From Action Potentials to Synapses and Circuits Flashcards
The opening of what causes the generation of axon potentials?
Action potentials are generated in an axon by the opening then closing of two types of voltage-gated ion channels
- Voltage-gated sodium channels (VGNC)
- Voltage gated potassium channels (VGKC)
Which of the two voltage gated channels opens first in an action potential?
Sodium channels open first, followed by potassium channels later
The permeability of the membrane to both types of ions rises markedly during an AP, just at slightly different times
Describe the ion channels at each stage of the action potential:
RMP
Threshold/Depolarization
Repolarization
AHP (Hyperpolarization)
RMP
RMP
Na: channels closed
K: channels closed
Threshold/Depolarization
Na: channels open
K: channels closed
Repolarization
Na: channels inactivating
K: channels open
AHP (Hyperpolarization)
Na: channels inactivated
K: channels open
RMP
Na: channels closed
K: channels closed
What are the two distinct gates on VGNCs and their functions? AKA What causes the spike in depolarization/membrane potential?
- Activation gates: opens rapidly in response to depolarization but are closed at resting potential
- Inactivation gate: starts open, then closes
After the threshold is reached, VGNC open rapidly (a single open channel produces extra depolarization that causes nearby VGNCs to open)
The channels inactivate, closing themselves
Compare the speed of VGNCs and VGKCs opening and closing
VGNCs open very quickly after the threshold is reached, but VGKCs open very slowly after the threshold has reached depolarization, then they slowly close after the membrane repolarizes
Compare the number of gates in VGNCs and VGKCs
VGNCs have two gates (Activation and inactivation gates)
VGKCs have one gate (Activation gate)
- the activation gate on VGKC respond to the membrane potential crossing threshold, but only after a delay
- VGNCs open before VGKCs do
What drives repolarization?
The increased permeability (as a result o VGKCs opening) drives repolarization (making the membrane potential more negative back to RMP again)
Is the following an example of a positive or negative feedback loop?
Every VG Na+ channel that
opens leads to more
depolarization, increasing
the likelihood that more VG
channels will open.
POSITIVE FEEDBACK LOOP
- as more Na channels open, it causes even more to open
- builds upon it
- depolarization is an example of a positive feedback
Is the following an example of a positive or negative feedback loop?
Every VG K+ channel that
opens leads to repolarization,
increasing the likelihood that
more VG channel activation
gates will close once again
NEGATIVE FEEDBACK LOOP
- brings back to the original condition
- stops the original stimulus and restores the original conditions
- repolarization is an example of negative feedback
What are the two components of action potential refractory periods?
- Absolute refractory period
- Relative refractory period
What is an absolute refractory period?
A second AP CANNOT be generated/triggered no matter how strong the stimulus is
If you generate an AP, for a certain period of time, even if you recreate a stimulus that was even stronger than the previous, you would not get another AP = ABSOLUTE REFRACTORY PERIOD = AGAINST GENERATING ANOTHER AP
What is a relative refractory period?
Relative refractory period starts immediately when the absolute refractory period ends
In this period, a larger than normal stimulus can trigger a second AP but only AFTER the absolute refractory period is over
How do action potentials propagate down the axon?
The action potential itself does not travel, it just generates action potential after action potential down the axon
Depolarization phase creates huge depolarization in VGC
Depolarization spreads within the membrane, bringing the next section to the membrane to threshold, VGCs open and generate another AP (positive feedback loop)
This keeps going in both directions of the axon down either side
Greater potential decays as it spreads from where it was generated (Degrading)
Why do action potentials only spread in one direction although they technically diffuse in both directions?
Because of the REFRACTORY PERIOD and the SODIUM CHANNEL INACTIVATION GATES, this prevents action potentials from being generated in the direction they came from - they will only spread/propagate on the distal side far from the initial segment of AP
Refractory period - prevents another AP from being generated (grace period)
Inactivation gates have not reset so another AP cannot be generated (even if the activation gates react, the inactivation gates will not)
What explains the unidirectional spread of action potentials?
- Refractory period
- Sodium channel inactivation gates
What is the purpose of myelination?
Myelination increases conduction speed for action potentials
Myelination enhances conduction velocity in skeletal muscles and neurons = axons become more energy efficient
Provides a form of electrical insulation, enhancing the spread of potentials and producing saltatory propagation
What is saltatory propagation?
