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Principles Neuro MT1
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61
Physiology
Undergraduate 3
09/23/2009

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Term
cognitive neuroscience
Definition
Tries to understand performance of the human brain
Term
Circuit Neuroscience
Definition
tries to find out how circuits depend on properties of neurons and synapses
Term
molecular/cellular Neuro
Definition
studies individual or groups of molecules, biochemistry of ways brain cells work
Term
pumps
Definition
Move ions and molecules across membranes
Term
Channelopathies
Definition
disease resulting from mutations in genes encoding channels, such as Hyperkalemic Periodic Paralysis, which is a mutant in SCN4A (skeletal sodium channels)
Term
Patch clamp
Definition
refined form of voltage clamp. pressed against a small area of the cell to form a gigaohm seal. resistance allows it to electronically isolate the currents across the membrane patch with little noise.
Term
voltage clamp
Definition
a type of clamp that sets a voltage, and monitors the amount of current required to stay at that voltage. used often, especially when not looking at the capacitive current...
Term
current clamp
Definition
a type of clamp that sets a current, and then monitors the change in voltage. Used especially when viewing AP spikes.
Term
Ohm's Law (equation)
Definition
V = IR, and R = 1/G
Term
Nernst Equation (simplified)
Definition
Ex = (-58/z) log(Conc(x)[in])/(Conc(x)[out]))
Term
Goldman equivalent circuit equation
Definition
Vm = ExGx + EyGy.../Gx + Gy...

Remember to convert ALL units to standard.
Term
current of an ion in relation to driving force
Definition
i(ion) = g(ion) * (Vm - E(ion))
Term
permability
Definition
depending on the structure of channels, independent of concentration of ions. Physical measure of how easily a cell lets ions in.
Term
conductance
Definition
changes with the permeability of ion channels. electrical term..
Term
Membrane time constant (tau) (formula, explanation)
Definition
T = RC | how quickly the membrane comes to steady state depend
Term
Time for a cell to change a certain membrane potential (formula)
Definition
Delta V = I * R(m) * (1-e^(-t/tau))

or!

Vm = VRest + IR(1-e^(-t/tau))
Term
Prove that the early inward current found at 0.5 ms in an AP is sodium (more than the fact that the x-intercept is at +50, which is Ena+)
Definition
A good way to provide even more definitive proof is to first map an IV curve in voltage clamp of the cell with its normal concentrations. We should expect to see Sodium intersecting the x-axis at its equilibrium point, +50 mV. Then, we can take another recording after shifting the extracellular concentration of sodium (since the channels will be open around this voltage anyway). We can use the Nernst equation to calculate the new equilibrium point. If the new graph's x-intercept is at the new equilibrium point after changing the sodium concentration, this is good proof that Sodium is responsible for the early inward current.
Term
Prove that K+ is responsible for the late outward current
Definition
The best way to do this involves the tail currents, because the K+ channels we are trying to measure are actually closed at -80mV (Ek), we need to open them before we can determine whether or not K+ is the ion responsible for the current. To do so, we can quickly pulse the cell up to +20 mV. this will open the K+ channels. Then, we return the cell to -80 mV (or even hyperpolarize it further, since at -80 it would be flat and it will be easier to see the intercept). The channels will close slowly, so we will have time to measure the current required. The current should go flat at this point on our IV curve, since Ek = -80. Then, we can repeat this process after shifting the extracellular concentration of K+, and recalculating Ek. If the x-intercept is now at the new Ek, this is good evidence that K+ is indeed responsible for the late outward current in an AP.
Term
TTX (tetradotoxin)
Definition
Used to block Na+ channels. Good for focusing on the K+ current when looking at basic APs.
Term
TEA - tetraethalamonium
Definition
Blocks K+ channels. Good for focusing on Na+ current when looking at basic APs.
Term
absolute refractory period
Definition
ARP - defined as the time after an AP a neuron can't fire an AP. This is because of the inactivation of sodium channels. They need to be hyperpolarized to be de-inactivated. Also, however, there is a certain amount of time it takes to REMOVE the activation, so time of recovery is important.
Term
relative refractory period
Definition
HARDER to fire an AP because the cell is in a hyper-polarized state. Will take MORE current to fire an AP, but still possible.
Term
Experiment to measure how long it takes sodium channels to recover from inactivation
Definition
Put the cell in V Clamp (to avoid problems with the capacitive current). Next, put the cell in TEA to ignore the delayed rectifier K+ current. Then, activate the Na+ Current (and an AP), bring back down to a lower voltage, and then measure the time between succeeded depolarizations.
