Term
| The collective term basal ganglia refers to (gray/white) matter deep to the cortex |
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Definition
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Term
| What 6 basal ganglia nuclei are discussed in lecture? |
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Definition
caudate nucleus
putamen
globus pallidus
substantia nigra
subthalamic nucleus
nucleus accumbens |
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Term
| caudate + putamen = ______ |
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Definition
| striatum ("striped body") |
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Term
| putamen + globus pallidus = _______ |
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Definition
lenticular nucleus
(aka lentiform nucleus) |
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Term
| the globus pallidus is divided into how many regions? What are they? |
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Definition
| 2 regions - externa and interna |
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Term
| which basal ganglia nucleus is situated next to the lateral ventricles? |
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Definition
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Term
| The main input into the basal ganglia is from the __1___. The basal ganglia sends output to the ___2___. ___2___ then sends info back to ___1___. |
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Definition
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Term
| What are the 4 major parallel pathways in of the basal ganglia? |
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Definition
1. motor loop
2. executive loop
3. limbic loop
4. eye movement loop |
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Term
| The motor loop of the basal ganglia controls the ____ and the ____ of movement |
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Definition
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Term
| the direct pathway (increases/decreases) inhibitory basal ganglia output. |
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Definition
decreases
(Direct Decreases inhibitory)
(IN-direct IN-creases INhibitory) |
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Term
| the indirect pathway (increases/decreases) inhibitory basal ganglia output |
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Definition
increases
(Direct Decreases inhibitory)
(IN-direct IN-creases INhibitory; Indirect Inhibits movement)) |
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Term
| What is the path of the Direct pathway of the basal ganglia (includes 4 nuclei/locations) |
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Definition
| Cortex > putamen > Globus Pallidus interna > VA/VL (Ventral Anterior/ Ventral Lateral of Thalamus > cortex |
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Term
| what are the 2 neuron types (based upon which neurotransmitters they release) in the Direct pathway? |
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Definition
| Neurons that release glutamate and neurons that release GABA. |
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Term
In the Direct Pathway, the neuron from the cortex to the putamen is (excitatory/inhibitory).
- putamen to Globus Pallidus interna?
- Globus Pallidus interna to Thalamus?
- Thalamus to cortex? |
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Definition
cortex to putamen - excitatory
putamen to globus pallidus interna - inhibitory
globus pallidus internato thalamus - inhibitory
thalamus to cortex - excitatory
** overall Direct Decreases inhibitory (promotes movement) |
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Term
| the direct pathway (promotes/inhibits) movement |
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Definition
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Term
| neurons from putamen are also called ____ neurons |
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Definition
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Term
| What is the path of the indirect pathway of the basal ganglia? |
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Definition
| cortex > putamen > globus pallidus externa > Subthalamic Nucleus > GPi > thalamus > cortex |
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Term
In the indirect pathway, the neuron from the cortex to the putamen is (excitatory/inhibitory)
- putamen to globus pallidus externa?
- globus pallidus externa to subthalamic nuclei?
- subthalamic nuclei to GPi?
- GPi to thalamus? |
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Definition
cortex to putamen - excitatory
putamen to globus pallidus externa - inhibitory
GPe to subthalamic nuclei - inhibitory
STN to GPi - excitatory
GPi to thalamus - inhibitory
** overall (IN-direct IN-creases INhibitory; Indirect Inhibits movement) |
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Term
| the indirect pathway (promotes/inhibits) movement |
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Definition
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Term
| the ______ regulates direct and indirect pathways through dopamine |
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Definition
| substantia nigra pars compacta |
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Term
| Which dopamine receptors stimulate adenylate cyclase? |
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Definition
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Term
| which dopamine receptors inhibit adenylate cyclase? |
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Definition
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Term
| D1 receptors are associated with the (direct/indirect) pathway |
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Definition
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Term
| D2 receptors are associated with the (direct/indirect) pathway |
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Definition
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Term
| release of Dopamine (activates/inhibits) the direct pathway and (activates/inhibits) the indirect pathway |
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Definition
| activates the direct pathway and inhibits the indirect pathway |
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Term
| overall, release of dopamine (promotes/inhibits) movement |
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Definition
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Term
| 65yo male presents with tremor that started in right arm. His handwriting has become less legible and smaller. He also notes that he has difficulty with buttons. His wife notes that when he walks his right arm doesn’t swing much. Over time the tremor has spread to involve other limbs. He displays rest tremors and bradykinesia. What does this patient have? |
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Definition
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Term
| what is the KEY pathology of Parkinson's disease? |