Saltatory propagation is when the action potentials “jump” from node to node
The fatty myelin wraps the axon and removes the leak channels, therefore technically NO ACTION POTENTIALS can occur in the myelinated sections of axons because there are no leak channels
Only place that ions are moving in and out are at the nodes!!
What is a node?
Space on an axon that is not myelinated
How does myelin speed up action potentials?
More charge stays inside a myelinated axon, so potentials spread further and quicker
- myelin prevents action potential from leaking out
- fatty myelin wrapping the axon removes the leak channels = no leaks and depolarization can spread further and quicker
What are synapses?
Connection points for neuron circuits
- meeting point between two cells and consists of two cellular compartments
Site in which an action potential is converted to a chemical signal, which is then converted to a graded potential
Describe the process from graded potential -> action potential and back
Graded potentials start at dendrites/cell bodies generating depolarization
If the depolarization is strong enough at the axon hillock, it generates an action potential down the axon
Axon terminal marks a synapse where the action potential is converted to a graded potential in the next neuron
This process repeats… And this is how electrical/chemical signals can travel
What are the two cellular compartments of synapses?
Presynaptic specialization (axon terminal)
[Synaptic cleft - extracellular]
Postsynaptic specialization (dendrite/soma)
What is the presynaptic specialization (Axon terminal)?
End of an axon containing vesicles with neurotransmitters
- at the end of a neuron
- contains neurotransmitters to be released at the active zone (end membrane of the neuron/axon terminal)
What is the synaptic cleft?
A very small gap between the end of a neuron and the next neuron
What is the postsynaptic specialization (Dendrite/soma)?
The dendrite/soma of the next neuron
- contains local membrane proteins opposed to the active zone
- respond to the neurotransmitters being released
- may contain receptors (ligand-gated)
What are axon terminals?
Compartments that are specialized to release neurotransmitter from synaptic vesicles in response to an action potential
What kind of voltage gated channel does an active zone have?
Has VGCC (calcium) as opposed to VGNC (sodium)
What role does calcium have at the axon terminals?
Calcium is in charge of the biochem that occurs = the link between electrical signaling and biochemical signaling
Catalyzes the fusion of vesicles with the membrane at the active zone
(vesicle fusion machinery specialized proteins)
Ca2+ triggers rapid exocytosis of neurotransmitters
Even with a very strong depolarization, there is still a strong tendency to bring calcium into the axon terminal so AP depolarization can be converted into vesicular release of chemicals
What would happen the amount of NT released from a synapse if a toxin blocked VGNC activation?
If the sodium voltage gated channels cannot open, then the action potential cannot be propagated, therefore it would not make it to the axon terminal
= LESS neurotransmitters released from the synapse
What would happen the amount of NT released from a synapse if a toxin blocked VGKC activation?
If the potassium voltage gated channels cannot open then there would be continuous depolarization
The membrane would not repolarize or repolarize quickly, therefore keeping the membrane depolarized (VGCCs stay open)
Causes there to be more neurotransmitters at the axon terminal
= MORE neurotransmitters released from the synapse
What would happen the amount of NT released from a synapse if a toxin inserted artificial Ca2+ channels into the axon terminal?
inserting artificial Ca2+ channels would accelerate exocytosis, therefore releasing more neurotransmitters from the synapse because there is more calcium in the pre-synaptic to aid the release of NT
= MORE neurotransmitters released from the synapse
What would happen the amount of NT released from a synapse if a toxin destroyed vesicle releasing machinery proteins?
if the vesicle releasing machinery proteins (involving Ca2+) were destroyed, then there would be less neurotransmitters released from the synapse
If the vesicle releasing machinery proteins are destroyed then fewer NT will be released from the vesicles
These proteins aid the release of NT so without them (or having them destroyed) would lead to a decrease of release
Mechanism for vesicles to fuse isn’t there so there are fewer NT being released
= LESS neurotransmitters released from the synapse
What neurotransmitter is often released from the axon terminal (most common)?
Acetylcholine
Describe the process in which NT released from the pre-synaptic end go into the synaptic cleft and to the post-synaptic
Neurotransmitters released into the synaptic cleft bind to the post-synaptic neurotransmitter receptor proteins
- Neurotransmitter (a small molecule) is released from the pre-synaptic axon terminal and into the synaptic cleft
- Molecules travel across the synaptic cleft to the post-synaptic end where there are NT receptors (ligand-gated ion channels)
- Molecules bind to the receptors and chemically gated Na+ channels open
- PSP generation (and spread)
What is a post-synaptic potential (PSP) and what causes it?
