Neurobiology Review Questions

In a stereotypical NMJ, what is the chain of events that happens between an action potential arriving at the synaptic bouton that results in EPSP or AP propagation in the muscle fiber?

AP arrives, causing Na+ channels to open and depolarize axon terminal membrane, causes voltage gated Ca 2+ channel to open, that enter the cell trigering fusion of aCh vesicles, Ach diffuses across synaptic cleft and bind to receptors on postsynaptic membrane, which causes depolarization of post to fire an action potential

In what situation would the driving force on an ion be equal to zero?

If the membrane potential is equal to the equilibrium potential of that specific ion.

What are 2 important kinds of information that you can get from an in intracellular recording that you can't get from an extracellular recording?

In intracellular recordings, you can measure the membrane potential inside of the cell, intracellular recordings also tell you the exact response of one cell. With extracellular recordings, signals of surrounding cells can be picked up which will throw off the trace of action potentials you are getting.

What are 2 important differences between the voltage-gated sodium and potassium channels that underlie the action potential?

Inactivation and activation of voltage gated sodium channels are two separate mechanism but both relate to the membrane potential of the cell. Potassium voltage gated channels have a slight delay when they open (why they are called delayed rectifiers)

How would you modify external calcium concentration to make a neuron less excitable? What is thought to be the underlying mechanism for this decrease in excitability?

Increase external calcium concentration; Because there are calcium activated potassium channels so if there is more calcium then you would have more potassium which would hyperpolarize the membrane even more making the neuron less excitable, this makes slow AHP longer

A squid giant axon conducts spikes at about 25 meters/sec. The spike (not including the undershoot) lasts about 1 msec. Over what distance along the giant axon does the spike spread?

0.025 meters? I dunno

What is the difference between a "gate" and a "selectivity filter" as these terms refer to membrane channels?

A gate can allow any ion to pass through when it is open whereas a selectivity filter is selective for certain ions only letting those ones through

Which is faster, and AMPA channel or an NMDA channel? What are 2 other important differences between AMPA and NMDA receptors?

AMPA channel; NMDA channels are not active at lower membrane potentials because glutamate cannot flow through them and NMDA channels have a magnesium block.

What are 2 differences between graded potentials and action potentials?

Action potentials are all or nothing whereas graded potentials can be summed. Graded potentials can also be excitatory or inhibitory.

What do we mean by the term "agonist" when referring to synapses? Which ACh-mediated synapses are faster, nicotinic or muscarinic? Which are ionotropic, nicotinic or muscarinic?

An agonist is a substance which initiates a physiological response when combined with a receptor (increases activity of synapse) Cholinergic (receptors bind AcH): - Nicotinic synapses are faster; nicotinic synapses are ionotropic - muscarinic are metabotropic.

Why must voltage be clamped in order to accurately measure the membrane channel currents that underlie the action potential?

Because you need to understand capacitance and in order to do so you need to keep the other variables of Ohm's law constant

Imagine that you are able to insert whatever channels you want into a neuronal membrane. What 2 types of channels you could insert produce neuron slow after-hyperpolarizations (slow AHPs), such as those seen in frog spinal motor neurons?

Ca activated K+ channels (slow AHP) and Small K channels

Describe the fundamental differences between human NMJs and crustacean NMJs. Why is it useful to study a crustacean NMJ, even though it is so fundamentally different from a human NMJ?

Crustaceans: Each fiber can be innervated by multiple neurons in crustaceans Summation response of end plate potentials (don't have action potentials)

What information could you get from an isolated patch recording (inside-out or outside-out) that you couldn't get from a whole-cell patch recording?

For an isolated patch recording, you have access to the electrical signaling of a small area of membrane and a couple specific ion channels where as the whole cell records information about the cell as a whole not honing in on anything specific.

What is the evidence that a large fraction (perhaps 40%) of sodium channels are inactivated in a membrane at resting potential?

From an experiment where peak sodium current is plotted against the potential during the prepulse; here at -65 (resting potential) only 60% of gates are open; H ordinance

What causes the brief capacitive current pulse as the membrane potential is stepped to a new command voltage? Why the does the capacitive current end so quickly?

If the clamp ampifier is capable of delivering a large amount of current, the membrane is able to be changed rapidly so you see this brief pulse. The current ends so quickly because it just the effect of the amplifier, there are no other factors at that time. After the capacitive current you have the leak current which is due to the flow of potassium and chloride ions.

