Workshops Flashcards
1
Q
What are the four steps in the exocytosis of NTs?
A
Trafficking.
Docking.
Fusion.
Exocytosis.
2
Q
Which molecule helps traffic vesicles to the active zone?
A
Actin.
3
Q
Which complex is involved in docking vesicles to the membrane?
A
Complex of SNARE proteins.
4
Q
Fusion between the vesicle and the membrane requires an increase of which ion in the cytosol?
A
Calcium.
5
Q
What is synaptotagmin?
A
A calcium sensor.
6
Q
Which molecule binds to synaptotagmin?
A
Calcium.
7
Q
What is the action of synaptotagmin?
A
Stimulates the v- and t-SNAREs to combine into an alpha-helical-shaped complex.
8
Q
What is the action of the SNARE complex?
A
Forces the two membranes together (fusion) and then pulls them apart to spill the vesicle contents into the synaptic cleft (exocytosis).
9
Q
Which three main structures are involved in declarative memory?
A
Sensory neocortex.
Parahippocampal cortices.
Hippocampal formation.
10
Q
Which four regions make up the sensory neocortex?
A
Parietal lobe.
Temporal lobe.
Prefrontal cortex.
Neocortex.
11
Q
Which three regions make up the parahippocampal cortices?
A
Parahippocampal gyrus.
Perirhinal cortex.
Entorhinal cortex.
12
Q
Which four regions make up the hippocampal formation?
A
Dentate granule cells.
CA3.
CA1.
Subiculum.
13
Q
What is the main role of the entorhinal cortex in declarative memory?
A
Controls the flow of sensory information entering the hippocampus.
14
Q
Which elements make up the trisynaptic pathway?
A
Entorhinal cortex –> dentate gyrus –>
CA3 –> CA1.
15
Q
The expression of which receptor is extremely high in the CA2?
A
Adenosine A1 receptor.
16
Q
Which substance is an adenosine receptor antagonist?
A
Caffeine.
17
Q
What are the cognitive enhancing effects of caffeine?
A
Increase attention.
Enhances focus and mental acuity.
Improves memory.
18
Q
What is the believed role of adenosine A1 receptors in the CA2?
A
Mediate the cognitive enhancing effects of caffeine.
19
Q
Caffeine enhances synaptic transmission in which hippocampal area?
A
CA2.
20
Q
How does tetanus neurotoxin (TeNT) affect vesicle fusion and exocytosis?
A
Interferes with SNARE proteins that mediate vesicle fusion.
Prevents fusion of synaptic vesicles with presynaptic membrane.
Inhibits exocytosis.
21
Q
What is the effect of silencing area CA2?
A
Impairs social recognition memory without affecting other hippocampus-dependent behaviours.
22
Q
What is excitotoxicity?
A
Too much glutamate receptor activity causes neuronal damage and death.
23
Q
What is the mechanism behind excitotoxicity?
A
Depolarisation causes sodium and calcium entry into AMPA and NMDA receptors.
Persistent stimulation causes too much calcium to build up inside the neuron.
24
Q
What are the detrimental effects of sustained calcium overload?
A
Increased energy demand on neurons.
Mitochondrial dysfunction.
Energetic stress.
25
Which enzymes are affected by sustained calcium overload?
Proteases = cytoskeleton breakdown.
Endonucleases = DNA breakdown.
Phospholipases = release of arachidonic acid.
'Suicide' gene = apoptosis.
26
What are the three subfamilies of PKC isoforms, and how are they divided?
Conventional.
Novel.
Atypical.
Based on the cofactor(s) that activate them.
27
What is the structure of most PKC isoforms?
Regulatory N-terminal domain.
Hinge region.
Catalytic C-terminal domain.
28
Protein kinase M zeta (PKMZ) is an isoform of what?
PKCZ.
29
What is the structure of PKMZ?
Consists of catalytic domain only.
30
What is the role of PKMZ in LTP induction?
PKMZ is phosphorylated by PDK1 to achieve maximum activation.
31
What is the role of PKMZ in LTP maintenance?
PKMZ inhibits GluA2 AMPA receptor endocytosis.
32
How does zeta inhibitory peptide (ZIP) affect LTP?
Reverses established LTP by inhibiting PKMZ.
33
What is a channelrhodopsin (ChR)?
A light-sensitive ion channel.
34
What is the effect of light on ChRs?
Light absorption triggers a conformational change of the protein and gating of the channel.
35
What is a halorhodopsin?
A light-gated ion channel that is permeable to chloride.