Term
Configuration of sodium channel
Definition
The alpha subunit of the sodium channel has 4 similar ('repeat') domains consisting of 6 trans-membrane segments each. The voltage sensitivity is caused by one of the trans-membrane segments in each domain being sensitive to voltage and moving in response to voltage change. This movement causes a slight change in the shape (conformation) of the protein. This conformational change causes the pore in the center of the protein to open or close. Also there is the loop between the 3rd and 4th domains that blocks the channel causing the it to become inactivated.
Term
Brain and spinal cord Na+ Genes:
Definition
SCN1A
SCN2A
SCN3A
SCN8A
Term
Skeletal muscle Na+ gene
Definition
SCN4A
Term
cardiac muscle Na+ channel gene, heart + uterus gene, and glial gene
Definition
SCN5A, SCN6A, SCN7A
Term
myotonia
Definition
Muscle is TOO excited...many action potentials. Seen sometimes in HPP
Term
HyperPP
Definition
autosomal dominant disorder that is heterogyzgous, mutation in SCN4A. Na+ channels have trouble inactivating, causing Myotonia sometimes when cells aren't depolarizing enough (trouble with muscle tensing..) because of the decreased rate of hyperpolarization (with Na+ channels not inactivating). Also can cause PARALYSIS episodes when increasing levels of potassium. If you increase extracellular potassium, you're depolarizing the cell even FURTHER, meaning the cell cannot hyperpolarize. The wild type channels (since there are some) don't have time to hyperpolarize...need longer periods of time to truly reset it.
Term
why current decreases over time in passive propgation (besides resistance)
Definition
current is leaking out of channels as it goes down an axon! Capacitance ALSO slows it down and takes current. Delta v decreases. Axial resistance along cytoplasm, too
Term
R(a)
Definition
Axial resistance along cytoplasm. Proportional to the diameter of the cell such that Ra is proportional to 1/r^2
Term
Equation for finding the distance a current will travel (Vx), where V(0) is the starting point. Equation for lambda.
Definition
Vx = V(0)e^(-x/lambda)
Lambda = sqrt(R(m)/R(a))
Term
electrotonic potential
Definition
detrimental potential? how far a neuron's influence spreads down an axon..
Term
Nodes of Ranvier
Definition
Spaces in between myelin sheath segments full of Na+ channels for AP propogation.
Term
Myelin is composed of (and by):
Definition
Specific proteins and connexons that allow nutrients to cross the sheath. It increases Rm dramatically and decreases Cm dramatically (by the thickness of the sheath). Myelin is made by oligodendrocytes in CNS and Schwann cells in PNS.
Term
Myelin increases the speed of the AP in what two ways?
Definition
- Capacitance is gone, so this increase the rate of depolarization in the individual neurons...small nodes charge quickly
- Increase lambda dramatically, which speeds up propogation
Term
challenges with myelin spacing
Definition
You need the nodes to be close enough together so that the AP doesn't fail, but long enough that it speeds up the AP.
Term
What will happen if you kill myelin? How could one hypothetically fix this functionally?
Definition
APs are likely to fail to propgate since lambda is dramatically decreased, and the sodium channels are so far spread apart. To try and fix this, you either need to create more Na+ channels in the membrane (allowing SOME recovery of function, since the APs will propgate much slower), or you can remyelinate.
Term
Astrocytes function?
Definition
Provide support in the Blood brain barrier, deliver nutrients to cells
Term
Difference between peripheral and central myelin?
Definition
Peripheral main protein is P0, which allows myelin sheaths to be tightly packed, providing some protection from damage.
In CNS, concerned more with space, so this protection is not required.
Term
What kind of disorder is Multiple Sclerosis, and how did we discover it?
Definition
MS is an autoimmune disorder in which the bodies antibodies attack the myelin. We discovered it was an autoimmune disorder by injecting myelin basic protein into mice, and noticing how it affected their bodies similarly. Put us on the right track.
Term
MS basic etiology
Definition
starts in early 20s, more common in women, generally in colder climates. Generally show visual problems, peripheral weakness.
Term
I(a)
Definition
transitory K+ current. Quickly activated and inactivated, and believed to be important in the rate of action potential generation, particularly at lower frequencies.
Term
How can we detect MS?
Definition
- MRI brain and spinal cord, look for lesions (in white matter)
- functionally, can look at peripheral conduction velocity of neurons.
- also can look for a visual problem using evoked potentials and see if there is a slower reaction than the visual cortex than in normal people
- biopsy
Term
Current way to treat MS
Definition
- Interferon, which supresses immune system
Term
basic types of neurons/ion channels (for example, tonically active) and what they look like...
Definition
A) Silent neurons - flat..
