Synaptic transmission: Presynapse Flashcards
There are —- neurons in human brain and —- synapses.
- 80 billion
- 100 trillion
Presynaptic terminal:
- Usually end of axon, but doesnt need to be. Can be en passant synapse where axon has a bulbous spot and keeps going. AP propagate and have many synapse along the axon.
Chemical synapse event sequence (8):
- AP invades terminal
- Depolarization of membrane causes the opening of presynaptic calcium channels
- Calcium enters terminal
- Rise in calcium is sensed by a molecular “calcium sensor”
- Vessicle filled with NT fuses with membrane
- NT is released in the synaptic cleft and binds to postsynaptic receptors
- Activation of postsynaptic receptor results in movement of ions in or out of cells (usually Na+ enters postsynaptic cell)
- Membrane potential of cell changes accordingly.
3 Main advantages for chemical synapse: Amplification
A decaying electrical signal is transformed into the relese of diffusible molecules. Amplification occurs by
1. release of numerous transmitter molecules
2. binding to many receptors
3 Main advantages for chemical synapse: Variety of end effects (4)
- Highly adaptable. You can modify what ion moves through for efficacy, and potency. There are also many proteins involved to modulate conductance and number of ion channels and vesicles and how easily they release.
- Excitatory or inhibitory (not both at the same synapse)
- Ionotropic and metabotropic
- A range of relatively fast to slow effects
3 Main advantages for chemical synapse: Probability of transmission (3)
What + ex + plasicity
- For every action potential invading a terminal, there is not always release of NT- another point of modulation. This introduces a bit of randomness to the system and is thought to be important for modulation and varied outputs from a neural circuit.
- Ex: same synapse in brain take 10 AP to cause NT release while other are 100% faithful and only take 1.
- Plasicity: synapse change in strengths alot through probability of release
Katz and Miledi’s experiment: Ca2+
- Used giant squid axon synapse and TTX a VG-Na+/K+ channel blocker, and found out that when you block either two, you still get postsynaptic response even though weird looking as K+ can’t respolarize
- They observed that presynaptic terminals treated with tetrodotoxin (which blocks Na+ channels) could still produce a peculiarly prolonged type of action potential. The explanation for this surprising finding was that current was still flowing through Ca2+ channels, substituting for the current ordinarily carried by Na+ channels
- The presence of calcium ions in the external medium is required to make depolarization effective. If one progressively reduces the calcium concentration, or adds a <competitive> ion such as magnesium or manganese in increasing amounts, depolarization becomes less and less capable of accelerating the discharge rate of miniature potentials above their resting frequency. Over the last six years, experiments by Miledi and myself have led us to conclude that external calcium is the only immediate ionic requirement for depolarization to evoke transmitter rel e a s e.</competitive>
Katz and Miledi’s experiment: threshold (4)
used what + what they did + what they found + explain graph
- They recorded presynaptic AP by stimulating and seeing postsynaptic response. When the presynaptic AP gets smaller, postsynaptic membrane is smaller bc neurotransmission is smaller.
- Shows that there is a small threshold for chemical neurotransmission to occur. When you make small presynaptic not robust enough, Ca2+ VG will not open and thus no transmission. Lose AP when smaller then 45
These graphs show changes in pre- and postsynaptic potentials after adding TTX over time:
TTX + 7 min (Graph 1):
The presynaptic spike (large peak) is still visible but smaller because Na⁺ channels are partially blocked.
Postsynaptic potential (smaller peak) persists, indicating some transmitter release.
TTX + 14 min (Graph 2):
The presynaptic spike further decreases, but there is still sufficient depolarization for transmitter release, generating a postsynaptic response.
TTX + 15 min (Graph 3):
The presynaptic spike is almost eliminated, leading to a much smaller postsynaptic response.
TTX > 15 min (Graph 4):
The presynaptic spike is fully blocked, meaning there’s no postsynaptic potential. This suggests no neurotransmitter release.
NMJ (2)
WHAT + PROCESS
- motor neuron in SC goes out to peripheral NS and innervates muscle
- Release Ach - binds to nicotinic-Ach receptor (cationic). - significant depolarization turns on VG- Na+ channel - Muscle cell fire AP and contracts
Endplate potential (EPP) (2)
What + how to measure
- EPSP at NMJ
- You will not see EPP in normal AP recording so you add curare a nicotinic Ach receptor blocker. The EPP is reduced below threshold and doesnt generate AP. We now have direct measure of the receptor’s influence on the membrane potential.