What is an inside-out patch recording useful for? What is an outside-out patch recording useful for?

Inside out: you can look at ion channels Outside out: you can apply different chemical ligands to the outside surface of the cell and see how it reacts.

What is an advantage of intracellular dye injection over Golgi staining of neurons?

Intracellular dye injection stains one cell where golgi staining of neurons dyes a small patch of several neurons.

In very simple words, what does the Nernst equation tell you. Yes, it tells you the equilibrium potential for an ion, but what does that really mean?

It essentially tells you the driving force for specific ions and how easily ions will move at different membrane potentials.

What is the major advantage of using a non-invasive neural recording technique? What is a disadvantage?

Non invasive neural recording techniques are awesome because you can study neurons in a human when they are alive and functioning. A disadvantage is that the recordings are not super time efficient. You are not getting a live look at what is happening at that exact moment.

Why would such slow AHPs be useful to the neuron? In other words, how do slow AHPs modify temporal spiking patterns in a neuron?

Relative refractory period so you need a greater than normal stimulus in order to generate an action potential during the AHP.

In terms of ionic membrane currents and AP propagation, how do colder temperatures help alleviate the symptoms of Multiple sclerosis?

Temperature affects transmitter release mechanism; in colder temperatures will have a longer delay and less deterioration and symptoms

What is the 'delayed rectifier' and what is its role during an action potential?

The delayed rectifier is the voltage gated potassium channel; the delayed rectifier is responsible for the afterhyperpolarizing potential because these channels continue to open for a period that outlasts the action potential and the resulting increase in potassium conductance drives the membrane potential toward the potassium equilibrium potential.

What is the relationship between the length constant and diameter of an unmyelinated axon? What is the relationship between the length constant and diameter of a myelinated axon? What is the relationship between the length constant and spike conduction speed?

The greater the diameter of an axon (the lower the resistance) and graeater the radius and greater the length constant; myelin increases membrane resistance which increases the length constant big length constant = higher conduction speed

What properties make the neuronal membrane a good capacitor?

The heads of the phospholipids make the membrane good capacitor because it sets up the electrochemical gradient. Ion channels act like resistors because they are selective for specific ions and specific time "Leaky" capacitor because of the potassium leak channels

What do we mean when we say that the sodium channels underlie a positive feedback loop, and the potassium channels underlie a negative feedback loop?

The positive feedback loop is an increase of sodium conductance, leads to an inward current of sodium which depolarizes the cell and this loop continues with every action potential; depolarization causes an increase in K+ conductance, increasing the outward K+ current and causing repolarization that shuts off depolarization (negative feedback)

What is the evidence that the resting potential depends on the Na/K pump?

The resting membrane potential is kept at about -65mV. There has to be an unequal distribution of ions in order for the membrane potential to be steady at this value. The sodium potassium channel distributes 3 sodium out for every 2 potassium in to the cell to maintain the unequal distribution. Potassium permeability is so high that the resting should be closer to Ek but its not because of na/K

Define "reversal potential." What information can you get from knowing the reversal potential at a synapse?

The reversal potential is where inward current switches to outward current or vice versa. It is the equilibrium potential of an ion

Explain why the sodium currents first increase and then decrease as the command voltages become more and more positive in the Hodgkin - Huxley voltage clamp experiments (as in Fig. 7.3).

The sodium current first increases even though you would expect it to decrease because between -50mV and 10mV there is a marked increase in sodium conductance due to the activation of sodium gated ion channels which greatly outweighs the decrease in the driving force.

How do spiking neurons encode intensity of excitation?

The spike refers to an action potential; the frequency of action potentials can have an effect on the intensity of the action potentials due to the depolarization of the cell membrane.

How did Hodgkin and Huxley manage to sort out the sodium and potassium components of the membrane currents measured by the voltage clamp?

They found a way to block sodium channels by replacing most of the extracellular sodium with choline. By doing this, they were able to just look at potassium current when the sodium current was knocked out which was seen mostly during the falling phase

How do we know that there is more than one event required to open a potassium channel?

They open 1ms after Na channels do; they are delayed rectifiers, sodium must activate/ inactivate first (this is 2 different processes)

Briefly explain how transgenically labeled neurons and antibody labeled neurons are different. How are the two methods similar?

