Synapse structure and function Flashcards
1
Q
- What makes up a chemical synapse
A
Formed by the close association of an axon terminal of the presynaptic cell with some part of the post synaptic cell
2
Q
- What is the space between cells in a synapse called; how wide is this usually
A
Synaptic cleft; typically 20 nm across
3
Q
How are synapses classified?
A
By where on the receiving cell they are located.
4
Q
What are three types of chemical synapses
A
Axodendritic, axosomatic and axoaxonal
5
Q
Where are neurotransmitters stored in the axon terminal?
A
Spherical, clear, small synaptic vesicles (50 nm accross), in association with microtubules which transport them to the presynaptic membrane
6
Q
Where does neurotransmitter release occur?
A
The active zone. Presynaptic membrane has dense projections which are involved in the docking of the synaptic vesicles at the active zone
7
Q
The post synapse dendrite is thickened as what?
A
Post synaptic density
8
Q
What are usually the differences between axodendritic and axosomatic synapses?
A
Axodendritic synapses are asymetrical and have a well developed post synaptic density, they are usually excitatory. Axosomatic synapses are symmetrical, pre and post synaptic densities of comparable thickness. They are inhibitory.
9
Q
How many synapses does the cortex have?
A
As many as 10^13
10
Q
What are the features of synapses with extremely wide (100- 500 nm) synaptic clefts?
A
They often secrete a catecholamine and have large dense-core vesicles (LDCVs) 40- 120 nm across.
11
Q
Other than wide synaptic clefts, where are LDCVs found?
A
Peptide-secreting neurons
12
Q
Why do most synapses contain both small synaptic vesicles and LDCV?
A
Many neurons secrete more than one neurotransmitter
13
Q
What triggers neurotransmitter release?
A
Transmitter release requires a rise in intracellular Ca2+, by voltage-dependant calcium channels, triggered by the arrival of the action potential at the axon terminal
14
Q
How long does it take for the transmitter to cross the synaptic cleft?
A
5 us.
15
Q
what happens when the transmitter reaches the postsynaptic membrane
A
Binds to specific receptors, changes its conformation , changing the postsynaptic membrane permeability to specific ions
16
Q
What are the two types of Neurotransmitter superfamilies?
A
Ligand-gated ion channels (ionotropic receptors) and G-protein coupled receptors (metabotropic receptors)
17
Q
Activation of G proteins can lead to what processes?
A
G proteins are capable of of effects on membrane permeability, excitability, and metabolism. They can influence permeabilty either by binding ion channels directly or by modifying the activity of second messenger system enzymes which phosphorylate ion channels.
18
Q
What two possible effects can the production of post-synaptic potentials have?
A
-Excitatory response or inhibitory
19
Q
What are the features of classic neurotransmitter molecules?
A
Small molecules, amino acids or amines
20
Q
Which neurotransmitters and receptors are responsible for fast neurotransmission?
A
Glutamate, GABA, acetylcholine, via ligand gated ion channels.
21
Q
Which receptors and neurotransmitters are responsible for slow neurotransmission?
A
G protein Coupled receptors. the same transmitters can mediate slow and fast transmission by acting on different receptor types, but catecholamine and peptide transmission are invariably slow.
22
Q
What does cotransmission entail?
A
release of a classical (amino acid/ amine) transmitter, coupled with the co-release of one or more peptides at higher firing frequency
23
Q
How are transmitters cleared from the synaptic cleft?
A
Passive diffusion, reuptake into surrounding neurons or glia, or enzyme degradation.
24
Q
What is the structure of gap junctions/ electrical synapses?
A
Arrays of paired hexameric ion channels called connexons. the channel pores are 2-3 nm in diameter
25
How do gap junctions/ Electrical synapses allow for APs to spread between cells?
The channel pores allow small molecules to permeate between neighbouring neurons, therefore electrically coupling the neurons.
26
what are key features of electrical transmission?
Extremely rapid, signals transmitted with no distortion and works in both directions. Gap junctions between cells can close
27
How does the central core of a gap junction close?
Each connexon is made up of six subunits called connexins. They rotate to close the pore in response to an increase in intracellular Ca 2+ concentrations.
