Midterm 2

Question 1

How are neurotransmitters packaged into vesicles?

Answer 1

• Proton Pump = creates H+ concentration difference by concentrating H+ inside the vesicle. Active transport, H+ against the gradient, requiring ATP
• Transporter = uses H+ gradient to move neurotransmitters into the vesicle. Passive transport of H+ is coupled with transport of neurotransmitter into the vesicle (antiport).

Question 2

How are neuropeptides transported to axon terminal?

Answer 2

• Neuropeptides are synthesized in the soma, packed into a vesicle, and transported to the presynaptic element by anterograde axonal transport.
• Neuropeptides are found in dense core vesicles.

Question 3

How are neurotransmitters exocytosed?

Answer 3

• V-SNARE and T-SNARE proteins dock vesicles at the active zone.
• Vesicle fuse with the cell membranes when Ca2+ binds to synaptotagmin.
• Exocytosis is triggered by Ca2+ concentration increase inside the cell.
• Voltage gated Ca2+ channel opens during each action potential.
• Large driving force lets Ca2+ inside the cell, triggering exocytosis. Equilibrium potential for Ca2+ ion is very positive compared to the action potential. This serves as the driving force.
• Ca2+ builds up after each action potential, leading to more and more release of neurotransmitters from the presynaptic neuron when continuously fired. The current flowing in postsynaptic neuron will increase.

Question 4

How do we know that chemicals are released at a chemical synapse?

Answer 4

• The vagus nerve, when excited, slows the heart rate
• The vagus nerve associated with Heart1 is electrically stimulated and Heart1 slows.
• The solution that bathes Heart1 is applied to Heart2, and Heart2 also slows.
• This suggests that stimulating the vagus nerve released signaling molecules into the solution.

Question 5

How do we know that Ca2+ is involved?

Answer 5

• If Ca2+ is applied locally near the axon terminal of the motor neuron BEFORE exciting the motor neuron, there is a muscle twitch.
• If Ca2+ is applied locally near the axon terminal of the motor neuron AFTER exciting the motor neuron, there is no muscle twitch.
• Suggests that Ca2+ is needed for presynaptic neuron to stimulate the postsynaptic neuron.

Question 6

Ionotropic Receptor
Metabotropic Receptor

Answer 6

*Postsynaptic neuron can respond when neurotransmitters binds ionotropic or metabotropic receptors

• Ionotropic receptor = Neurotransmitter gated ion channel. Selective ion permeability, bidirectional
• Metabotropic receptor = G-protein-Coupled Receptor that activates via neurotransmitter to receptor binding

Question 7

How are neurotransmitters cleared from the synaptic cleft?

Answer 7

• Selective reuptake and degradation
• Reuptake = recycling used neurotransmitters. Transporters let in neurotransmitters back into the presynaptic neuron. Slow process.
• Degradation = neurotransmitters are broken down by enzymes. Byproducts are reuptaken by transporters. Fast process.

Question 8

Electrical synapse = Gap junction

Answer 8

• Allows ions to pass through. NOT neurotransmitters. Bidirectional, passive, fast process.
• Cardiac muscle, inhibitory networks, development
• Electrical synapse plays a role in synchronized, fail-proof signaling.

Question 9

Neuromuscular Junction (NMJ)

Answer 9

• Because of its accessibility, NMJ is valuable in studies of synaptic transmission

NMJ exhibits fail-proof firing:
* Many vesicles are exocytosed with high concentration of Acetylcholine released
* Junctional folds contain many receptors and concentrate acetylcholine near receptors (easier ligand to receptor binding)

Question 10

Experiments on neuromuscular junction

Answer 10

• There is a delay between excitation of a presynaptic neuron and postsynaptic response
• There are spontaneous depolarization of the postsynaptic neuron (“mini” excitatory postsynaptic potentials). Voltage change is same in magnitude (all vesicles are packed with a similar amount of neurotransmitters). The vesicles get exocytosed by rare, random chance.
• If we know the voltage change after a release of one vesicle, we can calculate the number of vesicles that would be needed to reach an action potential.

Question 11

Action potential vs. Postsynaptic potential

Answer 11

• Action potential = require activation of VOLTAGE gated ion channels on axon
• Postsynaptic potential = require activation of LIGAND gated ion channels on the postsynaptic membrane

Question 12

Reversal Potential

Answer 12

The membrane potential at which the current changes its flowing direction. Equilibrium voltage if only one channel is open. No net current flowing.

