There are two main ions involved in generating the action potential- Na+ and K+ (sodium and potassium, respectively). As I mentioned in the last post, there is more Na+ outside relative to inside and K+ has the reverse concentration gradient (meaning concentrations are different outside and inside- where for K+, it is greater inside the cell). There are three types of channels I will mention here- ligand-gated Na+ and voltage-gated Na+ and K+ channels.
The first thing that happens in an action potential is that Na+ (sodium) enters the neuron. It usually does so through ligand-gated Na+ channels, which is a fancy way of saying something- a ligand (often a neurotransmitter)- opens the channels and Na+ rushes into the cell.
Na+ is positive; therefore, it stands to reason that when Na+ enters, the cell would become more positive. When the cell is more positive, voltage-gated Na+ channels open. Voltage-gated (VG) simply means that when the positivity inside the cell reaches a certain level, they can open and let more sodium into the cell.
The cool thing about these channels is that you can see in the picture, they have a type of “ball” on a chain. This ball will swing in and close the pore after a little while, stopping sodium from entering the cell, even though it is still positive due to all the sodium inside the cell. We call this the “inactivated” state.
Voltage-gated K+ (potassium) channels will also open, but they are very slow. Slow to open and slow to close. When they finally open, the ball is closing the Na+ voltage-gated channels and K+ will rush outside the cell to make it more negative, or hyperpolarize, the neuron.
The action potential only travels one way down the axon because of the “ball” on the Na+ voltage-gated channels that prevent Na+ from entering again along that section of axon. Instead, the Na+ VG channels further down the axon will open and the signal will travel that way.
Recently, someone asked me to talk about Neurotransmitters, so I am going to go back to the basics as to how neurons work, what action potentials are, how they happen, and then what neurotransmitters are and what different ones may do!
Let’s begin to talk action potentials. Action potentials are how messages are carried from one neuron to the next. Neurons are specialised for this kind of signal because they have excitable membranes. This can be pretty hard to grasp, but essentially, they use specialized ion channels (things small molecules can move through) to send an electrical current down the length of the axon.
Action potentials are able to happen because the cell is kept more negative than the outside by having a larger amount of potassium (K+) inside the cell and larger amounts of sodium (Na+) outside the cell. This gradient, or difference in the concentrations inside and outside the cell, are created by the Na-K pump. These are like cell membrane club bouncers that push the K+ (hot girls) inside the cell (club) and push the Na+ (wasted people) outside the cell. If this analogy doesn’t work for you, then just try to get it from the basic science standpoint.
So you have the Na-K pump that keeps more K+ inside and more Na+ outside. To do this, it uses energy, known as ATP. Therefore, you might sometimes hear this referred to as a Na-K ATPase pump, simply meaning it uses ATP to work.
Apologies for the radio silence as of late. I’ve been finishing up my thesis, which I will defend this week (and then hopefully have my official doctorate)! It’s been a lot of work, so I haven’t had time/energy to work on posts, but hopefully starting next week or the week after, I should be back to the usual frequency! Please bear with me! In the meantime, here are some lovely neurons!! Enjoy!
[Image Source: Dr Jonathan Clarke. Wellcome Images]
This is a hippocampal neuron (read about hippocampus here) infected with GFP and DsRed ( the green+red combination is why it looks kind of orangey). You can really see all the different branches the dendrites have made to receive input from other neurons. Besides which, it looks absolutely stunning!
There are twelve nerves that come out of or into the brain (the rest of the nerves go out of and into the spinal cord). These cranial nerves have been whitened on this picture, and you can see all twelve pretty well (one of each on each side). They include the olfactory for smelling (the most anterior- or on this picture, the highest), optic for seeing (the second highest, shown as they cross at the optic chiasm), as well as many motor and sensory neurons for the face- and the vagus, which you may have heard of in terms of heartrate, breathing, etc. (The vagus modulates the parasympathetic response- or the relaxing as it is opposite to the stress response. The vagus slows heartrate, decreases breathing, relaxes muscles, decreases sweat production, increases digestion, etc.)