28
By what process does vesicular release of transmitter occur?
Exocytosis
29
By what process is the vesicle membrane recycled from the presynaptic membrane to form new vesicles?
Endocytosis
30
Neurotransmitter is released in discrete packets or....
Quanta
31
What does each quantum represent?
Release of the contents of a single vesicle, about 4000 molecules of transmitter.
32
In CNS synapses what does the release of quantum cause?
Miniature postsynaptic potential (mpsp), either excitatory or inhibitory
33
What do post synaptic potentials represent?
Summation of multiple MPSPs generated by an AP invading several active zones simultaneously (either axons will branch into multiple terminals or a terminal will have multiple active zones).
34
THe active zone of many CNS synapses appears to have one release site this is known as....
one vesicle or one quantam hypothesis
35
Individual active zones behave in an all-or-none fashion because...
an AP will either trigger the release of the single quantam or not
36
What is the calcium concentration gradient at the active zones?
Free calcium concentration at rest in a terminal is 100 nM while the external concentration is 1mM
37
What restricts the rise in calcium concentration to within 50 nm of the channel mouth?
Presence of diffusion barriers and calcium buffers in the terminal
38
the [Ca] within 10 nm of the channel mouth rises to between ________, which matches the half-maximal concentration of Ca for glutamate release
100 - 200 uM
39
What is the difference in the release from clear synaptic vesicles and large dense-core vesicles?
Release from LDCVs takes longer and has a higher affinity for calcium (half maximal release occurs at about 0.4 uM) because only a small amount of calcium manages to diffuse to the LDCVs
40
What are the features of exocytosis of amines and peptides by LDVVs?
Occurs with a delay of 50 ms and only in response to high frequency firing of the neuron which causes high levels of calcium influx.
41
what are the two pools of small clear synaptic vesicles
Releasable pool ( in the active zone and can take part in repeated cycles of exo and endocytosis at low firing frequencies) and Reserve pool (vesicles tethered to cytoskeletal proteins and can be recruited by repeated stimulation to join the releasable pool)
42
How do the vesicles become liberated from the cytoskeleton?
calcium dependant phosphorylation of synapsin I, a protein that anchors vesicles to actin filaments in the terminal
43
Which process aligns vesicles at specific sites in the active zone; what proteins does this involve?
Docking which involves SNARE proteins
44
During docking which SNARE proteins bind?
Vesicle- associated protein synaptobrevin (v-SNARE, VAMP) binds to presynaptic membrane protein syntaxin (t-SNARE).
45
What is syntaxin closely associated with?
Voltage-gated calcium channels
46
Synaptobrevin, syntaxin and which other protein is crucial for docking?
SNAP-25
47
What are the targets for botulinum toxin to inhibit neurotransmitter secretion?
Synaptobrevin, syntaxin and SNAP-25
48
After docking, comes another calcium dependant step called...
Priming
49
What is the process of priming?
A number of soluble cytoplasmic proteins form a transient complex with the SNAREs, resulting in partial fusion of vesicle and presynaptic membrane. This involves the hydrolysis of ATP
50
After a vesicle is primed what is required for exocytosis?
A large pulse of calcium to permit complete fusion of the presynaptic membranes and opening of the fusion pore through which exocytosis occurs.
51
What is synaptotagmin?
The calcium sensor in the exocytotic machinary. In the absence of calcium it prevents complete fusion, when it binds calcium it undergoes a conformational change which allows fusion to proceed.
52
Following exocytosis, synaptic vesicles are recycled within 30- 60 s by endocytosis. What is the first step?
Vesicle membrane acquires a clathrin coat, distorting it so that it invaginates into the terminal
53
In the heuser-reese cycle endocytosis, what is the step after the clathrin coat forms?
GTP-binding protein dynamin forms a collar around the neck of the invagination. Hydrolysis of bound GTP triggers the fission of the coated vesicle from the presynaptic membrane.
54
GTP-bound dynamin requires what to facilitate endocytosis?
Calcium
55
What is the faster kiss-and-run cycle that operated at central synapses?