36
What is the role of halorhodopsins?
Used to silence cells.
37
What is tetracycline-controlled transcriptional activation?
A method of inducible gene expression where transcription is reversibly turned on or off in the present of the antibiotic tetracycline or one of its derivatives.
38
What is contextual fear conditioning?
A rodent is placed in a novel environment.
Aversive stimulus is provided.
Rodent is removed from environment.
When it is returned to environment, rodent demonstrates a freezing response if it remembers and associates the environment with the aversive stimulus.
39
What two types of actions does ACh have in the body?
Muscarinic.
Nicotinic.
40
What are the muscarinic actions of ACh on the heart?
Decreases heart rate and cardiac output.
41
What are the muscarinic actions of ACh on blood vessels?
Vasodilation.
Decreases blood pressure.
42
What are the muscarinic actions of ACh in the respiratory system?
Bronchoconstriction.
Increased bronchial secretions.
43
What are the muscarinic actions of ACh in the CNS?
Excitatory effect.
Involved in learning, short-term memory and arousal.
44
What are the nicotinic actions of ACh at the NMJ?
Contraction of skeletal muscles.
Stimulates sympathetic and parasympathetic ganglia.
Stimulates release of adrenaline.
45
What are the nicotinic actions of ACh in the CNS?
Stimulates release of ADH (antidiuretic hormone) at the hypothalamus.
46
What are parasympathomimetic drugs?
A class of medications that activate the parasympathetic nervous system (PNS) by mimicking or modifying the effects of ACh.
47
Which type of cholinergic agent is methacholine?
Directly acting cholinergic agonist.
48
Which type of cholinergic agent is physostigmine?
Indirectly acting anticholinesterase.
49
What are the muscarinic actions of ACh in the GI tract?
Increases salivary and intestinal secretion.
Increases peristalsis.
50
What are the muscarinic actions of ACh on the eyes?
Causes miosis (constriction of pupils).
Increase drainage of aqueous humour.
51
What are the muscarinic actions of ACh on the bladder?
Increases contraction, leading to urination.
52
What can methacholine be used to treat?
Terminate attacks of supraventricular tachycardia.
53
How does physostigmine affect ACh levels?
Increases the concentration of ACh at sites of cholinergic transmission.
54
Why is physostigmine used to treat glaucoma?
It is used a miotic to constrict the pupil to allow drainage of aqueous humour.
55
Why is physostigmine used to treat anticholinergic poisoning?
It can penetrate the BBB.
It enhances the transmission of ACh signals in the brain.
56
Name six symptoms of anticholinergic poisoning.
Tachycardia.
Blurred vision.
Urinary retention.
Agitated delirium.
CNS depression/coma.
Seizures.
57
What is tabun?
A cholinesterase inhibitor/nerve agent.
58
Name six symptoms of tabun exposure.
Bradycardia.
Miosis.
Loss of bladder control.
Restlessness.
Lung blisters.
Convulsions.
59
In one sentence, summarise how rewards reinforce specific behaviours.
When an animal stumbles unexpectedly upon something it wants, the likelihood of reproducing the behaviour that helped attain it increases.
60
What physiological feature is though to underlie brain stimulation reward.
Projections from the VTA to the nucleus accumbens.
61
How does self-stimulation mimic drug abuse?
Starving rats provided with brief daily access to food will forego eating to press a level for brain stimulation. They are pursuing an artificial goal to the detriment of a biological need.
62
Define brain stimulation reward.
Animals will work hard and often to the detriment of their health or safety, e.g. crossing electrified grids, to receive electrical brain stimulation.
63
Which neurons are involved in the rewarding effects of both brain stimulation and drug use?
Midbrain dopaminergic neurons.
64
How do we know that drugs of abuse hijack the reward system?
Animals will work even harder to self-stimulate when given a drug of abuse.
65
Name the three categories that drugs fall into.
Activate GPCRs.
Bind to ionotropic receptors or ion channels.
Bind to biogenic amine transporters.
66
The dependence-potential of a drug is related to what?
Its potency in releasing dopamine.
67
How does a reward affect extracellular dopamine levels in the nucleus accumbens?
Increases extracellular dopamine levels.
68
All addictive drugs activate which system/pathway?
Mesocorticolimbic dopamine system.
69
What happens when the dopamine neurons of the VTA fire in bursts?
Large quantities of dopamine are released in the nucleus accumbens and prefrontal cortex.
70
Nicotine is the main psychoactive ingredient of tobacco. What is its effects?