B) tonically active - normal trains of spikes.
C) Bursters - bursts of APs, then rest (like thalamic neurons)
D) Plateau Neuron - state based neurons that are firing when "on", and silent when "off". Used in Short Term Memory.
E) Post Inhibitory Rebound - neurons that get more excited after inhibition then before
Term
Delayed rectifiers (I(k))
Definition
turns on after the depolarization of an AP, providing an outward potassium current that helps hyperpolarize the cell. TEA sensitive.
Term
Calcium channel composition/example ions that can block it
Definition
Composed of 5 subunits. Can be blocked by Co++, Mn++, Cd++
Term
High threshold calcium/L-channel
Definition
pretty much always an inward current (meaning it will help depolarize the cell). Long lasting, persistant depolarizing currents. Can be blocked by drugs selectively.
Term
T-type calcium channels
Definition
Transitory. Time and voltage dependent activation. Channels need to be hyperpolarized to de-inactivated and show inward current again after the spike.
Term
Example experiment to distinguish between I(a), I(k), and calcium-activated potassium current after changing from -80 mV to +20 mV (NOTE: THIS EXPLANATION IS MY ATTEMPTED ANSWER AND COULD BE WRONG)
Definition
First task is to find effect of calcium activated K+ current. The easiest way to do this is to first find the measure of all three currents combined. Then, block Ca+ channels with an ion like Mn++ or Co++, and look at your potassium currents over time. Then, subtract this from the original to get a difference current representing the Calcium-dependent K+ current. Next, we need to find a difference current between I(k) and I(a). To do so, we can hold the cell at -40 mV for a while, and then pulse to +20 to open the I(a) channels. When back at -40, they will inactivate while the delayed rectifiers work to hyperpolarize the cell. We now have the delayed rectifier current graph. Now, simply subtract that from the graph without the Ca+-activated K+ current to get the I(a) graph.
Term
Ca++ activated potassium channels
Definition
Require binding of Ca++ to open the channel. Can open with voltage, but usually require a strong Ca++ current to open. This will help hyperpolarize the cell
Term
K+ inward rectifiers
Definition
Function to regulate the cell's threshold and membrane potential. Tend to act when the cell is NOT depolarized, and keep cell at lower voltages. Open pore can be blocked by Mg++ and polyamines.
Term
I(h)
Definition
Hyperpolarization-activated inward current (sag potential). Allows Na+ and K+ through. It is opened by hyperpolarization, and provides a slow inward current into the cell. Acts to slowly depolarize a cell that is hyperpolarized.
Term
Describe the thalamic burster cell, all the currents involved, and how they create the bursting effect (I feel like this will be an essay, or something close. She spent half a class on it)
Definition
(draw the burster cell, label the steps that she did on the board)
Going into Step A, the cell is being hyperpolarized. This will deactivate the delayed rectifier, the calcium activated K+ current, the transitory sodium current, and the low threshold Ca++ current.
Going into B, I(h) has been activated, which will start to depolarize the cell again. This will activate the low threshold Ca++ current.
Going into C, the Ca++ current is depolarizing the cell and building up calcium within it. Eventually, it will depolarize the cell to threshold, activating both the transitory, fast sodium current (causing the spike) and the delayed rectifer (which will help repolarize after the spikes).
Going into D, we see a burst because the continuous influx of Ca++ from the low threshold calcium current keeps the cell depolarized (it is working against the delayed rectifier). However, as we approach D, the Ca++ level has risen enough to activate the Ca++-activated K+ channel, which hyperpolarizes the cell (and counterbalances the Ca++ low threshold current) and pumps out Ca++, which starts to turn off the low threshold Ca++ current. The cell is hyperpolarized, and we go back to A.
Term
The period of burst depends on the interaction of...
Definition
The channels. Using this principle we can create oscillators for the brain.
Term
Phase response curve
Definition
used to describe how oscillators...well...oscillate.
Term
How do you create a phase delay?
Definition
Hyperpolarize the cell right before a spike. This will delay the spike, and all succeededing spikes becasue of the delay in the first. This is a phase delay.
Term
How do you make a phase advanace?
Definition
Hyperpolarize the cell mid-burst. This will advance the next and all other bursts.
Term
Entrainment
Definition
Neurons oscillation cycles can be entrained to external stimuli, like light, or to that of other neurons as such that we cannot stablely change them and create phase delays and advances by hyperpolarizaiton of them
Term
How would you be able to tell if a neuron in the brain is being controlled by itself or another neuron?
Definition
Try to phase advance or delay it. If you cannot stablely entrain it to your electrode, it is probably being entrained by another neuron.
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