Synaptic Transmission [6] Flashcards
The mechanism of the action potential and the Nernst equation.
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What is electrical synaptic transmission? Name a limitation of this form of intercellular communication (compared to chemical transmission)
Electrical synaptic transmission occurs when electrical current is spread from one neuron to another via gap junctions between cells.
The problem with electrical synaptic transmission is that it cannot provide the same amplification of signal that chemical synaptic transmission can achieve.
Also can only be excitatory, and integration of signals is difficult
Why would electrical synaptic transmission be ineffective at the neuromuscular junction? Is this method of communication important in the mammalian CNS?
For electrical synaptic transmission to work, e.g. provide enough current to depolarize the post-synaptic cell to threshold, the pre- and post- synaptic cells need to be comparable in size. In the NMJ, the presynaptic nerve terminal is dramatically smaller than the postsynaptic muscle fiber it innervates. It could never provide enough current to depolarize the muscle (by 30mV) using electrical synaptic transmission. The NMJ works because of a chemical amplifier
Name examples of electrical synaptic transmission.
- escape reflexes in animal kingdom,
- synchronously firing networks
- heart muscle contraction
- Development of retina, inner ear
- CNS: fear learning, emotional memory in hippocampus
- Contribution to the establishment of (alert) theta rhythms
Name the presynaptic events involved in transmitter release, from the time of the arrival of an action potential to exocytosis
AP arrives at motor nerve terminal (presynaptic cell) → voltage gated Ca+2 channels open → influx of Ca+2 → fusion of vesicle membrane with nerve terminal membrane → synaptic vesicle exocytosis → ACh released into the synaptic cleft.
ACh binds to *ACh Receptors in postsynaptic cell (muscle fiber) → ligand-gated ion channels open → Na+ (and other cations) flow into the muscle fiber → muscle fiber depolarizes to threshold → voltage-gated ion channels open → even more Na+ enters the cells → 2 APs generated, travel in opposite directions to reach each tendon
*ACh Receptor is a Non-Selective Cation Channel
Describe the subsequent presynaptic events involved in cleanup operations, both outside the cell (consider the neurotransmitter molecules) and inside the cell
(consider sodium ions, calcium ions, synaptic vesicles, and neurotransmitter)
- Pre-synaptic Cell:
• Ca2+ ions pumped back out of the nerve terminal
• Post-exocytic synaptic vesicles are retrieved by “kiss-and-run” vesicles (after single action potential) or by full fusion exocytosis (after prolonged stimulation) - Synaptic Cleft: Get rid of excess ACh through simple diffusion, ACh Esterase (most important!) or Reuptake
- Post-synaptic Cell:
• Muscle fiber must extrude the Na+ and Ca2+ ions that entered through ACh-gated channels
• Must also reabsorb K+ ions lost through the same pathway
• Uses Na+/K+ pump and Ca2+ pump located in the cell membrane
How does tetanus toxin act, how does botulinum toxin act?
Botulinum toxin cleaves SNAREs on
Tenanus toxin also acts on
Name the postsynaptic events involved in synaptic transmission.
- Muscle fiber must extrude the Na+ and Ca2+ ions that entered through ACh-gated channels
- Must also reabsorb K+ ions lost through the same pathway
- Uses Na+/K+ pump and Ca2+ pump located in the cell membrane
What is the ‘job description’ for a motor nerve terminal?
Every time an AP arrives from the CNS, you must secrete enough ACh to depolarize the muscle fiber you innervate to threshold for an AP (about 30 mV).
• If you secrete 1 molecule of ACh too little → muscle will not initiate an AP and you’ll get no twitching at all
• If you secrete buckets of ACh → muscle fiber will still only give a single twitch and you’ll have wasted a lot of ACh
Thus, the neuromuscular synapse acts as an all-or-none switch.
Describe how the neuromuscular synapse amplifies the incoming signal in order to depolarize the muscle fiber to threshold for an action potential.
Need to depolarize by 30mV (-80mV to -50mV):
1 Vesicle = 2000 molecules of ACh+
2 ACh+ to activate each ACh Receptor = 1000 ACh Receptors that can be activated per Vesicle
1nV per ACh+ → 1000 ACh+ x 1nV = 1uM
1uM x 1000 ACh Receptors = 1mV of depolarization per Vesicle
1mV per Vesicle x 100 Vesicles = 100mV = Depolarization
What is the safety factor at the neuromuscular junction? Do CNS synapses have safety factors as well? Why / why not?
The motor nerve terminal secretes the contents of a few times more than the minimum number of
synaptic vesicles needed. This safety factor comes in handy during repetitive stimulation, when
the number of vesicles that undergo exocytosis with each stimulus declines
The CNS doesn’t really have a safety factor
When would you see facilitation and synaptic depression?
Both facilitation and synaptic depression occur during repetitive stimulation.
Depression: Reduction of the number of available vesicles during periods of high-frequency activity. Time course: seconds to about 1 minute.
Facilitation: Accumulation of calcium in the presynaptic terminal. Time course: milliseconds to
Describe the basic mechanism that determines whether a synapse is direct (fast) or indirect (slow). Name a typical physiological response mediated by each.