- the EPP is a dotted line because you wouldn’t see it if the muscle fired an actional potential. You would only see the action potential because the EPP is large enough for Nav to reach threshold and cause the AP. If you put on TTX to block Nav then you would see the full EPP (the dotted line) which is mediated by nicotinic channels. Does that clarify it for you?
What does an excitatory endplate potential and excitatory current look like?
Electrophysiologist can either measure voltage or current. These are two different ways of looking at the same phenomenon, in this case, the synaptic event. If one is measuring voltage, they will measure ——-. If one is measuring current, they will measure ——. You don’t need to understand the electrophys any more than that.
- an end plate potential or a post synaptic potential
- an end plate current or post synaptic current
Quantal synaptic potentials (2)
What it is + experiment
- small EPP that happen spontaneously without any presynaptic stimulation
- Katz and his colleagues used a technique involving a solution with low calcium and high magnesium concentrations to reduce the size of the endplate potential (EPP) in muscle fibers and compare it to the miniature endplate potentials (MEPPs). They found that under these conditions, the EPP was drastically reduced and approached the size of the MEPP. Remarkably, the smallest measurable EPP (above zero) had the same magnitude and shape as the MEPP, leading them to hypothesize that MEPPs represent a “quantum” of neurotransmitter release, corresponding to a single vesicle of acetylcholine. Larger EPPs, therefore, consist of multiple quanta, with the smallest EPP being equivalent to one quantum, providing evidence for the quantal nature of synaptic transmission.
Explain this experiment:
the stimulus is stimulating the motor axon to cause a presynaptic AP and cause neurotransmitter release. The responses that follow are the EPPs of different quantal sizes (one vesicle, two vesicles etc).
If you depolaruze the motor axon terminally directly (electrically), you can show that chemical transmission does not rely on:
Na+ or K+
Explain this graph:
Under normal circumstance, Na+/K+ trigger AP by allowing VG-Ca2+ channel for Ca2+ entry. When you have 0 extracellular Ca2+ there is no Ca2+ able to enter the nerve terminal so no synaptic transmission. High extracellular Ca2+ results in alot of transmitter release and there is a greater DF for Ca2+ to go in. Low Ca2+ is in the middle.
Explain this graph:
Explain the ca2+ and chemical synaptic transmission time relationship
The time course of Ca2+ influx explains the delay in chemical synatic transmission. Ca2+ influx to vessicle release is very fast because the Ca2+ channels locate very close to the vessicles. The slowest part in how the brain work is the chemical transmission: diffusion + binding
The cone snail (2)
what + the types
Contains a mixture of conotoxins that act on the neuromuscular junction of its prey to paralyze them.
Omega conotoxin: presynaptic ca2+ channels
Alpha and Psi conotoxin: block postsynaptic NAch receptor
Mu conotoxin: bloacks Na+ channels to prevent muscle AP
Synaptotagmin
Calcium sensor that once bound, conformation change for membrane to bind
VG calcium has proteins that:
physically connect it to vessicles
Snare complex (2)
what they do + contains
- coil up together and bring 2 membrane close together “Dock”
- SNAP- 25, Syntaxin, Synaptobrevin (VAMP)
Explain the steps of vessicle docking (5)
- Vessicle comming to dock in the active zone
- Guide to plasma membrane spontaneoulsy
- SNARE complex coil tgt and bring membrane close together
- AP occurs
- Ca2+ causes fusion
Synaptotagmin is not —— but it is the ——.
- in the core zippering complex
- Ca2+ sensor for the fusion event to occur
The bacterial clastridium botulinum
Relax paralyze face muscle by snipping up snare complex so no chemical transmission
Glutamate vesicular transporter (VGlut 1, 2 and 3)
Vessicle have vessicular proton pumps (VATPase) so very acidic as it pumps protons into vessicles, Ph~5. VGlut moves 1 glutamate molecule into vesicle in exchange for one proteon. Cl- can move in either direction and there are Cl- channels to maintain Cl- homeostasis.
Glutamate and GABA are known as
not neuromodulator but fast acting NT with ionictropic channels
Neuromodulator (2)
Role + includes
- squirted out to ECM, modulate inhibit/excite neurons
- Includes: dopamine, EP, NE, Ach, 5-HT
Why so many excitatory NT neurons?
~90% of neuron are excitatory ( glutamate) and 10% are inhibitory
Easier to turn system off then to excite in specific way. Ex: neuron receive 100 inputs, alot are excitatory from all sort of brain area, some has not alot of GABA that can turn off
