Signal Transmission

## Overview

There are four stages to convey a signal from one neuron to the next:

1. **Reception**: receiving input from other cells (or sensory stimuli) via dendrites
2. **Integration**: summation of inputs
3. **Conduction**: if threshold is reached, an action potential brings the signal from one side of the cell to the other.
4. **Transmission**: neurotransmitters go from the presynaptic cell to the postsynaptic cell to pass the signal along.

The rest are details that carry out this process.

 How to Learn About Resting Potential and Action Potential

Everyone learns differently, but I think any neuroscience student would tell you that it took him/her many re-readings and re-watchings to understand the action potential. There is a basic process that skips a few details but will give you the foundational logic, and Khanacademy does a great job teaching this. Here is what I recommend:

1. Start with Khanacademy before you learn about action potentials in a real course, since courses will go much more in depth. It has videos that are a good starting point for understanding neural transmission. Especially important is the "Correction to sodium and potassium pump video" , since it pinpoints exactly how the membrane's permeability plays a role in setting up the concentration gradient. The 3:2 ratio is deceptive; this particular ratio isn't the primary cause of either the concentration or electrical differences (i.e. the pump would be just as effective with a 1:1 ratio). The real cause of the membrane potential is the high permeability to K+ (potassium leak channels) and low permeability to Na+ and the fact that the ions are each (mostly) restricted to one side of the membrane. Carefully read the yellow text in the thumbnail of the video to ensure that you understand this. You may have to watch these videos multiple times; make sure you internalize the basics before you move on.
2. Strangely enough, one of the best textbook explanations I have found of the nuances of the action potential is in the Cognitive Neuroscience textbook that JHU recommends. The textbook is completely unnecessary for the course, so simply get it from reserve at the library for a couple of hours. Once you understand the basic process from Khanacademy, you can start understanding the details. I also recommend that you do this step before you learn about it in a course.
3. Finally, take your course and read and re-read everything your instructor gives you.

### Confusing Bits

I have by no means interviewed every single neuroscience major, but there are some parts of the resting potential/action potential process that I noticed many people found confusing (including me). Once you've done all the above steps, it might be helpful to read this.

#### **What is the purpose of all these pumps, channels, and transporters?**

So you've read about all the pumps and channels and you've memorized what each of them does individually and what ions go through which. But what's the point? Why do you *want* this ion to go here or there? Here's the big picture:

* **The leak channels are to create the membrane potential difference.** The sodium-potassium pump has put a lot of sodium outside the cell and potassium inside the cell, but that only gives you a concentration difference of these ions across the membrane. Even though you have a lot of sodium outside and a lot of potassium inside, those are both positive ions. Who's to say that they don't cancel each other out? A lot of positives outside and a lot of positives inside leaves you with no difference between the *charge* of the inside and outside, even if the positives are from ions with different names. That's what the potassium leak channels are for. Since it's positively charged, there will be more positive charge outside the cell than inside when it leaks out. The inside will be left with the negatively charged organic ions (DNA, RNA, etc.) that were there to begin with, so you'll have a net negative charge inside.
* **The sodium-potassium pump is to maintain the concentration difference of sodium and potassium.** The above step with the leak channels only works because there was more potassium inside the cell than out. Channels only let ions go from high concentration to low, so if potassium is diffusing *out* of the cell, that means there had to have been more potassium *inside* the cell to begin with. But if we let the leaking continue long enough, eventually there won't be enough potassium inside the cell for it to want to come out\*. So there needs to be a device to put the potassium back inside the cell so that it keeps "wanting" to come out. This device is the sodium-potassium pump. The next bullet explains why we want sodium to build up outside of the cell.

\*The next sentence you'd expect there would be "It would diffuse out until there were equal potassium concentrations inside and outside of the cell," but this isn't really the case. The negative charge inside the cell would cause some positively charged potassium to stay in, so there would still be a slight concentration difference of potassium. But it would still be "happy" staying in, since it's cancelling out the negative charge inside. There needs to be so much potassium inside that its "desire" to leave all the other potassium ions outweighs its "desire" to stay inside and balance the negative charges. Something inside you should now be screaming that the "desires" of ions are not on the same planet as empirical measurements, but don't worry--the Nernst equation quantifies all this.

* **The sodium buildup outside the cell does two things: facilitates EPSPs, and powers secondary transporters (which then facilitate IPSPs and calcium ion influx).** The sodium-potassium pump pushes potassium into the cell, which we just saw the use for. But why would we want sodium to be outside the cell? If the sodium is outside the cell and wants to come in, then:
	+ when an excitatory neurotransmitter binds to a ligand-gated sodium channel, the sodium will rush in (causing an EPSP because sodium ions are positively charged). If you didn't have all that sodium outside the cell, it wouldn't rush in.
	+ it diffusing down its concentration gradient will release energy. It's going from high potential energy to low potential energy, just like water from the top of a waterfall when it flows down. You could use that energy to power a water wheel. Similarly, neurons use the energy of sodium going from high potential energy to low potential energy (by it going from high concentration to low) to power the reverse process for chloride ions. There is a higher concentration of chloride outside the cell, so chloride ions don't want to come out. But what if there was a device that used the energy of sodium diffusing down its concentration gradient to power chloride going against its concentration gradient? That device is called a secondary transporter, and it does exactly that (there is also one for sodium and calcium ions). Why would we want a higher concentration of chloride outside the cell than inside? Similarly to how sodium influx causes an EPSP, chloride influx will cause an IPSP since chloride ions are negatively charged. This will only work if there is a lot of chloride outside the cell.
* **Basically, the sodium-potassium pump and secondary transporters maintain the concentration difference across the membrane, while the potassium leak channels maintain the voltage difference across the membrane.**