Fast Synapse: Ionotropic (NT directly gates an ion channel)
• Example: Muscle Fiber Depolarization
o ACh binds to nicotinic AChR → opens NSC Channel → Na+ flows in → muscle fiber depolarizes
Slow Synapse: Metabotrophic (NT gates a G-Protein Coupled Receptor and requires the activation of a second messenger)
• Example: Opening K+ channels in the heart
o ACh binds to muscarinic AChR → Activates GPCR → γβ Subunit is released and diffuses to the K+ channel → γβ Subunit binds and opens the K+ channel → K+ exits the cell
Describe the conductance (permeability) characteristics of the channel opened in fast excitation. Define the electrical “driving force.” Define the reversal potential for direct excitation.
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Describe the kind of channel that is opened during fast inhibition in the CNS
Fast synaptic inhibition (often through GABA) acts by opening chloride channels in the post-synaptic membrane. The chloride equilibrium potential is more negative than the threshold potential (it is more negative than some resting membrane potentials) so chloride moving into the cell does not result in an action potential
Why is inhibition often more powerful than one might predict from the size of an individual inhibitory post-synaptic potential (IPSP)?
Membrane potential is determined by the relative permeability of all the participating ions, not the individual amplitudes of the excitatory or inhibitory post-synaptic potentials. A small inhibitory post-synaptic potential can reflect a very large change in ion permeability if the ion’s equilibrium potential is close to the resting membrane potential (i.e. chloride potential)
Define temporal and spatial summation of postsynaptic potentials.
When two presynaptic inputs both synapse on a single neuron, their potentials can be added together and form a larger potential as a significant increase in neurotransmitter is released. If a single input is stimulated twice in succession, the second rise in potential can start rising before the previous action potential has ended. The amplitude of the potentials will summate algebraically to create a potential that is larger than the individual potentials.
Describe the three mechanisms for removing transmitters from synaptic clefts.
- Diffusion: This is common in both the CNS and at the NMJ. Small molecules can diffuse into the large amount of extracellular fluid that is adjacent and contiguous with the synaptic cleft.
- Reuptake: There are many neurotransmitter specific pumps in the presynaptic terminal (NMJ, where reuptake is less important) or the surrounding glia (CNS, reuptake is very important). These pumps move neurotransmitter from the synapse into the cell and then the neurotransmitters must be returned to synaptic vesicles.
- Destruction: This pathway is common at the NMJ for acetylcholine, but rare in the CNS. Acetylcholine esterase is an enzyme that resides in the synaptic cleft and breaks ACh down into choline and acetate, which are not effective transmitters. The choline can then be pumped into the cell and converted back to ACh.
What is a coincidence detector?
a process by which a neuron or a neural circuit can encode information by detecting the occurrence of temporally close but spatially distributed input signals.
What is LTP, what is LTD? How are they involved in learning and memory?
Long-Term Potentiation: LTP
An increase in the synaptic current produced by a synapse after a pairing event.
Long-Term Depression: LTD
A decrease in the synaptic current produced by a synapse after a pairing event.
If you learn anything, the learning happens at the synapses, and is “stored” there. Stronger synapses = LTP = better memory
LTP can neutralize the LTD and vis versa- you can learn and unlearn things!
Define and describe the mechanism of Facilitation
Facilitation is due to the residual calcium inside the nerve terminal, left over from previous action potentials that has not yet been able to be pumped out of the cytoplasm
due to stimulation frequency.
Define and describe the mechanism of Synaptic Depression
During repetitive stimulation, the nerve terminal starts to run out of releasable vesicles: it can’t replenish the synaptic vesicles from its reserves fast enough to keep up with demand. As a result, the number of quanta released during each synaptic potential will decrease.
Synaptic depression is due to depletion of releasable synaptic vesicles
How does the NMDA receptor work as a coincidence detector?
The NMDA receptor requires two separate signals occur simultaneously in order to conduct and thus is a coincidence detector. Glutamate released from the presynaptic cell must bind the channel and a post-synaptic action potential must depolarize the membrane enough to electrically force the Mg out of the pore. This allows calcium to influx into the cell.
Calcium ions in the post-synaptic cell strengthen the synapse by causing the insertion of additional AMPA receptors into the post-synaptic membrane. Increased AMPA receptors allow the neuron to respond more strongly to the same amount of released neurotransmitter.
How can activation of NMDA receptors lead to synaptic strengthening? How might such a mechanism lead to behavioral associative conditioning?
When NMDA receptors are activated and calcium flows into the cell, the cell is stimulated to make NO, which then diffuses backwards across the synapse. The presence of NO potentiates neurotransmitter release, i.e. the pre-synaptic cell secretes more quanta of transmitter.
This mechanism can be used to develop behavioral associative conditioning by pairing conditioned and unconditioned responses together (think Pavlov’s dogs, ring a bell and salivate). The weak synapses can be strengthened by pairing the bell (weak input) and meat (strong input). The key to pairing is coincidence.
