Week 1: dopaminergic system Flashcards
1
Q
What are the three parts of the brain stem?
A
- mesencephalon / midbrain
- pons (”bridge”)
- medulla (oblongata)
2
Q
What is the medulla (oblongata)?
A
- a part of the brain stem
- looks like a thicker continuation of the spinal cord
- contains vital centers for circulation and respiration
- decussation (=Kreuzung) of the pyramidal tract
3
Q
What is the pons?
A
- a part of the brain stem
- connected to the cerebellum by thick fiber tracks (peduncles)
- unpaired basilar artery at the base (ventral aspect) → blood supply to vital brain stem structures
4
Q
What is the mesencephalon?
A
- a part of the brain stem
- also called “midbrain”
- dorsal side: consists of the quadrigeminal plate with superior and inferior colliculi
- ventral side: consists of cerebral peduncles with the substantia nigra
5
Q
What are the Cranial Nerves?
A
- 12 nerves on each side of the brain
- have brainstem as target or source
- receive input from head’s sensory systems
- motor control of facial and laryngeal muscles
6
Q
How do brain stem lesions affect the cranial nerves?
A
small lesions can entail selective dysfunction of specific nerves while sparing others → allows for clinical localization
7
Q
What characterizes the cranial nerves I?
A
- olfactory nerve
- ends in basal forebrain (above the brainstem)
8
Q
What characterizes the cranial nerves II?
A
- optic nerve
- only sends collaterals to the brain stem, specifically superior colliculi
9
Q
What characterizes the cranial nerves XI?
A
- accessory nerve
- ascends from spinal cord → fake cranial nerve
10
Q
What role does emotional processing play in the context of addiction?
A
- emotional processing can signal presence of or prospect for reward or punishment
- initiate motor programs to pursue or avoid
11
Q
What is the target of most drugs of abuse?
A
they act on elements of the limbic circuitry
12
Q
What are common drugs of abuse?
A
- Opioids
- Stimulants
- Alcohol
- Cannabinoids
- …
13
Q
How do Neurotransmitter play a role in the context of addiction?
A
- dopamine codes for reward prediction
- neurotransmitter release through drugs causes unphysiologically elevated levels with psychological alterations
14
Q
How does continued drug use affect the reward system?
A
- overstimulation due to unphysiologically elevated levels of neurotransmitters causes internalization of receptors
- leads to dampened response of emotional reinforcement circuitry to natural less potent rewards
- leads to habituation, dosage increase for similar effects, drug seeking behavior
15
Q
What are the two dopaminergic systems in the brain?
A
- substantia nigra pars compacta (SNc)
- ventral tegmental area (VTA)
16
Q
How are dopaminergic cells classified?
A
- classifying according to gene and protein expression
- variety of subtypes
- some do not strictly adhere to SNc-VTA separation
- some show mixed properties
- some extend to surrounding nuclei
17
Q
The VTA is the origin of which pathways?
A
- mesolimbic pathway
- mesocortical pathway
18
Q
What is the mesolimbic pathway?
A
- dopaminergic pathway
- from VTA to basal ganglia and amygdala
19
Q
What is the mesocortical pathway?
A
- dopaminergic pathway
- from VTA to PFC
20
Q
What is the main target site for the VTA?
A
the ventral striatum (=nucleus accumbens and ventral parts of putamen)
21
Q
What neurotransmitters do VTA neurons transmit?
A
- dopamine
- some co-transmit dopamine with glutamate or GABA respectively
22
Q
What functions are VTA neurons implicated in?
A
- incentive-based behavior
- cognition
- motivation
23
Q
Which VTA neurons target what area?
A
- VTA Neurons activated by motivation and reward densely innervate the nucleus accumbent core region
- aversion-encoding VTA neurons target the Nucleus Accumbens shell region
24
Q
The ventral SNc is the origin of which pathway?
A
the nigrostriatal pathway
25
What do vertrag SNc neurons target?
the dorsocaudal part of the striatum (= caudate nucleus and dorsal putamen)
26
What SNc neurons are differentiated in terms of their functions?
