Chapter 8 Synaptic Transmission Study Question/Overview of Lecture.
How does a excitory axoaxonic synapse work?
!) The 1st neuron releases a NT onto the 2nd neuron axon terminal 2) This stimulates a greater release of NT from the 2nd axon terminal onto the 3rd neuron
What will effect the opening and closing of the connexon channels?
1) Change in Vm 2)pH change 3)Ca+2 ion Concentration
How does a G protien direct coupling work?
1) Neurotransmitter binds to receptor 2)Activates G protein 3) Alpha Subunit is released, there is an exchange of GDP to GTP. 4) Alpha Protein goes to it's target and binds to the it's ion channel (opens or closes it)
How does a 2nd messenger excitatory synapse work?
1) Neurotransmitter binds to the receptor 2)Activates G protein 3) Activates Enzyme (Using ATP) 4) Produces second messenger (cAMP) 5) 2nd Messenger Activates Protein Kiase A 6) Phosphorylates protein 7) Ion Channel Opens or closes
NT is removed from the synaptic cleft by 3 ways, which are
1)Enzymatic degradation 2)Presynaptic reuptake protein reclaims NT 3)NT just diffuses away from the synaptic cleft, where the Astrocytes pick up the excess NTs
Neurotransmitters bind to 3 types of postsynaptic receptors:
1)Fast response ligand-gated ion channels 2)Enzyme-linked receptor 3)G protein coupled receptors
How is depolarization registered in fast excitatory synapse?
1)Lots of Na+ moves in and some K+ moves out 2)The meter registers a (+) millivolt increase 3)Creates an Excitatory Postsynaptic Potential If the EPSP is strong enough you get an AP
Hows does an inhibitory axoaxonic synapse work?
1)NT from the 1st neuron decreases NT release from the 2nd onto the 3rd neuron
Communication across a synapse
1. An AP arrives at the axon terminal of presynaptic cell And depolarizes the axon terminal due to voltage gated Na+ influx 2. Depolarization opens voltage gated Ca+2 channels 3. Influx of Ca+2 activates calmodulin (protein) 4. Ca-calmodulin activates Ca-calmodulin kinase II 5. Activated CMKII activates adenylate cyclase 6. Adenylate cyclase makes cAMP to activate protein kinase A (PKA) 7. PKA phosphorylates the tethring protein Rab holding NT vesicles sitting on the axon terminal membrane 8. PKA triggers the release of NTs 9. When a Rab protein is phosphorylated, it releases its vesicle containing NT 10. Released vesicles fuse with the axon terminal and NTs are exocytosed into the synaptic cleft 11. Exocytosed NT vesicle membrane material is recycled back into the cytoplasm to avoid axon terminal membrane buildup 12. Exocytosed NTs get restocked from reserved NT vesicles 14. CMKII also phosphorylates the proteins synapsin I and II that tether the reserve NT vesicles 15. Reserve NT vesicles are released from cytoskeleton and move down to restock the axon terminal membrane 16.Axon terminal is now ready for the next AP to arrive
$$$ Describe what happens after an AP arrives at an axon terminal and up to when a neurotransmitter is exocytosed.
1. An AP arrives at the axon terminal of the presynaptic cell and depolarizes the axon terminal due to the voltage-gated Na+ influx 2. Depolarization opens voltage-gated Ca+2 channels 3. The influx of Ca+2 activates Ca-calmodulin 4. calmodulin (CMKII) activates adenylate cyclase to make cAMP to activate protein kinase A 5. Protein KinaseA phosphorylates the protein (Rab)that is holding vesicles with NT on the axon terminal 6. Vesicles exocytose and NT is released into the synaptic cleft
$$$ What are the 3 ways neurotransmitters are removed from the synaptic cleft?
1. Enzymatic degradation (in the postsynaptic neuron) 2. presynaptic reuptake protein reclaims NT (recycling) 3. NT diffuses away from the synaptic cleft
Neurons of the CNS average between ______ & ___________
1000 and 10,000 synapses
$$$Synapses exist at 3 different sites, axodendritic, axosomatic and axoaxonic. What is the relationship between synapse location and the ability for a graded potential to trigger an action potential? Explain.
A graded potential triggered closest to the axon hillock has the greatest chance to trigger an axon potential because ions have LESS DISTANCE to travel and less surface area to diffuse out of the cell.
