Lecture 5 Flashcards
1
Q
Types of neurotransmitters
A
Amino-acids (smallest but largest concentration)
Amines (mid-size, mid-concentration)
Peptides (largest, lowest concentration)
2
Q
Transport of enzymes from the cell body to the presynaptic terminal
A
By the kinesin on the microtubulin
3
Q
Are amino-acids and amines short or long-duration neurotransmitters?
A
short
4
Q
How are amino-acids and amines mostly inactivated?
A
Largely through reuptake
5
Q
Where are amino-acids and amines synthetized?
A
Synaptic terminal
6
Q
Where are peptides synthesized?
A
In the cell-body
7
Q
How are peptides inactivated?
A
Through breakdown and diffusion
8
Q
Cytoskeleton
A
Scaffolding within a neuron, dendrites, axon etc.
9
Q
Tubulin
A
In proximal axon, dendrites and soma
10
Q
Tau (microtubulin binding protein)
A
In axon
11
Q
Parts of the cytoskeleton
A
Tubulin, neurofilament, microfilament
12
Q
Actin
A
In growth cone, heads of the dendritic spines
13
Q
Anterograde (Orthodrome)
A
From soma to synapse
14
Q
Retrograde (Antidrome)
A
From synapse to soma
15
Q
Retrograde tracers
A
Horseradish peroxidase (HRP), Fluoro gold (FG), Cholera toxin (CT), Fast Blue (FB)
16
Q
Anterograde tracers
A
Phaseolus vulgaris leucoagglutinin (PHA-L)
17
Q
Tracers
A
Hijack the transport system along the microtubui
18
Q
How does anterograde tracing work?
A
Inject tracer in an area, tracer is taken up by the cell-body, kinesin transports it
19
Q
Antibodies in tracing
A
Primary - binds to the protein of interest
Secondary (such as HRP) -binds to the primary antibody
20
Q
Layer 2-3 of cortex
A
Send information to other cortical areas (ipsi- and contra-laterally)
21
Q
Layer 5
A
Connect to subcortical structures (such as striatum and colliculus)
22
Q
Layer 6
A
Projects back to the thalamus
23
Q
Layer 4
A
Thalamus sends information to this layer
24
Q
Acetylcholine ion channels
A
Nicotinic receptor
25
Is acetylcholine part of the diffuse modulatory systems?
Yes
26
Production of acetylcholine depends on 2 enzymes
1. Achetylcholine esterase (ACHE)- recycles Ach
2. Choline acetyl transferase (CHAT) - makes Ach
27
How does ChAt build acetylcholine?
From Choline + Acetyl CoA
28
How does ACHE manage the reuptake
Breaks down ACH into Choline + acetate
29
Novichok
Organophosphate that blocks ACHE --> No reuptake of Choline --> No making of ACH
30
Where are ACH receptors most prominent?
In the muscles
31
Symptoms of novichok poisoning
First spasms because the first abundance of ACH over activates the muscles --> Then no more ACH production because choline reuptake is not possible, so neuromuscular paralysis
32
Where are vesicles?
In a reserve pool
33
What connects the individual vesicles to each other?
Synapsin
34
What breaks down the bonds made by the synapsin so that the vesicles become available?
CAMK-II (cam kinase II) - calmodulin dependent protein kinase type II
35
What primes and docks the vesicles in the membrane?
SNAPs and SNAREs
36
Core elements of the SNARE complex
Synaptobrevin (in the vesicle membrane)
SNAP-25, Syntaxin (in the presynaptic membrane)
37
Fusion of the vesicle with the presynaptic membrane?
SNARE complexes form vesicle docks; synaptotagmin binds to SNARE complexes; Ca2+ binds to synaptotagmin which leads to the curvature of plasma membrane so membranes come together --> fusion
38
Synaptotagmin
Is a Ca+ sensor, triggers the fusion of the membranes
39
Clathrin
Coats a piece of membrane that will become the retrieved vesicle
40
Dynamin
Pinches the vesicle (the recovered piece of the membrane from the membrane itself)
41
Actin
Kinesin transports the pinched off recovered vesicle via the Actin
42
Auxilin
Removes the clathrin coat --> retrieved vesicle
43
Where is most of the Acetylcholine made?
Medial septal nuclei and in the basal nucleus of Meynert (both in Basal forebrain, communicates with the cortex)
44
In which area is acetylcholine made that communicates with the thalamus?
Ponto-mesencephalo-tegmental complex
45
The 2 types of ACh receptors
Ion channels (nicotine - gated)
Metabotropic receptors (muscarine)
46
Nicotine ACh receptors (nAChr)
Has 5 subunits
Fast and short-acting
When Ach binds gate flips open
47
Ligand-gated receptors
ACh, GABA, AMPA, NMDA, Glycine, Kainate, serotonin, and purine receptors
48
Metabotropic receptor characteristics
Have no pore, do not let ions in, but have a G-protein coupled in the inside
--> Are slow and long-lasting
49
How do G-protein coupled (metabotropic) receptors work?
Neurotransmitter binds to the receptor --> G-protein in the inside gets activated --> Subunit of the G-protein or an intracellular messenger modulate ion channel --> Ion channel opens
50
Metabotropic receptors are ...
Muscarinic, glutamate, dopamine, GABAb, adrenergic, histamine, serotonin and purine receptors
51
What does ACh do in the brain?