Vesicle fuses with presynaptic membrane to open a pore through which transmitter discharges, after which the pore closes and the vesicle disengages. No endocytosis
56
What is the benefit of the kiss-and-run cycle being only 1 s
it is able to support extended periods of high release with only 35-40 vesicles in the recycling pool
57
What is the process of vesicles refilling?
Receptors are acidified by the action of proton ATPase. Transport of transmitter into the vesicles is driven by secondary active transport with H+ efflux providing the energy
58
Where are peptide transmitters synthesised
In the cell body. They are then secreted in the lumen of the rough endoplasmic reticulum and packaged for export by the golgi apparatus , from which loaded vesicles are budded. These are moved to the terminal by fast axoplasmic transport
59
What are autoreceptors?
Presynaptic receptors for the transmitter released by the neuron in which they are located.
60
What are the functions of autoreceptors?
They are metabotropic, they have homeostatic functions. Decrease the release of neurotransmitter by reducing calcium influx into terminal. Some can decrease the synthesis of the transmitter. Some dopaminergic neurons have dopamine receptors on their dendrites and cell bodies to regulate neuron firing rate.
61
What are the benefits of the negative feedback mechanism of autoreceptors?
Avoid excess excitation or to curtail postsynaptic receptor desensitization, which would reduce the sensitivity of the synapse
62
What are heteroceptors?
Presynaptic receptors for transmitters not secreted by the neuron on which they are located
63
What are the functions of heteroceptors and what is the most common example?
They regulate transmitter release. GABA receptors at glutamatergic synapses reduce glutamate release. They are activated by GABA that has diffused from neighbouring synapses.
64
What are the functions of voltage-dependant calcium channels ?
Control the influx of calcium which couples excitation to transmitter release, calcium action potentials in dendrites, excitation-contraction coupling in muscles.
65
How can calcium channels be differentiated?
Electrophysical properties, sensitivity to blockade by drugs and toxins, their distribution and functions.
66
Which are the high-voltage activated channels?
N-, P-, Q- type
67
What are depolarizing postsynaptic potentials termed?
Excitatory post synaptic potentials
68
when do epsps have a prospect of driving a neuron across the threshold?
when many epsps are generated on a neuron within tens of milliseconds of each other.
69
What are the major fast excitatory transmitters?
Glutamate and acetylcholine
70
Generally what is the size of epsp?
they are small and graded in size ranging from fractons of a millivolt to about 8 mV. Stimulating more axons activates more synapses, which makes the epsp larger.
71
what is synaptic delay?
there is a short delay of 0.5 - 1ms betweem stimulating the afferents and the generation of an epsp
72
How long do epsps generally last?
they typically last for 10-20 ms whilst decaying exponentially.
73
Activation of which ionotropic receptors reduces the probability of neuron firing?
Ionotropic receptors that conduct chloride ion channels.
74
Which are the most important fast inhibitory transmitters?
GABA and Glycine
75
At what membrane potential does GABA produce no change in potential and why?
-70 mV. This is the equilibrium potential for chloride. At this point there is no net flow of cl- through the activated GABA receptor.
76
What is an inhibitory posynaptic potential?
A modest hyperpolarization, carries the membrane potential away from the threshold for firing action potentials.
77
In all cases, no matter the cell membrane potential, what is the effect of increasing cl- permeability?
Force the membrane potential towards the Ecl- (-70mV), whenever the potential is not the same as Ecl-, there will be an ionic driving force causing chloride ions to either leave or enter the cell. This prevents it from being driven towards threshold by concurrent excitatory inputs.
78
What is the inhibition of GABA activated chloride receptors called?
shunting inhibition
79
Why are metabotropic receptors' effects slower in onset and longer lasting than the ionotropic receptor action?
they couple to second messenger systems. They affect ion channels only indirectly via a cascade of events which take time to switch on and off.
80
What is unique about the second messenger systems of metabotropic receptors?
They are freely diffusible. They can spread through dendrites into the cell body or even the axon. this brings them into contact with channels throughout a nerve cell.
81
What are some of the ion channels targeted by second messenger systems?
voltage dependant K channels responsible for setting the overall excitability of the cell, voltage-dependant channels that generate action potentials. Ca2+ channels required for transmitter release, and ligand-gated ion channels (altering the efficacy of fast transmitters)
82
Why do metabotropic receptors exert long-lasting effects on nerve cells?
