The presynaptic terminal

Question 1

What does it mean for neurotransmitters to be released in discrete quanta?

Answer 1

Neurotransmitters are released in fixed amounts, each corresponding to the content of a single synaptic vesicle. This release is the basic unit of synaptic transmission.

Question 2

What are spontaneous potentials, and how do they relate to single quanta release?

Answer 2

Spontaneous potentials are mini excitatory or inhibitory postsynaptic currents (mEPSC/mIPSC), which occur without action potentials. They result from the random release of a single vesicle (quanta) at the synapse.

Question 3

What is a miniature postsynaptic response (miniature EPSC)?

Answer 3

It is the postsynaptic response to a single vesicle’s worth of neurotransmitter, resulting in a small postsynaptic potential (EPSC or IPSC).

Question 4

How does the postsynaptic response change depending on the number of vesicles released?

Answer 4

More vesicles released leads to a stronger postsynaptic potential, as the effect of each vesicle’s neurotransmitter release adds up.

Question 5

What is asynchronous release, and why is it important?

Answer 5

Asynchronous release occurs after the main synchronous release, allowing for a more prolonged signaling period, which can modulate synaptic plasticity and communication.

Question 6

What are calcium nanodomains, and how do they influence neurotransmitter release?

Answer 6

Calcium nanodomains are localized high concentrations of Ca²⁺ near calcium channels, triggering neurotransmitter release in vesicles closest to the channel.

Question 7

What buffers affect calcium nanodomains?

Answer 7

Calcium buffers like calbindin reduce the spread of calcium nanodomains, modulating neurotransmitter release.

Question 8

How is neurotransmitter release dependent on extracellular calcium levels?

Answer 8

Calcium influx through voltage-gated channels is crucial for vesicle fusion and neurotransmitter release; higher external calcium increases release probability.

Question 9

Explain the equation
EPP=k[Ca2+]m, where m ≈ 4

Answer 9

This equation describes how the magnitude of the end-plate potential (EPP) is proportional to the calcium concentration raised to the power of ~4, meaning release is highly sensitive to calcium levels.

Question 10

What is caged calcium, and how is it used in research?

Answer 10

Caged calcium is a photoreleasable calcium compound used to precisely control and study calcium’s effects on neurotransmitter release when exposed to light.

Question 11

What role does synaptotagmin play in neurotransmitter release?

Answer 11

Synaptotagmin is a calcium sensor that triggers synaptic vesicle fusion with the presynaptic membrane, enabling neurotransmitter release during exocytosis.

Question 12

What have functional studies of synaptotagmin shown?

Answer 12

Studies show synaptotagmin is critical for rapid, synchronous neurotransmitter release, binding calcium and initiating vesicle fusion.

Question 13

Why does asynchronous release still occur in synaptotagmin mutants?

Answer 13

Other mechanisms, such as different calcium sensors or vesicle fusion pathways, can drive asynchronous release even without functional synaptotagmin.

Question 14

What are the main steps of the presynaptic vesicle cycle?

Answer 14

The cycle includes vesicle docking, priming, calcium-triggered fusion (exocytosis), and retrieval of vesicle membrane via endocytosis.

Question 15

What is dynamin’s role in the synaptic vesicle cycle?

Answer 15

Dynamin is a GTPase responsible for pinching off vesicles from the membrane during endocytosis, allowing vesicle recycling.

Question 16

What are the kiss-and-stay and kiss-and-run models of exocytosis?

Answer 16

In the kiss-and-stay model, the vesicle fuses briefly and stays attached to the membrane, while in the kiss-and-run model, it fuses, releases neurotransmitters, and detaches quickly for recycling.

Question 17

How does excess calcium inhibit endocytosis?

Answer 17

High calcium concentrations can impair the endocytosis machinery, reducing vesicle recycling efficiency.

Question 18

How do low calcium levels facilitate endocytosis?

Answer 18

Lower calcium concentrations support efficient vesicle retrieval, allowing the synaptic vesicle cycle to continue.

Question 19

What is the structure of clathrin, both individually and in complexes?

Answer 19

Clathrin forms triskelion structures, which assemble into a cage-like framework around vesicles during endocytosis.

Question 19

What is the role of clathrin in vesicle retrieval?

Answer 19

Clathrin coats vesicles during endocytosis, helping them bud off from the plasma membrane for recycling.

Question 20

How are clathrin-coated vesicles formed?

Answer 20

Clathrin proteins bind to adaptors at the plasma membrane, forming a coated pit that buds off to become a vesicle.

Question 21

How does vesicle size affect quantal amplitude?

Answer 21

Larger vesicles contain more neurotransmitter, leading to a larger postsynaptic response or quantal amplitude when released.

Question 22

How do different synaptic vesicle populations exhibit differential calcium sensitivity, and what are the functional implications of this?