Peptide NTs that are stored farther away are released by a higher AP frequency
A higher AP frequency causes multiple rounds of Ca+2 influx that can't be removed fast enough Ca+2 from the previous AP is still present when the next AP arrives and reopens voltage-gated Ca+2 channels Ca+2 conc. inside the axon terminal is now higher so more calmodulin can be activated to activate adenylate cyclase to activate PKA to phosphorylate the tethering protein and release more NT
A graded potential triggered closest to the axon hillock can have the greatest effect. Why is this the case?
A shorter distance to axon hillock reduces the diffusion effect on the concentration of ion influx. When released close to the hillock, more ions reach the voltage-gated channels at the axon hillock
What is a Synapse?
A synapse is the site where a neuron communicates with its target cell
****?Presynaptic modulation of excitatory AP (Slide 44)
An AP arriving at axon terminal "C" or "D" alone releases an amount of NT that generates a graded postsynaptic potential in neuron "X" But doesn't trigger an AP in neuron "X" NT binds to receptors on the "C" axon terminal and activates a 2nd messenger 2nd messenger triggers greater Ca+2 influx at the presynaptic axon terminal "C" (mechanism unknown) Greater Ca+2 influx releases more NT from "C" onto postsynaptic neuron "X" and you get an AP
What cellular structure do electrical synapses use?
At electrical synapses, the plasma membranes of adjacent cells are linked together by gap junctions such that when an electrical signal is generated in one cell, it is directly transferred to the adjacent cell by means of ions flowing through the gap junctions.
$$$ Explain what the following sentence means: Binding of excitatory neurotransmitters to their postsynaptic receptors triggers a graded excitatory postsynaptic potential.
Depending on the influx of excitatory neurotransmitter, it may or may not trigger an AP. Excitatory Neurotransmitter will depolarize the cell membrane. Postsynaptic is the one that wants to be depolarized Graded Excitatory because it is a variable, it depends on the amount of neurotransmitter
Metabotropic receptors (G-protein coupled receptors)
Direct coupling of a slow response receptor to an ion channel
What are the two types of G protein Linked receptors?
Direct coupling slow response system 2nd Messenger Slow response system
What is divergent and convergent neural integration?
Divergence: a single neuron communicates with several other neurons Convergence: a neuron receives signals from other neurons
Convergence:
a neuron receives signals from other neurons
Divergence:
a single neuron communicates with several other neurons
How is the excitatory Neurotransmitter Acetylcholine removed?
Choline is reclaimed by reuptake proteins in the presynaptic side - Acetate diffuses out of the synapse
Ligand-gated Cl- channels(pump it in) work against ________________in postsynaptic cell
Cl ATPases (Pump it out) [Cl- ]
$$$ *?With a neuron, what happens when ___ up in postsynaptic membrane? a) a ligand-gated Na+ channel opens b) a ligand-gated K+ channel opens c) a ligand-gated K+ channel closes d) a ligand-gated Cl- channel opens e) a voltage-gated Na+ channel opens f) a voltage-gated K+ channel opens g) a voltage-gated Ca+2 channel opens Know the Graph, how the graph changes with the opening and closing of the ion channels! (SLIDE 37)
a) Na+ goes in, and the cell will depolarize b) K+ flows out of the cell, the cell will re-polarize (loose cations, becomes more - inside). It will become hyper polarized. c) K+ ability to leave is closed, K+ ATPase pumps are still pumping it in, so The cell will depolarize d) Cl- come in, the cell will hyper polarize (membrane becomes more negative) A-D are the ones which effect graded Potential. e) Na+ going out, The cell will depolarize f) The cell will repolarize g) The Ca+2 rushes in, The cell will depolarize
Acetylcholinesterase breaks acetylcholine down to ___ &___________
acetate and choline
____________ can be either excitatory and inhibitory
axoaxonic synapses,
The types of Chemical synapses
axodendritic, axosomatic, axoaxonic
Axodendritic Chemical synapse:
axon terminal of one neuron contacts a dendrite on a 2nd neuron
Axoaxonic Chemical synapse:
axon terminal of one neuron contacts the axon terminal of a 2nd neuron that is synapsing with a 3rd neuron
Axosomatic Chemical synapse:
axon terminal of one neuron contacts the cell body on a 2nd neuron
Why is there a time delay in synapses?