Post-synaptic potentials are graded potentials that occur when neurotransmitters are released
Ligand-gated ion channels respond to the release of NTs and produce (graded) post-synaptic potentials
What are the two parts of a PSP?
- Latency
- Slow return to baseline
What is latency in a PSP?
Latency describes the delay before the PSP starts as the time taken for vesicle release (plus transmitter diffusion)
Latency is the period of time where nothing is occurring before the PSP, its the delay that allows for vesicle release and transmitter diffusion across the synaptic cleft
Then there is a fast rise in membrane potential
What is the slow return to baseline in a PSP?
Slow return to baseline describes the gradual removal of NTs from the synaptic cleft into the post-synaptic end
What are the two types of post-synaptic potentials?
Excitatory (EPSPs)
Inhibitory (IPSPs)
What is an excitatory post-synaptic potential? (EPSP)
channels open or tend to move the membrane potential towards the AP threshold (EXCITATORY)
- involves receptors that INCREASE Na+ permeability so that the membrane potential can depolarize to reach the threshold and cause an AP
What is an inhibitory post-synaptic potential? (IPSP)
receptor/ligand gated ion channels create channels in ion permeability to keep the membrane potential below AP threshold (INHIBITORY)
- involves receptors that INCREASE K+ or Cl- permeability so that the membrane potential stays negative and does not reach the threshold for an AP
Increasing Na+ permeability is associated with:
EPSP or IPSP?
EPSP - EXCITATORY
- moving the membrane potential towards AP threshold for depolarization
Increasing K+ (or Cl-) permeability is associated with:
EPSP or IPSP?
IPSP - INHIBITORY
- keeping the membrane potential below AP threshold
What is the difference between an action potential and a post-synaptic potential?
An action potential requires activation of voltage-gated ion channels
Postsynaptic potentials require activation of ligand-gated ion channels on the postsynaptic membrane
The size of a post-synaptic potential is affected by _____________________
The number of ion channels that open and thus pass current
Since post-synaptic potentials can be different magnitudes, that implies that they must be GRADED POTENTIALS
What are the two main ways larger potentials can occur?
More receptors available
= higher density of receptors means that there is more permeability of the NT and more action potentials can be generated
Higher concentration of ligand (neurotransmitter) available
= more NT being released means that more action potentials can be generated
What is summation of graded potentials?
Adding together graded potentials if they spread into the same patch of membrane
Two or more EPSP added together can bring the axon hillock nearer to threshold - triggers the neuron to fire an AP
Adding an IPSP to EPSP(s) can subtract from the depolarization caused by EPSPs, inhibiting/preventing the AP from being fired
Every graded potential will spread away location it was generated, getting weaker but definitely spreading
True or False?
True!
If a neuron has more than one synapse receiving graded potentials that can all spread, these can be summated (Added on top of each other)
There are two types of summation: what are they?
- Spatial summation
- Temporal summation
What is spatial summation?
The addition of post-synaptic potentials coming from TWO DIFFERENT SYNAPSES
When you get two axon terminals generating two PSPs at the same time and overlapping, these two PSPs activate on the same axon and can be added together!
= two spreading PSPs overlapping in space, and thus adding their depolarizations
What is temporal summation?
The addition of CONSECUTIVE PSPs GENERATED BY THE SAME AXON
- there will be a slight delay between PSPs because of the refractory period
= two spreading PSPs generated by two APs from the same presynaptic axon terminal overlap in time
Between graded potentials and action potentials, which one can summate and which one cannot?
Graded potentials can SUMMATE
but
Action potentials CANNOT = They are ALL OR NONE
If the summation of two PSPs results in zero net change, what kind of PSP was it?
It must have been SPATIAL PSP
There must have been an excitatory EPSP and inhibitory IPSP that was generated at the same time from two different axons and CANCELLED EACH OTHER OUT
What are metabotropic receptors?
Metabotropic receptors are receptor proteins that alter the activity of separate ion channels through biochemical signaling, an indirect mechanism for changing membrane potential
How do metabotropic receptors differ from ionotropic receptors?
Ionotropic receptors are ion channels, a direct mechanism for changing membrane potential
Metabotropic receptors are receptor proteins that alter the activity of separate ion channels through biochemical signaling, an indirect mechanism for changing membrane potential
Ex: secondary intracellularly-gated ion channel
True or False: All receptors are ion channels
FALSE!