- ventral SNc neurons
- dorsal and lateral SNc neurons
27
What are ventral SNc neurons implicated in?
phasic ventral SNc neuronal firing is associated with
- start-stop signals
- acceleration in movement
28
What are dorsal and lateral SNc neurons implicated in?
- more similar to VTA neurons
- salience and novelty detection
- reward prediction
- contribute to mesolimbic pathway
29
How does ablation of a ALDH1A1 subtype affect rodents?
- deficit in acquiring new motor skills
- no effect on consolidated skills
30
What is different about ventral SNc cells in Parkinson's disease?
ventral SNc cells contain less neuromelanin pigment than dorsal cells and are selectively lost in PD
31
How does neuromelanin play a role in PD?
neuromelanin sequesters toxic dopamine metabolites (quinones) and bins iron
→ helps prevent intracellular aggregation of alpha-synuclein and mitochondrial dysfunction
32
What is thought to be the cause of premature cell death in PD?
the aggregation of alpha-synuclein (Lewis bodies) and mitochondrial dysfunction
33
How might genetic variants influence vulnerability to PD?
genetic variants may intensify the vulnerability of dopaminergic cells to PD
34
What distinguishes ventral SNc cells and VTA cells?
- ventral SNc cells are much larger
- ventral SNc cells have extremely branched axonal endings
- ventral SNc cells show high-intensity burst firing
35
What is a characteristic feature of the baseline activity of ventral SNc cells?
ventral SNc cells exhibit high baseline activity and have limited capacity to increase mitochondrial respiratory activity under stress
36
Why are ventral SNc cells more vulnerable than other dopaminergic cells in PD?
“multiple hits” make ventral SNc cells more vulnerable than other dopaminergic cells
37
What is sugar?
“sugar” commonly refers to sucrose
38
What is sucrose?
- a disaccharide
- consists of 1 glucose and 1 fructose molecule
39
How is sucrose absorbed?
- intramolecular bond is cleaved in gut
- glucose and fructose are absorbed via different metabolic pathways
40
What is unique about Glucose?
Glucose is the only nutrient the brain can use for energy production
41
What can be said about sugar and reward?
- high reward value of glucose well-known
- sugar conditioning possible even if no sweetness is tasted (e.g. direct intestinal infusion via gastric tube)
- cells necessary and sufficient for sugar conditioning are found in proximal small intestine (duodenum, jejunum)
42
What does sugar generally signal?
high caloric value
43
How do fructose and glucose compare in terms of their effects?
physiological responses are generally much stronger to glucose than to fructose
44
What are neuropod cells?
- a new cell type that was discovered
- neuron-like behavior
- in mucosal lining of the gut
45
What processes cause a depolarization of the neuropod cells?
- on binding of sodium-glucose co-transporter (SGLT1) channels influx of sodium
- Taste-receptor (T1R3) like receptors start second-messenger cascade with release pf Ca2+ from intracellular storages, which opens a second set of Na+ channels (TRPM5 channels)
- K ATP-channels close on intracellular binding of ATP-increase (after intracellular glucose metabolization)
- voltage-gated calcium channels (VGCC) amplify process and induce hormone release
46
How is glutamate relevant in neuropod cells?
- axon-like extensions harbor vesticles with glutamate
- glutamate is released onto dendrites of the vagal nerve
→ cause excitatory post-synaptic potentials
→ vagus nerve forwards signal to the nucleus tractus solitaires (NTS) in the medulla
47
Where does the NTS receive input from?
- oral cavity (sensation of sweetness and intestinal sugar signaling
- olfactory cues (motivational)
- visual cues (motivational)
48
Where does the NTS project to?
- hypothalamus
- central nucleus of amygdala
- locus coeruleus (release of noradrenaline increases arousal)
- dorsal raphe (serotonin increases motivation and mood)
- SNc
- VTA
49
How does sugar intake affect dopaminergic pathways?
sugar intake increases activity in mesolimbic and nigrostriatal pathways
50
What are sham-fed rats?
- taste of sweetness but no glucose ingestion
- mesolimbic increase but not nigrostriatal
51
How does the vagus nerve affect the dopaminergic pathways?
- left vagus nerve shown to increase mesolimbic activity
- right vagus nerve increases nigrostriatal activity
