect of levodopa
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See above
GI upset
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Term
| Which anti psychotic has the least D2 antagonism? |
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Definition
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Term
What is the MOA of ropinirole?
What's it used for? |
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Definition
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Ropinirole
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Dopamine agonist. (D2, D3, and D4 receptor agonist with highest affinity for D2)
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Inhibits indirect pathway (acts on striatum)
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Parkinsons, restless legs syndrome, extrapyramidal symptoms
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Term
What is the MOA of Benztropine?
What's it used for? |
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Definition
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Benztropine (Cogentin)
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anticholinergic
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Selective M1 muscarinic acetylcholine receptor binding (competitive binding against acetylcholine) (increases availability of dopamine by blocking its reuptake)
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Parkinsons, dystonia. Reduces extrapyramidal side effects of antipsychotic treatment. Second line for Parkinsons, improved tremor and rigidity
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Term
What's the MOA of Selegiline/ Rasagiline?
What's it used for?
What's a main side effect? |
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Definition
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Selegiline / rasagiline
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MAO B inhibitors.
Reduces degradation of dopamine in an irreversible fashion and prevents reuptake
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(MAO-B metabolizes dopamine)
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Parkinson’s (as an adjunct only or early on in the disease, because have to have dopamine for it to work), depression
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serotonin syndrome
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Term
What's the MOA of Tolcapone?
What's a side effect? |
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Definition
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Tolcapone (central) / entacapone (peripheral)
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COMT inhibitor
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Prevents methylation of levodopa by COMT in the periphery to prevent breakdown of dopamine
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Parkinsons, adjunct to carvidopa/levodopa
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Cannot combine with MAO inhibitor. Causes liver toxicity.
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Term
What's the MOA of typical antipsychotics?
How do you treat drug induced parkinsonism/tardive? |
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Definition
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Drug
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MOA
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Treatment
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Typical antipsychotics
(Haloperidol, chlorpromazine, etc)
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D2 receptor antagonism
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Benztropine (anticholinergic)- for Parkinsonism
Benadryl for tardive
Clonazepam (promotes GABA, decreases movement)
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Term
What's the MOA of second generation antipsychotics?
How do you treat drug induced parkinsonism/tardive? |
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Definition
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Second generation antipsychotics
(Risperidone, aripripazole)
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D1 and D2 receptor antagonist
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Benztropine (anticholinergic)- for Parkinsonism
Benadryl for tardive
Clonazepam (promotes GABA, decreases movement)
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Term
What's the main medication for Huntington's?
What's its MOA?
How does it help? |
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Definition
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Drug
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MOA
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NT effect
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Side effects
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Tetrabenazine
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Reversible depletion of monamines (dopamine, serotonin, NE, and histamine) from nerve terminals by inhibiting their uptake into presynaptic vesicles
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Suppress chorea
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depression
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Term
Bilateral and symmetric globus pallidus hyperintentisities
- Cause
- Symptoms
- Pathophys |
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Definition
- Cause: carbon monoxide poisoning
- Symptoms: HA, dizzy, AMS, gait
- Pathophys: anoxic + interferes with mitochondrial oxidative phosphorylation and activates PMNs = brain lipid peroxidation |
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Term
Bilateral and symmetric Putamen hyperintentisities
- Cause
- Symptoms
- Pathophys |
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Definition
- Cause: methanol toxicity (see bilateral putamen hemorrhage on CT)
- Symptoms: nausea, optic neuropathy, abd pain, acidosis
- Pathophys: metabolized into formic acid which inhibits cytochrome oxidase causing hypoxia/necrosis, metabolic acidosis, optic nerve demyelination |
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Term
Bilateral and symmetric Globus pallidus hypointentisities
- Cause
- Symptoms
- Pathophys |
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Definition
PKAN, eye of the tiger
- AR mutation on PANK2 gene leads to iron deposition
- Child with parkinsonism, dystonia, dementia, night blindness, death
- Gene codes for pantothenate e kinase (for vitamin B5 metabolism) which is required for production of coenzyme A |
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Term
| Explain the pathophys of the hyperkinetic movements in Huntington's |
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Definition
| Loss of GABA and D2 in the indirect pathway |
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Term
| Explain the pathophys of the late hypokinetic movement of Huntington's disease |
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Definition
| loss of GABA in the direct pathway |
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Term
| Children with Huntington's present with ___ first |
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Definition
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Term
| What parts of the basal ganglia make up the striatum? |
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Definition
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Term
| What parts of the basal ganglia make up the lenticular nucleus? |
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Definition
| Globus pallidus and Putamen |
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Term
What two structures make up the striatum?
What does this form ventrally? |
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Definition
putamen and head of the caudate,
ventrally they fuse to form the nucleus accumbens for limbic cicuitry |
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Term
| Most cortical inputs to the striatum ___ and use ___ as a neurotransmitter |
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Definition
| excitatory, use glutamate |
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Term
Outputs from the basal ganglia come from ___ which controls ___ and from ___ which controls ___
Output pathways are ___ and use ___ neurotransmitter |
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Definition
From substantia nigra pars reticulata which controls head and neck
and
From the internal segment of the globus pallidus which controls the rest of the body
Are inhibitory and use GABA |
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Term
The main outputs from the basal ganglia travel to what nuclei of the thalamus?
Where do the other (non-main) outputs of the basal ganglia project to? (3) |
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Definition
Ventral anterior (VA) and anterior portion of the Ventral lateral (VL) nucleus
(the posterior portion of the VL receives input from the cerebellum)
Also to:
-Mediodorsal nucleus of thalamus for limbic pathway
-Reticular formation for reticulospinal tract
-Superior colliculus for tectospinal pathway |
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Term
| What two structures form the lentiform nucleus? |
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Definition
| The putamen and globus pallidus |
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Term
| The blood supply to the striatum and globus pallidus is from ____. Blood supply to medial globus pallidus is the ___. |
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Definition
Striatum and GP: lenticulostriate branches of MCA
Medial globus pallidus: ACA |
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Term
| Blood supply to the caudate head is by ___ which is a branch of ____ |
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Definition
| Recurrent artery of Hubner, branch of the ACA |
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