Enhances long-term potentiation, learning, working memory, enhances selective attention, involved in the generation of neuronal oscillations
52
ACh's role outside the brain
Transmitter at the neuromuscular junction
Transmitter of the PNS: rest and digest function
53
Alzheimer's disease
Degeneration of ACh nuclei in the basal forebrain
54
Myasthenia Gravis
Antibodies against nACh in neuromuscular junction -autoimmune disease (peripheral problem) --> It "eats" your receptors -> Muscle strength decreases
55
Medicating Alzheimer's disease
-ACh esterase blockers: Rivastigmine, Galantamine - temporarily beneficial on attention, concentration and speech performance in patients with mild to moderate dementia (more ACh left)
-NMDA blockade: Memantine - prevents overexcitation of glutamate because of which cells could die
56
Side effects of Alzheimer's medication
Nausea, diarrhea and tiredness
57
MEPP
Muscular Endplate Potential - Amplitude of this gets lower in myasthenia gravis
58
- MG medication
-Cholinesterase inhibitors - pyridostigmine: enhance communication between nerve and muscles
-Corticosteroids -prednisone: inhibit immune system--> limiting antibody production. (side effects: bone-thinning, weight-gain, diabetes, infections etc)
-Immunosuppressants: side effects: nausea, vomiting, liverdamage, kidney damage, increased risk of infection
59
inhibitor of nACh receptor
Curare- venoms of some snakes
Reversible nACh receptor blockers for anaesthesia
60
Inhibitor of muscarinic ACh receptor blockers
atropine: ACh antagonist, leads to pupil dilation, resuscitation
61
Glutamate reuptake
By excitatory amino acid transporters via astrocytes
62
Glutamate is made out of
Glutamine by glutaminase
63
Packaging protein of Glutamate
VGLUT
64
Experiment with human astrocytes in the mouse brain showed that...
Astrocytes are involved in learning and memory
65
Glutamate ion channels
AMPA, NMDA, and Kainate receptors
66
How do the AMPA receptors work?
They have subunits that change when the neurotransmitter binds to the channel (like with nACh receptors). Short and fast effect
67
How do the NMDA receptors work?
They can open and close (so Ca2+ and Na+ can flow in), but they are blocked by Mg2+. First depolarization is carried by AMPA. --> NMDA channels have a longer effect in depolarization (Basically depolarization opens the NMDA channel)
68
What does Glutamate do?
Mediates fast excitatory transmission (dangerous to modulate it)
69
NMDA receptors are involved in ...
Short and long-term memory
70
What happens after the blockade of NMDA receptors?
hallucinations, other psychosis-like symptoms, and dissociative anaesthesia
71
Is excessive glutamate toxic?
Yes, can lead to ischemia and epilepsy
72
What do learning and memory depend on?
Long-term potentiation
73
LTP
-Is a long-lasting increase in EPSP amplitude
-AMPA and NMDA have to coexist. LTP happens when there is high-frequency transmission (glutamate binds to AMPA and NMDA receptors), strong depolarization, Ca2+ enters the cell
74
How can LTP be studied?
With the Morris water-maze
75
Standardized excitation goes up...
after LTP, and stays high for a longer time
76
In regard to LTP, if you block NMDA receptors ...
You have an initial activation, but it is not stored in the memory
77
What ion's influx is essential for LTP?
Ca2+
78
Dendritic spines ...
Can grow
Actin makes the spines bigger after LTP (and also makes more of them)
79
CaMK II's role in LTP
Triggers synaptotagmins to fuse more AMPA receptors in the membrane
80
If you block CaMK II
Impaired place learning
Studied with knockout mice
81
Late LTP
Depends on a protein in the cell-body called CREB
New spines
82
Early LTP
NMDA, AMPA activation; addition of postsynaptic AMPA receptors after LTP; synaptotagmin mediated
83
Long-term depression
Prolonged low-frequency stimulation
84
Neurogenesis
Growth of new neurons and connections from stem cells
85
Neurogenesis was found in ...
Hippocampus
Caudate nucleus
86
GABA receptors are ...
Inhibitory
87
GABA is made from
Glutamate by glutamic acid decarboxylase
88
Excess GABA from the synaptic cleft is taken up ...
Via the glial cells and GAT cotransporters
89
Gamma-hydroxybutyrate (GHB)
Rape drug: excess GABA (inhibition of breakdown) --> more inhibition --> sedative effect
90
Gaba receptor
Many, we have to know the ionotropic one
91
Ionotropic GABA receptor
Permeable for Cl- -->Inhibits the target cell
92
Agonists of GABA channels
Benzodiazepines, barbiturates
93
Antagonists of GABA channels
Convulsants: excite the target cell (picrotoxin, bicuculline)
94
Shunting inhibition
If you excite a neuron and have an EPSP but simultaneously activate the inhibitory synapse, it prevents the EPSP from leading to action potential
95
What does the GABA system do?
Local balance of excitation through GABAergic inhibition
Inhibition prevents overexcitation (epilepsy)
Pulsed inhibition generates neuronal oscillations (important for cognition)
Excessive GABAergic inhibition leads to sedation or narcosis
96
Young GABA receptors lead to
Cell depolarization (because after birth way more Cl- is inside than outside)
97
What connect the clathrin to the plasma membrane?
Adaptor proteins: AP-2, AP-180
98
What happens in ischemic stroke?
Oxygen deficit in brain: no ATP
No glutamate reuptake, continuous depolarization, excessive Ca2+ influx --> cell death