Transgenically labeled: fluorescent protein are incorporated into the genome and expressed in target neurons. Antibody labeled: antibody targeted to stain and stick to a certain protein. Both use proteins in order to target and fluoresce the targeted areas.

Relate each variable of Ohm's law to what it represents in a neuron.

V= voltage (membrane potential) I= current flow of ions R= membrane resistance

Both patch clamping and voltage clamping can record ion channel currents. What is the difference in scale between the two?

Voltage clamping hold the membrane at a certain potential to see how capacitance and current are affected All patch clamps can be voltage clamps but not all voltage clamps are patch clamps use patch to grab a single area of membrane

Given that they provide more information, why not always use intracellular electrodes to record neuronal activity in the brain?

You may not always want to use intracellular recordings because if you wanted to trace how different neurons communicate with one another you would want to look at a cluster of neurons. You would need a different recording strategy to look at the pathways of different neurons.

Where would you find each of the following: a) a stretch-activated channel? b) a voltage activated channel? c) a channel activated by an extracellular ligand?

a) stretch activated channel: skin or muscles b) voltage gated in neurons c) channel activated extracellular ligand: in neurons between pre and post synaptic cells

Where does the signal amplification come from in the increased calcium channel activity in cardiac muscle, caused by application of norepinephrine?

activates B-adrenergic receptors in cardiac muscle by norepinephrine which increases the rate and force of heart contraction which increase calcium which increases the action potential and contraction

What are 2 advantages that metabotropic synapses have over ionotropic synapses? What is one disadvantage of metabotropic synapses?

adjust efficiency of synaptic transmission they are slower

In a resting neuron, which ion, Na or K, is leaking faster across the membrane, or are their leakages equal

at rest, K+

Explain the reason that a spike in the Lateral Giant interneuron of a crayfish causes a larger EPSP in the Motor Giant, but not in the reverse condition (from the motor giant to the lateral giant), even though the two are connected by an electrical synapse.

because EPSPs don't go backwards; presynaptic won't get an AP

Glycine and GABA are common inhibitory neurotransmitters that result in the opening of anionic ionotropic receptors. Why do we only consider Cl- when we are talking about these receptors?

because its the only anion (will flow inward)

If ACh opens generalized cation channels, which let sodium in and potassium out, why is there a depolarizing psp?

because sodium conductance is higher

If the voltage change at the point of current injection into a dendrite is 10 mV, what is the voltage change one length constant away from that point?

bigger

Give an example of a synapse that shows a "direct" metabotropic action.

by subunit is freed and binds to ion channels to produce brief effects; GPCR

Synaptic facilitation and depression present opposite changes to the excitability of a synapse. Despite this, we can see the effect of both facilitation and depression at a synapse, how is this possible?

can increase quick then decrease over longer period of time

When studying the effect of PTP at the synapse of a chicken ganglion cell, experimenters hyperpolarize the membrane and applied the poison curare (a competitor for ACH receptors). Why did they do this and what did it allow them to see?

curare was used to reduce the amplitude of the EPSP. allowed them to see electrical coupling potential and a second slower depolarization is the EPSP produced by release of ACh from the presynaptic terminal

What is a gating current, and how is it measured?

current produced by movement of charge within a cell membrane, associated with the opening or closing of a channel aka asymmetry currents; Results of experiment where peak sodium current is plotted against the potential during the prepulse (voltage clamp experiments)

List 3 different techniques that allow targeted staining of neurons.

extracellular dye traces, transgenic cell labelling, and use of antibodies

What is the evidence that the threshold is higher for dendritic (calcium) spikes than for soma spikes?

figure 8.5 experiment... Moderate depolarization spread to soma where it initiates action potential then spread back to dendrite dendrite needed a larger depolarization to have an AP before the soma

Why do many neurons use action potentials, even though graded potentials can transmit more information per unit time?

graded potentials need to hit a certain level of depolarization to cause communication it can be information the cell doesn't need causing an excess

Write an equation for the potassium current leaving a neuron at resting potential.

iK = GK(Vm-Ek)

What effect would increasing membrane resistance have on the length constant and on the internal resistance of a neurite? What effect would increasing internal resistance have on the length constant and on the input resistance of a neurite?

increase membrane resistance increases length constant increasing internal resistance decreases the length constant

What's the difference between a metabotropic synapse and an ionotropic synapse?