It is responsible for the stimulant effects, reinforcement, dependence and addiction that result from tobacco use.
71
Which branch of the nervous system does nicotine activate?
Sympathetic nervous system.
72
Name the two main nicotine-induced cardiovascular effects.
Increased heart rate.
Increased blood pressure.
73
What happens when the body absorbs nicotine into the blood?
The adrenal glands are stimulated, causing adrenaline to be released.
74
Name five central effects of cannabinoids.
Impairment of short-term memory.
Subjective feelings of confidence and heightened creativity.
Catalepsy.
Hypothermia.
Increased appetite.
75
Name four central effects of cannabinoids.
Tachycardia.
Vasodilation.
Reduction of intraocular pressure.
Bronchodilation.
76
Where are cannabinoid receptors located in the brain and body?
CB1 = in the brain.
CB2 = in peripheral tissues.
77
Where in the brain are CB1 receptors concentrated?
Hippocampus.
Cerebellum.
Hypothalamus.
Basal ganglia.
78
Since CB1 receptors are concentrated in certain brain areas, how could you describe their distribution?
Not homogeneously distributed.
79
Describe how CB1 receptors signal via Gi/o.
Linked via Gi/o to inhibition of adenylyl cyclase.
Directly inhibit voltage-gated calcium channels.
Regulate G-protein-sensitive inwardly-rectifying potassium (GIRK) channels.
Influence gene expression, both directly by activating mitogen-activated protein kinase, and indirectly by reducing the activity of protein kinase A.
80
Is ethanol a CNS depressant or a CNS stimulant?
Depressant.
81
What are the central effects of ethanol in the nucleus accumbens?
Elevates dopamine levels and leads to increased reward drive (continue drinking).
82
What are the central effects of ethanol in the hypothalamus?
Increased feelings of thirst and hunger.
83
What are the central effects of ethanol in the cerebral cortex?
Poor judgement.
Reduces inhibition and increases confidence.
Increases pain threshold.
84
What are the central effects of ethanol in the cerebellum?
Decreases balance and coordination.
Slows reflexes.
85
What are the central effects of ethanol in the medulla?
Affects heart rate, temperature and breathing.
86
Which receptor does ethanol act upon to enhance inhibition in the brain?
GABAa receptors.
87
Describe how blackouts from high consumption of alcohol are believed to be caused.
Ethanol inhibits NMDARs in the hippocampus.
88
Opiates are what type of agent?
Analgesic agent.
89
Name the three families of endogenous opioid peptides.
Endorphins.
Enkephalins.
Dynorphins.
90
Name the three families of opioid receptors.
Mu.
Delta.
Kappa.
91
Describe how opioid receptors signal via Gi/o.
Inhibit adenylyl cyclase.
Activate inwardly-rectifying potassium channels (GIRKs).
Inhibit voltage-gated calcium ion channels.
92
What are the effects of opiates in the dorsal horn?
Inhibit transmission of nociceptive signals through the dorsal horn.
Act presynaptically to inhibit NT release from primary afferent terminals in the dorsal horn.
Act postsynaptically to reduce the excitability of dorsal horn neurons.
93
What is naloxone?
Opioid antagonist that rapidly reverses the effects of opioid drugs, and is used to treat opioid overdose.
94
Define psychomotor stimulants.
Large class of diverse compounds that stimulate arousal and motor activity.
95
What is the mechanism of action for psychomotor stimulants?
Blocks re-uptake of dopamine, and to a lesser extent noradrenaline and serotonin.
96
What type of drug is ephedrine?
Sympathomimetic drug.
97
How does ephedrine indirectly stimulate the adrenergic receptor system?
Increases the activity of noradrenaline at the postsynaptic alpha and beta adrenergic receptors.
98
Name the four main effects of ephedrine.
Increased heart rate.
Increased breathing.
Heightened senses.
Increased alertness and attention.
99
What type of drug is amphetamine?
Synthetic sympathomimetic drug.
100
Describe the mechanism of action for amphetamine.
Pumped into nerve terminals via the actions of the dopamine transporter (DAT).
Disrupts vesicular storage of monoamine transmitters.
Transmitters are pumped back out of the nerve terminal by the reverse action of the transporters.
101
What is amphetamine psychosis?
Repeated use of amphetamine can cause delirium, panic, hallucinations, and feelings of persecution.
102
Describe the mechanism of action for cocaine.
Potentiates the actions of monoamines at the synapse by inhibiting the actions of the dopamine transporter (DAT).