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Definition
| loss of dopamine cells in the substantia nigra |
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Term
| what is a classical pathological feature of Parkinson's seen histologically? |
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Definition
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Term
| What are the key motor features of Parkinson's? |
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Definition
Rest tremor
bradykinesia
rigidity
gait imbalance
masked facies |
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Term
| What are the key non-motor features of Parkinson's? |
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Definition
Autonomic dysfuntion - hypotension, constipation, sexual dysfunction
cognitive impairment
sleep disorders
depression/anxiety |
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Term
| are motor features or non-motor features in Parkinson's due to dopamine loss? |
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Definition
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Term
T or F
In Parkinson's, the loss of dopamine release to D1 receptors will eventually lead to less inhibition of the inhibitory GPi neurons |
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Definition
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Term
| what are some risk factors for Parkinson's Disease? |
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Definition
Older age
male gender
rural living
well water
pesticide exposure
head trauma |
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Term
| What are 3 protective factors for Parkinson's |
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Definition
smoking
caffeine
high uric acid levels |
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Term
| What was the 1st gene identified to cause Parkinson's when mutated? |
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Definition
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Term
| where is alpha synuclein found in Parkinson's disease? |
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Definition
| in lewy bodies (overproduction) |
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Term
| where is Parkinson's believed to start (what level of the brain) |
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Definition
| brainstem - medulla and olfactory system |
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Term
| What are the very first symptoms of Parkinson's? |
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Definition
loss of sense of smell
constipation
sleep disturbance
depression |
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Term
T or F
It is thought that the tendency for alpha-synuclein to form aggregates contributes to the pathology of Parkinson's? |
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Definition
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Term
| What gene has been linked to young onset Parkinson's? |
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Definition
| Parkin (autosomal recessive) |
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Term
| Most common gene associated with Parkinson's? Accounts for __% of all Parkinson's cases? |
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Definition
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Term
T or F
Increased kinase activity in LRRK-2 mutations is hypothesized to cause toxicity |
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Definition
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Term
T or F
A single genetic or environmental cause is likely in most cases of PD |
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Definition
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Term
| What are 4 types of drugs used in Parkinson's treatment? |
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Definition
L-dopa
Dopamine receptor agonists
Monoamine oxidase inhibitors
COMT inhibitors |
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Term
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Definition
(tyrosine hydroxylase) (aromatic amino acid decarboxylase)
Tyrosine ----------------------->L-Dopa----------------------->Dopamine
...Dopamine released into synapse...
(monoamine oxidase) (catechol-o-methyl-transferase)
Dopamine------------------>DOPAC------------------------->HVA
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Term
| Why give L-Dopa instead of just dopamine? |
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Definition
| L-Dopa crosses the BBB, whereas dopamine does not |
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Term
T or F
The quick metabolization of AADC (Aromatic Amino acid decarboxylase-*such as L-Dopa*) peripherally can cause side effects such as nausea and hypotension |
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Definition
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Term
| what is taken with L-Dopa to avoid nausea and hypotension? |
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Definition
| an AADC inhibitor (carbidopa) |
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Term
| Taking L-Dopa for long periods of time can lead to what side effects? |
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Definition
dyskinesias
wearing-off, delayed-on, dose failures |
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Term
| COMT inhibitors include these 2 |
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Definition
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Term
| how do COMT inhibitors work? |
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Definition
| COMT breaks down dopamine in the synapse…COMT inhibitors inhibit this breakdown and allow more Dopamine to be taken up. Peripherally, more L-Dopa is allowed to get to the brain |
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Term
| which COMT inhibitor is used most? |
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Definition
entacapone
--tolcapone rarely causes liver toxicity |
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Term
| What are 2 MAO inhibitors? |
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Definition
|
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Term
| what are 3 dopamine receptor agonists? |
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Definition
| prmipexole, ropinirole, rotigotine |
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Term
| What're the advantages of receptor agonists? |
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Definition
Delay onset of motor complications
Much less likely to cause dyskinesias
Help reduce wearing off |
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Term
| what other drugs can help tremors in Parkinson's? |
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Definition
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Term
| What other drugs can help dyskinesias? |
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Definition
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