*** When a ligand gated channel is open on postsynaptic neuron, current will drive the voltage toward the reversal potential

If the reversal potential is greater than threshold = excitatory
If the reversal potential is less than threshold = inhibitory

Calculated by conducting a series of patch clamp experiments to determine a voltage where current reverses from inward to outward

Question 13

Postsynaptic current is determined by the reversal potential

Answer 13

Excitatory postsynaptic current (EPSC) drives voltage above threshold to reach excitatory reversal potential.

Inhibitory postsynaptic current (IPSC) drives voltage below threshold to reach inhibitory reversal potential.

EPSP + IPSP will drive the voltage lower than the action potential threshold

Question 14

Ionic equilibrium potential

Answer 14

The voltage that would occur if the cell membrane was only permeable to a single ion.

Calculated from the intracellular and extracellular ion concentrations

Can be used to determine if the ion would move in or out of an open ion channel

Question 15

Electron microscopy of excitatory vs inhibitory synapse

Answer 15

Excitatory synapse = asymmetrical and round vesicles

Inhibitory synapse = symmetrical and oval vesicles

Question 16

2 Research Methods

Answer 16

Immunohistochemistry = to detect and localize specific molecule within cell
* Inject molecule or protein of interest into a model organism.
* This substance will cause an immune response.
* Withdraw specific antibodies from the bloodstream.
* Antibodies, marked with fluorescence, can be used as a tool to selectively view the molecule of interest

In Situ Hybridization = to detect mRNA
* mRNA sequence of interest from the neuron can be labeled with fluorescent probe (complementary sequence of nucleic acids)
* Detect and visualize if the cell is expressing the particular gene

Question 17

Typical CNS synapse

Answer 17

• Is NOT fail-proof
• The postsynaptic neuron must summate many inputs to reach action potential
• By summing inputs, the postsynaptic neuron does computations

Question 18

Time Constant
Length Constant

Answer 18

Time Constant = how fast the membrane depolarizes (depends on capacitance multiplied by membrane resistance)

Length Constant = how far the voltage travels down the axon before it decays to zero (depends on membrane resistance divided by internal resistance)

Question 19

Synaptic Strength
* Dendritic spine morphology

Answer 19

• Synaptic strength depends on location because inputs generate an action potential if voltage exceeds threshold at the axon hillock (closer to the axon hillock, easier for voltage to reach action potential)
• Dendrites with long and narrow spine have a large internal resistance. The length constant is small. Synapses on these spine will be weaker
• Dendrites with short and stubby spine have a small internal resistance. The length constant is large. Synapses on these spine will be stronger

Question 20

Where can synapse occur on a neuron?

Answer 20

Anywhere…
* Axodendritic
* Axosomatic
* Axoaxonic

Question 21

Temporal Summation

Answer 21

• Occurs when one presynaptic neuron releases neurotransmitter many times over a short period of time
• Neuron is better at temporal summation if the time constant is large. If it takes a longer time for the neuron to respond, the EPSPs can sum and reach the action potential threshold
• If time constant is small, the EPSPs decay back to rest quickly without summing. Not enough time for summation and the action potential threshold will not be reached.

Question 22

Coincidence Detection

Answer 22

• Coincidence detection = postsynaptic neuron spikes in response to synchronous inputs (reach action potential if multiple inputs occur simultaneously)
• Neuron is better at coincidence detection if the time constant is small. EPSPs can sum and voltage in the postsynaptic neuron exceeds the threshold.

Question 23

Spatial Summation

Answer 23

• Effects of impulses received at different places on the neuron add up so that the neuron may fire when such impulses are received simultaneously
• Neuron with large length constant is able to better perform spatial summation. Because voltage is able to travel down more, EPSPs can sum up together to reach action potential threshold.
• Neuron requires a greater number of spatially summated inputs if the length constant is small

Question 24

In a Pyramidal Neuron: “EPSP amplitudes at the soma are independent of synapse location”

How?

Answer 24

More receptors at distal synapses
* Distal synapses have larger EPSP
* Same amount of glutamate released at all synapse
* Same receptor current at all spines
* Same probability that receptor opens at all spines

Question 25

Shunting Inhibition

Answer 25

• Shunting inhibition occurs when proximal inhibition cancels out distal excitation. The strongest inhibitory neurons occupy the axon hillock.

Question 26

Presynaptic Modulation

Answer 26

• Changing the voltage of presynaptic neuron’s axon terminal by forming axoaxonic synapse at PREsynaptic neuron

Pre-synaptic inhibition = depressed post synaptic potential (less vesicles released)

Pre-synaptic excitation = facilitated post synaptic potential (more vesicles released)