ionotropic: used in direct chemical transmission, where neurotransmitter is released from a presynaptic ending binds to and opens ion channels metabotropic: use in indirect chemical transmission; interact with other membrane proteins to initiate sequence of steps leading to changes in ion channel activity or other metabolic processes

The Hodgkin-Huxley equations yield a whole family of equations that describe the time course of sodium and potassium conductances at different membrane voltages. What 2 specific variables in the equations change for the sodium conductance at different voltages?

max conductance of Na, time constant (m) and time constant (h)

List three advantages of electrical synapses over chemical synapses. Can you think of an advantage of chemical synapses over electrical ones?

more reliable (less likely to fail), faster, synchronized, and NO SYNAPTIC DELAY

Explain with an equation the way in which the time course of conductance can be calculated from the time course of current flow in a voltage clamp experiment.

needs answer

How could you tell if more than one sodium channel were in a patch recording?

needs answer

Explain why it is essential for much more neurotransmitter to be released at the neuromuscular junction (motor end plate) than at a synapse in the CNS.

neuromuscular junction is between motor nerve and a muscle fiber so it will need more neurotransmitter to get entire muscle to contract; An epp must exceed the spike threshold of a muscle fiber, but muscle fiber has low input resistance so more neurotransmitter is needed to produce a large epp

Multiple sclerosis is an autoimmune disease in which the immune system attacks oligodendrocytes, among other things. What is the most immediate effect of attacking oligodendrocytes? How will this affect the distribution of voltage gated sodium channels in the CNS?

oligodendrocytes make myelin, attacking them would make length constant smaller which makes conduction speed longer which is not good; less channels will be able to open

If the resting potential of a neuron is -70 mV and the chloride equilibrium potential is -65 mV, which way, in or out, will chloride ions flow through an open chloride channel?

out

If a patch of membrane containing a potassium channel is voltage clamped to -50 mV, which way, in or out, will potassium ions flow when the channel opens? In this case, would the current trace from the patch clamp amplifier go upward or downward during openings?

out and the current would be greater because the driving force is greater

When the membrane is depolarized to 0 mV, the time constant for the opening of m gates (tm)is about 0.2 ms and the time constant for n gates (tn) is about 1.5 ms. What does that translate to in terms of opening sodium versus potassium channels?

potassium channels are delayed in opening (delayed rectifiers); The potassium gates will open slower (delayed rectifier) than sodium channels Potassium is N and sodium is M; The membrane potential is closer to that of n gates so the driving force for the n gates is lower. WHen the driving force is lower, the activation of the gates will be slower.

Describe an experiment where you would test a synapse to see if it contains electrical or chemical synapses, or both. What feature of an EPSP allows us to differentiate between chemical and electrical synapses?

should have electrical coupling at beginning than chemical synapse because of synaptic delay

If a membrane transport protein in the neuron pumps chloride out of the cell, will this tend to make the resting membrane potential slightly more positive or more negative?

slightly more positive

Which has a greater internal resistance, a large neurite or a small one? How does this difference affect the change in voltage in response to injected current (or synaptic current)?

small neurite would need higher voltage or stronger current??

What ions carry the leakage current when the membrane is clamped to -85 mV?

sodium

Why is it incorrect to label NMDA receptors as metabotropic? What is the effect of NMDA receptors that might lead a person to think they are metabotropic?

they have secondary mechanisms but it is incorrect because the transmitter directly binds to NMDA bc its a receptor

What have patch recordings of sodium channels shown us about the pattern of channel openings that forms the basis for the sodium conductance curves? In other words, why is it wrong to say that sodium channels open quickly with depolarization?

they show us that there are Na-gated channels which creates an inward current when they are activated, however depolarizing repulses give smaller current responses because the driving force is lower; The sodium channels open at a certain membrane potential not just at any depolarization in the cell. When you have graded potentials, the cell can depolarize and not result in an action potential. The sodium channels open quickly when you reach a certain membrane potential.

For a synapse in which the postsynaptic channel is permeable only to sodium and potassium ions, what is true about the sodium and potassium currents at the reversal potential?

they switch direction at reversal potential

The reversal potential for a certain synapse has a reversal potential at -85 MV, suggesting that it is a potassium-mediated synapse. Would this be an excitatory or an inhibitory synapse? What could experimenters do to change the reversal potential at this synapse?

this would be an inhibitory synapse because it would force K+ to move out of the cell with its concentration gradient they can change reversal potential by changing the concentration of K+ inside the cell