An action potential arrives at a presynaptic terminal, but no neurotransmitter is detected in the cleft. Which explanation is most consistent with normal synaptic physiology?
AThe SNARE proteins are permanently fused and cannot open
BThe release probability of individual vesicles is less than 1, so it is possible for no vesicles to fuse on a given spike
CCalcium channels must have been permanently closed due to repolarization
DThe synaptic cleft is too wide for neurotransmitter to diffuse across
Synaptic vesicle release is probabilistic — each docked vesicle has a release probability typically between 0.1 and 0.5 at many central synapses. On any given action potential, it is entirely possible that no vesicle happens to fuse. This is not a failure; it is the normal statistical nature of quantal release. Option A is wrong because SNARE proteins are not 'permanently fused' — they zip and unzip during each fusion event. Option C is wrong because calcium channels open normally during an action potential and then close during repolarization; this is expected and does not prevent transmission. Option D is wrong because the synaptic cleft (~20 nm) is easily traversed by diffusion.
Question 2 Multiple Choice
Botulinum toxin causes flaccid paralysis while tetanus toxin causes spastic paralysis. Both toxins cleave SNARE proteins. What best explains the opposite clinical outcomes?
AThey cleave different SNARE proteins at different synapses: botulinum at excitatory motor synapses, tetanus at inhibitory spinal interneurons
CTetanus toxin works presynaptically; botulinum toxin works postsynaptically
DBotulinum cleaves the vesicle membrane; tetanus cleaves the postsynaptic receptor
Both toxins are SNARE-cleaving proteases, but they target different synaptic populations. Botulinum toxin acts at neuromuscular junctions (peripheral motor synapses), blocking acetylcholine release and preventing muscle activation — hence flaccid paralysis. Tetanus toxin is transported retrogradely into the spinal cord, where it cleaves SNARE proteins in inhibitory interneurons, blocking glycine/GABA release. Without inhibitory input, motor neurons fire uncontrollably — hence spastic paralysis. The lesson: the same molecular mechanism (SNARE cleavage) produces opposite clinical effects depending on which synapses are targeted.
Question 3 True / False
Synaptic transmission is called 'quantal' because each vesicle releases a fixed, all-or-nothing packet of neurotransmitter.
TTrue
FFalse
Answer: True
This is correct. A 'quantum' of neurotransmitter is the fixed package of molecules contained in a single synaptic vesicle — typically thousands of molecules. The quantal nature of release was demonstrated by del Castillo and Katz using miniature end-plate potentials (mEPPs), tiny spontaneous potentials that are integer multiples of a basic unit. The key insight is that release is granular, not continuous: you get 0, 1, 2, or more vesicles releasing, each contributing one quantum to the postsynaptic response.
Question 4 True / False
A stronger (larger-amplitude) action potential will cause more neurotransmitter to be released from the presynaptic terminal.
TTrue
FFalse
Answer: False
Action potentials are all-or-nothing events — a larger stimulus does not produce a larger action potential. The amplitude of the action potential at the terminal does not vary with stimulus intensity. What varies is the firing rate (how many APs per second) and, through other modulatory mechanisms, the release probability. The amount of neurotransmitter released per AP is determined by the local calcium influx, the number of docked vesicles, and their release probability — none of which depend on the AP amplitude itself. This is a critical distinction between graded potentials and action potentials.
Question 5 Short Answer
Why is calcium influx — rather than the action potential voltage change itself — the direct trigger for synaptic vesicle fusion?
Think about your answer, then reveal below.
Model answer: Calcium serves as a chemical second messenger that couples the electrical event (membrane depolarization) to the mechanical event (vesicle fusion). The SNARE machinery is already assembled and primed; what holds it back is a calcium-sensitive clamp. When Ca²⁺ enters through voltage-gated channels and binds synaptotagmin on the vesicle, it releases this constraint and allows the SNARE complex to complete membrane fusion. Voltage alone cannot do this — it only opens the Ca²⁺ channels that deliver the trigger.
This two-step design (voltage → Ca²⁺ → fusion) allows the synapse to be regulated at multiple levels. Release probability can be tuned by changing local calcium concentration (e.g., with drugs that block or enhance Ca²⁺ channels), by changing the distance between channels and vesicles, or by modifying synaptotagmin's calcium sensitivity. If voltage directly triggered fusion, the synapse would lose this flexibility and would be non-modulatable.