Answer 22

Vesicles with low- and high-affinity calcium sensors allow for both fast, synchronous release and delayed, asynchronous release, which tunes synaptic responses depending on physiological needs.

Question 23

How are techniques like caged calcium and voltage-clamp used to study neurotransmitter release?

Answer 23

Caged calcium allows for precise control over calcium levels, revealing the kinetics of calcium-triggered exocytosis. Voltage-clamp techniques measure postsynaptic currents to quantify vesicle release dynamics.

Question 24

How does neurotransmitter release contribute to synaptic plasticity, such as LTP and LTD?

Answer 24

Synaptic plasticity relies on changes in the probability of vesicle release, receptor sensitivity, and postsynaptic signaling, which are modulated by activity-dependent calcium signaling.

Question 25

What are the limitations of current models of vesicle cycling (kiss-and-run vs. full fusion), and how might future research address these?

Answer 25

Kiss-and-run provides a faster recovery model, but full fusion may account for larger vesicle sizes and greater neurotransmitter release. Limitations arise from the difficulty in observing real-time vesicle behavior, with future studies possibly using advanced imaging techniques like super-resolution microscopy.

Question 26

What is the role of calcium sensitivity in neurotransmitter release?

Answer 26

Calcium sensitivity determines how likely a vesicle is to release its neurotransmitter in response to incoming calcium. Vesicles with high-affinity calcium sensors require lower calcium levels for release, while low-affinity sensors require higher calcium concentrations, allowing for fast and slow phases of neurotransmission.

Question 27

How do calcium nanodomains regulate synaptic transmission?

Answer 27

Calcium nanodomains are highly localized increases in calcium concentration near voltage-gated calcium channels. These domains tightly control the probability of vesicle release, affecting the timing and synchronization of neurotransmitter release at the synapse.

Question 28

How does calcium influence the probability of synchronous and asynchronous release?

Answer 28

Synchronous release occurs immediately in response to high calcium concentrations, mediated by high-affinity sensors like synaptotagmin. Asynchronous release occurs later, sustained by lower concentrations of calcium, which triggers vesicles with low-affinity sensors.

Question 29

How do different calcium sensors, like synaptotagmin, mediate exocytosis?

Answer 29

Synaptotagmin is a primary calcium sensor that binds calcium ions during depolarization, triggering rapid vesicle fusion and neurotransmitter release. Mutations or removal of synaptotagmin lead to impaired synchronous release and a greater reliance on asynchronous mechanisms.

Question 30

How is neurotransmitter release linked to synaptic plasticity?

Answer 30

Changes in the probability of neurotransmitter release modulate synaptic strength, contributing to synaptic plasticity mechanisms like long-term potentiation (LTP) and long-term depression (LTD). More vesicles released can strengthen a synapse, while fewer can weaken it.

Question 31

How does calcium-dependent neurotransmitter release contribute to synaptic plasticity?

Answer 31

Calcium influx through NMDA receptors or voltage-gated calcium channels can strengthen synaptic connections by increasing vesicle release probability, enhancing postsynaptic responses, and stabilizing these changes in long-term plasticity mechanisms like LTP.

Question 32

How do spontaneous release and miniature postsynaptic potentials (mEPSCs) contribute to synaptic plasticity?

Answer 32

Spontaneous release events contribute to basal synaptic activity and may prime synapses for plasticity. These miniature events, or mEPSCs, reflect single-vesicle release, and changes in their frequency or amplitude can be indicators of presynaptic or postsynaptic modifications during plasticity.

Question 33

How does the size of vesicles influence synaptic strength and plasticity?

Answer 33

Larger vesicles typically carry more neurotransmitter and, when released, cause a greater postsynaptic response (quantal amplitude). This can influence the overall strength of the synapse, contributing to plasticity by affecting how strongly a neuron can signal to its neighbors.

Question 34

How are caged calcium experiments used to study vesicle release?

Answer 34

Caged calcium compounds release calcium in response to light, allowing researchers to precisely control the timing and amount of calcium influx. This technique helps determine how changes in calcium concentration influence vesicle fusion and neurotransmitter release.

Question 35

How do voltage-clamp recordings help in studying neurotransmitter release?

Answer 35

Voltage-clamp techniques hold the membrane potential constant, allowing precise measurement of synaptic currents in response to calcium influx. This method helps isolate and quantify vesicle release events and postsynaptic responses.

Question 35

What are the strengths and limitations of using synaptotagmin mutants to study calcium-mediated vesicle release?

Answer 35

Synaptotagmin mutants provide insight into the role of specific calcium-binding sites in triggering neurotransmitter release. However, compensatory mechanisms, such as upregulation of other calcium sensors, can sometimes complicate interpretation of the results.