Second messenger systems act in the nucleus to alter gene transcription. this ca alter the structure of neurons and how they connect to their neighbours.
83
Why does transmitter inactivation occur?
Allows synapses to respond to rapid changes in presynaptic neuron firing, limits receptor desensitization.
84
What are the three ways transmitters are inactivated?
Enzyme-catalyzed degradation, transport out of the cleft back into neurons or glia, or by passive diffusion
85
How is acetylcholine hydrolyzed?
It is hydrolyzed by acetylcholinesterase which cleaves the transmitter molecule into choline and acetate. Choline is taken back into the presynaptic nerve terminal by a Na- dependant transporter
86
Other than acetylcholine, what other transmitter is inactivated at the synapse by enzyme-catalyzed degradation
Adenosine 5'- triphosphate (ATP)
87
What is the difference between amino acid transmitter and amine transport?
Amino acids may be transported into both neurons or glia, whereas amines are transported into only neurons.
88
What are the two families of transporters of neurotransmitters?
Na/K co transporter family (glutamate and aspartate transporters)
Na/Cl cotransporter (Transporters for GABA, glycine, NA/adrenaline, dopamine, serotonin, and choline)
89
Glutamate transport is electrogenic, what does this mean?
It results in a modest potential difference being set up across the membrane, inside positive. A consequence of this is that the excessive depolariation of the membrane can reverse the direction of the transport -> excitotoxicity
90
What is the mechanism of action of cocaine?
Its target is the dopamine transporter. In inhibits dopamine reuptake, it deranges dopamine transmission in reward pathways in the brain.
91
What is the structure of the transporters in the Na/cl family?
They are large glycoproteins with 12 transmembrane segments, but have no homology with vesicle transporters.
92
Other than transporters, what is an important method of inactivation of GABA and glutamate?
Diffusion out of the synapse.
93
What is the major route for terminating the synaptic action of peptides?
Diffusion
94
Other than diffusion, what is the other mechanism for peptide inactivation?
They are internalised by neurons via receptor-medicated endocytosis and then degraded by non-specific peptidases.
95
Why are peptide actions prolonged?
Peptides are larger than classical transmitters, there are significant barriers to free diffusion out of the cleft, they clear slowly from a synapse.
96
What is the decay of small potentials determined by?
Physics of the neuron. The smaller the diameter of the neuron, axon or dendrite, the shorter the distance over which it will decay, the faster this will happen and the slower the potential is conducted.
97
Why is the decay of individual potentials relevant?
it is crucial in determining how neurons integrate their inputs and how information is processed in the nervous system, it accounts for why APs (which do not decay), are needed for long-distance transmission.
98
Why can't synaptic potentials carry information a great distance?
They decay to zero within a few millimeters in most neurites
99
what is a special property of ipsps and epsps?
They are able to summate
100
Why the axon hillock crucial for neuron firing?
It has the highest density of voltage dependant sodium channels and therefore the lowest threshold
101
The decision to fire or not is made by which region of the neuron and on what basis?
The axon hillock, on the basis of whether the sum total of the epsps and the ipsps cause its membrane potential to become more positive than the firing threshold.
102
In pyramidal cells, how many excitatory synapses must be activated, on average, to trigger an action potential?
100
103
What does the efficacy with which a synapse can influence firing depend on; and why ?
its position, because post synaptic potentials decay as they spread passively towards the hillock.
104
What is the relative strength of a synapse in contributing to a neuron's output called?
it's weighting. This is not a fixed property but may change over time
105
What is temporal summation?
When an afferent neuron fires a series of APs in quick succession, the earliest psps generated in the post synaptic cell will not have time to decay before the next psps arrive, hence the successive psps summate over time. If sufficient, it will cause the cell to reach the firing threshold.
106
What is spatial summation?
The summing of psps generated at separate points on the neuron surface.
107
Temporal and spatial summation are distinct processes but do they occur at the same time on a neuron?
Yes, their combine effect dictates whether a neuron will fire
108
the frequency with which a cell fires and how long it fires, is determined by what?
Amplitude and duration of the axon hillock membrane