There are many mnemonics for remembering the twelve in order (I is the most anterior to XII being the most posterior- or top to bottom on this image). They can be named by their number (for instance, the olfactory nerve is also cranial nerve I and the vagus nerve is also CN X) or by their more common name. The mnemonic I was taught to learn the twelve was: “On Old Olympus’ Towering Top, A Friendly Viking Grew Vines and Hops” but I will fully admit it never worked well for me. (This sentence corresponds to the first letter of each nerve: olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, accessory, hypoglossal.)
The nerves carry motor information (movement), sensory information (touch/taste/smell/vision), or both motor and sensory information! There are also many mnemonics to remember which nerve carries which kind of information. The one I was taught is “Some Say Marry Money, But My Brother Says Bad Business Marry Money.” S means sensory, M means motor, and B means both, starting with the first word corresponding to the first nerve through the last corresponding to the twelfth nerve (so, for instance, ofactory and optic, the first two nerves are both Sensory, the next two- oculomotor and trochlear- are Motor, etc).
Basic anatomy- FLASHBACK
This is a coronal slice through the brain (coronal slices are like bread slices- if you think about your head being a loaf of bread, how would you slice it?). You can see that there is a darker layer all around the outside and the inside is lighter in color. The darker stuff is the gray matter, and this is where all the neuronal cell bodies are. This is the critical part that we refer to as “cortex”- as you can see, it’s pretty small in comparison to the whole brain- only a few millimeters thick in most places. The inner stuff that’s lighter in color is the white matter, and is made up of axons coming down from cortex to the rest of the body (or to other parts of cortex). It’s lighter in color because all these axons are myelinated, and myelin is white.
The holes in the middle of the brain are the ventricles. These are spaces that are normally filled with cerebrospinal fluid (CSF). CSF turns over almost constantly (lots is being produced throughout the day and it is recycled out through the bloodstream). CSF is largely thought to be protective- the fluid keeps the brain from rubbing against the skull or hitting it too hard when you move or have a jolt. However, it also can help with chemical exchange or cleanup (such as of neuroendocrines- neural hormones) and keeping blood flowing into the brain.
FLASHBACK- Alzheimer’s Brain
Alzheimer’s disease is characterized by neurodegeneration (death of neurons) and the appearance of amyloid beta plaques and tau neurofibrillary tangles thought to cause the neurodegeneration (for more info, go here). This leads to a variety of cognitive problems- perhaps the most well known is memory loss, but there is also severe cognitive decline (inability to do simple tasks, such as draw a straight line, connect the dots, etc.).
This side by side comparison of an Alzheimer’s brain with a healthy brain really helps to illustrate the severe neurodegeneration that occurs. The ventricles seem to become bigger (due to loss of the brain tissue that would normally surround them), gray matter decreases a lot- the cell bodies of neurons are dying, and this is what really causes the cognitive decline- for motor tasks, simple thinking tasks, etc. You can really see how much of the gray matter has disappeared in the above image. Additionally, the hippocampus (read more about hippocampus here) is almost entirely dead and gone. The hippocampus is that squiggly thing on the bottom center (on the inside of the section that loops down on the side) that is a hole in the Alzheimer’s brain. You can see how it kind of resembles the rodent hippocampus in the linked post above. Hippocampus, which is responsible for memory storage, creation, and some retrieval, really cannot work well when it has degenerated in Alzheimer’s, and it is one of the first places to experience degeneration, which is why memory loss is one of the first symptoms.
