The postsynaptic compartment

Question 1

What are the main functions of postsynaptic spines in neurons?

Answer 1

1. Increase surface area for more synapses.
2. Isolate electrical signals, acting as independent electrical units.
3. Create a biochemical compartment that restricts molecule mobility for localized signaling.

Question 2

Where do excitatory synapses form, and what is the typical density of postsynaptic spines?

Answer 2

Excitatory synapses mainly form on dendrites, and the density of postsynaptic spines is typically around 1-10 per micrometer of dendrite.

Question 3

What is the importance of the spine neck in postsynaptic structures?

Answer 3

The spine neck acts as a resistor, filtering both electrical and chemical signals between the synapse and the dendritic shaft. The length and diameter of the neck determine the resistance.

Question 4

What is the equation for resistance in the spine neck and what do the variables represent?

Answer 4

Rneck=pL/A

P= resistivity of cytoplasm
L= length of neck
A= cross-sectional area of the neck

Question 5

How does the length and diameter of the spine neck affect chemical compartmentalization?

Answer 5

A shorter neck with a larger diameter results in faster compartmentalization of chemicals, whereas a longer, narrower neck slows down chemical diffusion.

Question 6

What is the relationship between the size of the postsynaptic density (PSD) and synaptic response?

Answer 6

Larger PSDs typically contain more receptors, which correlates to a stronger synaptic response.

Question 7

What are the two main types of scaffolding proteins at excitatory synapses and their functions?

Answer 7

1. Primary scaffolding proteins (contain PDZ domains) interact directly with glutamate receptors and are close to the membrane.
2. Secondary scaffolding proteins (lack PDZ domains) interact with primary scaffolds to modulate receptor function.

Question 8

What is caged glutamate, and how is it used to study postsynaptic receptors?

Answer 8

Caged glutamate is a light-sensitive compound that releases glutamate upon exposure to a laser, allowing researchers to activate and study individual spines with high precision.

Question 9

What is the key difference between inotropic and metabotropic postsynaptic receptors?

Answer 9

1. Inotropic receptors directly gate ion channels and provide fast transmission.
2. Metabotropic receptors use G-protein signaling for slower, biochemical transmission.

Question 10

Describe the general structure of ionotropic receptors.

Answer 10

Ionotropic receptors typically consist of 4 or 5 subunits. Examples include:

1. Nicotinic acetylcholine receptor (nAChR): 5 subunits, forming a pentamer.
2. Glutamate receptors (AMPA, NMDA): 4 subunits forming a tetramer.

Question 11

How does the acetylcholine receptor (nAChR) function to open its ion channel?

Answer 11

nAChR has a pentameric structure with a “kink” in the channel. Binding of acetylcholine causes the subunits to twist, opening the channel and allowing ions to flow through.

Question 12

What are the three states of glutamate receptors?

Answer 12

1. Closed
2. Open (rapid ion flow after glutamate binding)
3. Desensitized (receptor remains bound to glutamate but no ion flow occurs).

Question 13

What is the key difference between AMPA and NMDA receptor currents?

Answer 13

1. AMPA receptors allow fast synaptic transmission of sodium (Na+) and potassium (K+), but no calcium (Ca2+).
2. NMDA receptors allow calcium (Ca2+) influx but are blocked by magnesium (Mg2+), requiring depolarization to remove the Mg2+ block.

Question 14

How does magnesium (Mg2+) block NMDA receptors, and how is this block removed?

Answer 14

At resting potential, Mg2+ blocks the NMDA receptor channel. Depolarization of the postsynaptic membrane removes the block, allowing calcium (Ca2+) to enter.

Question 15

What type of ion do GABA-A receptors conduct, and how does it affect the postsynaptic membrane?

Answer 15

GABA-A receptors conduct chloride (Cl-) ions, which hyperpolarizes the postsynaptic membrane, making it less likely to fire an action potential.

Question 16

What is observed in single-channel recordings of GABA-A receptor activity?

Answer 16

In typical recordings, chloride (Cl-) ions move into the cell, causing hyperpolarization. If the membrane potential is made more negative, Cl- moves out of the cell.

Question 17

What is synaptic integration, and how do postsynaptic compartments contribute?

Answer 17

Synaptic integration refers to the summation of excitatory and inhibitory inputs, determining whether the postsynaptic neuron will fire an action potential.

Question 18

How does the structure of the PSD influence synaptic transmission?

Answer 18

The PSD organizes and holds receptors and signaling proteins close to the membrane, directly affecting the strength and efficiency of synaptic transmission.

Question 19

What are nano-columns, and why are they important in excitatory synapses?

Answer 19

Nano-columns are highly organized domains of receptors and scaffolding proteins at the synapse, providing precise alignment of receptors for efficient signaling.

Question 20

How does spine morphology affect synaptic function?

Answer 20

The shape and size of spines influence their electrical and biochemical properties, with larger spines typically associated with stronger synapses and increased plasticity.

Question 21

How does the spine neck act as a filter for synaptic signals, and what are the implications for synaptic plasticity?

Answer 21

The resistance provided by the spine neck filters both electrical signals (reducing back-propagation) and chemical diffusion (isolating biochemical events), which can affect plasticity by compartmentalizing synaptic changes.

Question 22

How do AMPA and NMDA receptors work together in synaptic plasticity?

Answer 22

NMDA receptors allow calcium entry upon depolarization, which triggers signaling pathways that insert more AMPA receptors into the postsynaptic membrane, strengthening the synapse (long-term potentiation, LTP).

Question 23

How has the use of fluorescence microscopy advanced our understanding of spine neck dynamics?

Answer 23

Fluorescence techniques allow measurement of how long it takes for molecules to refill the spine, providing insights into spine neck resistance and its role in signal isolation.

Question 24

Why are PDZ domain-containing scaffolding proteins crucial for receptor localization at excitatory synapses?

Answer 24

These scaffolds organize and stabilize receptors like AMPA and NMDA, ensuring they are precisely positioned for efficient synaptic transmission and plasticity.

Question 25

How can you measure synaptic currents at inhibitory and excitatory synapses, and what do these recordings reveal about synaptic function?

Answer 25

Techniques like patch-clamp recording measure currents by clamping membrane potential, revealing the ionic conductance and receptor function at different synapses.