Some receptors are ion channels, while others are membrane proteins that indirectly activate channels
Match the neurotransmitter with its type of PSP generated and/or the division of the nervous system in which it is found:
Adrenaline
Autonomic nervous system (sympathetic)
“fight or flight”
Match the neurotransmitter with its type of PSP generated and/or the division of the nervous system in which it is found:
Noradrenaline (norepinephrine)
Autonomic nervous system (sympathetic)
“fight or flight”
Match the neurotransmitter with its type of PSP generated and/or the division of the nervous system in which it is found:
Gaba
Mostly central nervous system
- makes IPSPs
Match the neurotransmitter with its type of PSP generated and/or the division of the nervous system in which it is found:
Acetylcholine
Autonomic nervous system (parasympathetic)
“rest and digest”
& at neuromuscular junctions (NMJs)
Match the neurotransmitter with its type of PSP generated and/or the division of the nervous system in which it is found:
Glutamate
Mostly central nervous system
- makes EPSPs
What are agonists and antagonists in the nervous system?
These are drugs that activate or block neurotransmitter receptors
What is an agonist in the nervous system?
A drug that MIMICS the action of an endogenous neurotransmitter - ACTIVATES RECEPTORS
= leads to ENHANCED CELLULAR ACTIVITY
What is an antagonist in the nervous system?
A drug that BLOCKS the activation of a neurotransmitter receptor
= leads to BLOCKED CELLULAR ACTIVITY
Some anticonvulsant drugs (drugs which are used to reduce excessive neuronal
activity occurring during epileptic
seizures) bind to (ionotropic) glutamate
receptors, which produce EPSPs.
Are these glutamate-receptor targeting anticonvulsant drugs acting as agonists or antagonists?
- reduces excessive neuronal activity that produces EPSPs
- must prevent excitation
ANTAGONIST
- antagonize the site which produces EPSPs
- bind to the site so that endogenous NT cannot bind to the receptor
How are synaptic vesicles reformed?
ENDOCYTOSIS
Both synaptic vesicles and NTs are recycled by the axon terminal
Exocytosis of NT causes loss of vesicles
- vesicles fuse with pre-synaptic membrane (exocytosis)
- vesicles reform (endocytosis) so they can be refilled before it can go through NT release again
How is dopamine (serotonin and norepinephrine) recycled?
direct reuptake of molecules by axon terminals to stop PSP from being constantly generated
- get NT back into axon terminal and into vesicle without having to resynthesize it
How is glutamate and GABA recycled?
astrocyte mediated recycling (with the help of the astrocytes)
How is acetylcholine recycled?
degradation and reassembly
- doesn’t directly get taken up by axon terminal or glial cells
- gets broken down by acetylcholinesterase
- no longer work as a neurotransmitter
- stops PSP and gives time to get choline back in the vesicles
Cocaine is a potent inhibitor of the
Dopamine Transporter protein
(DAT), found on the axon terminal.
Many anti-depressant and anti-anxiety drugs are ‘selective serotonin
reuptake inhibitors’ (SSRIs) which block the function of the equivalent transporter protein for a related
neurotransmitter, serotonin.
What would these drugs do to the amount of NT in a synaptic cleft and therefore the size/duration of graded potentials occurring at that synapse?
There would be an excess of NT in the synaptic cleft and the graded potentials would be constantly generated since the dopamine transporters that take dopamine from the synaptic cleft back into the axon terminals have been inhibited
The same could be said about serotonin
- constantly state of HAPPINESS!!
What are pools of neurons?
Neurons in the nervous system are grouped into pools that connect to form specialized neural circuits
What are local connections and what are projections?
Local connection = within a region
Projection = distant regions
What is neuronal circuit convergence?
One post-synaptic neuron receives and summates many different inputs
- many axons converging onto one post-synaptic neuron
What is neuronal circuit divergence?
One pre-synaptic neuron shares its outputs with more than one neuron
- start with one neuron and then it splits/divides into more than one neuron (sharing info)
What is neuronal circuit parallel processing?
Many post-synaptic neurons receiving and passing on the same information to different places
What is neuronal circuit recurrence?
A postsynaptic neuron has a divergent pathway that synapses back on its presynaptic partner
A -> B -> C + A
What is recurrent excitation?
When the divergent pathway excites the pre-synaptic partner
What is recurrent inhibition?
When the divergent pathway encounters an inhibitor and cannot excite the presynaptic partner