because it takes some time for enough Ca+2 to enter to trigger NT release from the presynaptic neuron axon terminal
The Neurotransmitter acetylcholine is made by transferring an acetyl group to choline by the enzyme _______
choline acetyltransferase
Gap junctions composed of different ________ protein subunits form a plaque
connexin
Chemical synapses are defined by where they _________ the postsynaptic neuron
contact
Inhibitory synapses ________ motor signals to avoid jerky motions
dampen
Adjacent cells use _________ synapses for communication
electrical
Two types of synapses:
electrical and chemical
Presynaptic modulation: the special case with axoaxonic synapses can
facilitate or inhibit depending on the type of axoaxonic synapse
In Parkinson's disease, ____________ interneurons aren't working to contribute to correct motion
inhibitory
Fast ligand-gated ion channels are referred to as _________
ionotropic receptors
Excitory Neurotransmitters is stronger when
more neurotransmitters are released by presymnaptic axon terminal, there will be more NTS hitting the post symnaptic receptors, and more ion channels open.
spatial
multiple neurons firing at same time
Neural integration:
neurons receive/send signals from and to multiple cells
$$$Chemical synapses always transmit in _____ direction. Because voltage gated sodium have no effect on the ligand gated channel, so it can only effect the downstream voltage gated channel.
one
Inhibitory signals can ________ an excitatory signal
override
NTs released from the axon terminal bind to receptors on the ________________
postsynaptic membrane
Axoaxonic synapses can alter the affect of a _______________ on the presynaptic axon terminal
presynaptic AP
Excitatory and inhibitory synapses are found on the ____________ cell
same
$$$ ***? Graded potential
shift in electrical charge in a tiny area of the neuron (temporary); transmits a long cell membranes leaving neuron and polarized state; needs higher than normal threshold of excitation to fire. It all depends on the amount that is released and how many ion channels you open up. A local voltage change in a neuron membrane induced by stimulation of a neuron, with strength proportional to the strength of the stimulus and lasting about a millisecond.
EPSPs and IPSPs can be received ______________ and the strongest one wins
simultaneously
Excitatory and inhibitory neurotransmitters can hit the target cell __________. This will cause both influx and efflux of ions
simultaneously
Electrical synapses are used where ________ is important. This is used in the retina to respond to light and dark adaptations and in heart muscle
speed
Depending on location, an axosomatic graded potential can create a _________signal than an axodendritic
stronger
Chemical messengers are passed to the ______ cell rather than electrical signals
target
Graded potentials do not have refractory period becuase
there is only 1 gate. They can be summed.
Why are inhibitory synapses so important?
they help us focus
There's a ___________ at chemical synapses
time delay
How is Conenxon used in beta cells of the pancreas?
Insulin secretion from pancreatic b cells is synchronized by signaling between cells Gap junctions allow Ca+2 to flow between b cells. This ensures adequate level of Ca+2 in each cell to trigger Cacalmodulin-mediated release of insulin-containing vesicles. Exocytosis (release) of insulin can occur at the same time from multiple b cells
What is the limitation of an electrical synapse?
Ions can flow bidirectionally, so the postsynapic neuron can cause the presynaptic neurons to depolarize.
What are the advantages of electrical synapses?
It allows for many cells to fire nearly simultaneously It works with out the need for receptors to recognize chemical messengers, signal transmission is much faster
$$$ How does an excitatory synapse affect the postsynaptic membrane potential?
It excites (depolarizes) the postsynaptic neuron and makes it more likely that the postsynaptic neuron will fire an action potential. Ways to depolarize postsynaptic membrane: Bring in Na+ Prevent K+ from leaving
$$$ How does an inhibitory synapse affect the postsynaptic membrane potential?
It inhibits (hyperpolarizes) the postsynaptic neuron and makes it less likely that the postsynaptic neuron will fire an action potential. Makes it more negative in relative to what it was at rest. Prevents us from reacting to every stimulus we get. We can prioritize what we react to.
When Excitatory and inhibitory neurotransmitters hit the target cell simultaneously, what happens? Who wins?
It is a number's game. Whoever is stronger wins.
$$$ What is the function of inhibitory synapses?
It makes it less likely the postsynaptic neuron will fire an action potential. The stimulus has to be strong enough to brought to you conscious. So we don't react to every stimulus we get. This way we can prioritize which stimulus that we want/should react to based on the strength of the stimulus.
What keeps the voltage at -70 mv?
K+ and Na+ Leak channels and ATPase Pumps
**???Presynaptic inhibition of an excitatory synapse (LOOK AT SLIDE WITH DIAGRAM Slide 43)
Modulating axon "H" releases a NT onto "F" axon terminal that activates a 2nd messenger 2nd messenger activates a kinase that phosphorylates voltage gated Ca+2 channels on the presynaptic terminal "F" and inhibits their opening "F" releases less NT
Can proteins pass through the connexons that make up the gap junction?
NOO!
$$$*? A large number of vesicles containing NT fuse with the axon terminal membrane in order to release NT.What happens to all those vesicle membranes?
NT's vesicle membrane material is recycled back into the cytoplasm to avoid axon terminal membrane buildup.
What are the types of chemical synapses?
Neuron to neuron Neuron to muscle Neuron to gland
$$$**? LOSTTTTT How does an axoaxonic synapse stimulate or inhibit an presynaptic axon terminal? PAY ATTENTION TO GRAPH ON STUDY GUIDE
Picture 2: Inhibitory Axon f is trying to depolarize y. H releases neurotransmitter, which bind to F Picture 1 Excitory C is trying to depolarize x. It can't do it by itself. When E came in, the neurotransmitter release was greater. E makes it easier to open Ca+2 Channel. Depending on the NT (Glutamate or GABA), it can increase or decrease the amount of NT released.
Temporal
Same neurons firing over and over
Why are Small-molecule neurotransmitters (NTs) released first?
Small-molecule NT-containing vesicles are localized close to the axon terminal membrane. Released by a low AP frequency Less Ca+2 influx is required to release NT
A fast ligand-gated ion channel when opened, lets in 107 ions/sec and can be__________________________________
Specific for one ion, e.g. Na+ , K+ , Ca+2 or Cl- Specific for ions with the same valence
$$$ What is the difference between temporal and spatial summation?
Summation refers to sum of separate GRADED POTENTIALS Temporal summation is the same neuron firing over and over. 1st one is not done, when the 2nd one comes in. Spatial summation is multiple neurons firing at the same time
$$$ (T or F) EPSPs and IPSPs can occur at the same time on the same neuron
TRUE; stronger one wins
What determines the strength of a graded potential?
The amount of neurotransmitters released and bound to postsynaptic membrane
Why does a cell depolarize when Na+ is coming in and K+ is going out, shouldn't it be in equilibrium?
The cell depolarizes because for Na + the electric and chemical gradient is in the same direction (wants to bring Na+ in) vs the for the K+ ion the chemical concentration wants to take it out, but the electrical charge wants to retain it inside the cell. Because of this more sodium are coming in and less K+ are moving out. So the cell becomes +++ and hence it is depolarized.
What is a Fast response ligand-gated ion channels?
The receptor for the neurotransmitter and ion channel are all in one structure
What are the disadvantages of electrical synapses?
There is a limited number of signaling molecules that can be used. Communication can go both ways (Ex: Ca+2 moves in both direction)
What is a axon hillock?
This is a part of the neuron, between the cell body and the axon, that controls traffic down the axon through summation of excitatory and inhibitory postsynaptic potentials.
True or False: Hearing never stops
True
What is the advantage of an electrical synapse?
Electrical synapses allow rapid communication between adjacent neurons that synchronizes the electrical activity in these cells.
$$$ Explain the difference between an ionotropic and metabotropic ligand-gated receptor.
Fast ligand-gated ion channels are referred to as ionotropic receptors. Slow response G protein-linked receptors are referred to as metabotropic ligand-gated receptors.
Explain the difference between excitatory vs inhibitory axoaxonic synapses?
For an excitatory axoaxonic synapse: -The 1st neuron releases a NT onto the 2nd neuron axon terminal -This stimulates a greater release of NT from the 2nd axon terminal onto the 3rd neuron For an inhibitory axoaxonic synapse: -NT from the 1st neuron decreases NT release from the 2nd onto the 3rd neuron (more later)
$$$ How can you increase the strength of a graded potential?
Increase Action Potential Frequency--->Bring in more Ca+2. ---> Which will release more neurotransmitters which will open up more ion channels.
NTs that open K+ or Cl- channels inhibit depolarizing the postsynaptic membrane. How do they do this?
Increased permeability of K+ causes more K+ to diffuse out of cell (inside becomes more negative) Increased permeability of Clions brings in more (-) charges (inside becomes more negative) Membrane potential becomes more negative (hyperpolarized), harder to depolarize Creates a graded inhibitory postsynaptic potential (IPSP)