FLASHBACK How do we feel cold or heat? (question by brokenglass)
There are special temperature sensing channels called TRP channels (TRP stands for transient receptor potential, but you won’t see that much). TRP channels were first isolated in Drosophila (fruit flies) and responded to light. Now we know that some TRP channels actually respond to narrow ranges of temperatures (see figure above with responses of different TRP channels spanned across degrees centigrade) and are found in many organisms, including humans (mostly of the TRPV varieties, though TRPM8 and TRPA1 also seem to be important in humans). Essentially, when exposed to a temperature in their range, TRP channels open and let ions into the neuron, depolarizing it, causing an action potential and sending signals to the brain. This is a much more complicated process (as all signaling in neurons actually is) with changes occurring inside the cell due to their activation, but that is the general idea.
Some of these TRP channels are located on C-fibers (unmyelinated neurons that generally conduct pain signals) and that is why extreme hot or extreme cold can feel rather painful. TRP channels can also be activated by chemicals, as I talked about last week.
Ask me your own questions!
Balance is regulated by the vestibular system, which mostly consists of the semicircular canals inside your ear. The semicircular canals have hair cells (these are cells that look like they have a mohawk- the mohawk is composed of stereocilia, which are thin protrusions that look like hairs- these hairs are shown in the image above). The stereocilia have a layer of otolith, or little calcium deposits, on top of their tips. When your head moves to the side, the otolith shift and pull the stereocilia in one way or another. Depending on the way the stereocilia move, your brain can figure out where your head is in space and help you maintain balance.
When someone drinks alcohol (whether you have experienced this first hand or merely seen it on TV), they lose their balance. This is caused by the increase of alcohol (ethanol) in the blood and fluids of the body- including in the semicircular canals of your ears. Essentially, this causes the stereocilia to become floppy and prevents them from accurately moving with the otolith; thus, you have a loss of balance. This also causes the vertigo (dizziness) you might feel when you lay down after drinking (if you put your foot out of bed and set it on the floor, this should help your body orient and make you a little less dizzy).
How can things taste or feel “cold” or “hot”? FLASHBACK
This sensation is called chemosthesis and refers to the fact that chemicals that you can taste or apply to your skin can cause “touch” feelings (temperature is part of the “touch” sense whereas chemical sensing is either “taste” or “smell” typically). This would be with icy hot where it feels cold or hot, but your skin temperature does not actually change or when you eat mints and they “taste cold” or when you eat some spicy food and it “tastes hot”.
These cold or hot feelings or tastes are not actually related to temperature. Two chemicals in particular can activate the TRP channels we talked about previously. Menthol (found in mint and icy hot) activates TRPM8 channels that typically sense cold temperatures, while capsaicin (found in chili peppers and other “spicy” foods) activates TRPV1 channels that typically respond to heat. These chemicals attach to the TRP channel and cause it to open the same way temperature would, causing the same responses in the neurons- in your mouth and on your skin. This is why the foods or other chemicals containing these compounds really do taste or feel “hot” or “cold”. It is the same neural response.
Coincidentally, this is why drinking water after having some spicy foods will not help- the water will just move the chemicals around and cause them to activate even more TRP channels, making the feeling stronger. Most concentrated fluids, like milk, can help wash away and displace the chemicals, so the TRP channels will stop being activated.
DO WE HAVE FREE WILL?
Had a great #NeuroLoveChat last night on my twitter (@NeuroLoveBlog). Thanks a bunch to the people who participated! I really enjoyed speaking with all of you.
One of the many interesting questions posed was asked by @zfield27: “What is your stance on the free will vs. no free will argument (if you have one)?”
This is actually a pretty fascinating and loaded debate. Quite honestly, I don’t think it’s something easy to design an experiment to conclusively prove or disprove (perhaps because it would be to our psychological detriment to disprove it), and thus, we might never have a “real” answer.
On the one hand, evidence has been growing that free will might be an illusion. For instance, Hallet (2007) found that the volitional control of movement was an illusion- volitional control meaning, for instance, you decide to move your arm, and then you do. Neurons in the brain had already decided that the arm was going to move before the conscious was on board. Other studies have found similar things- that the conscious gets on board after the “decision” has been made by the brain (Soon et al., 2008).
This is not to say that free will does not exist. I myself would love to believe in free will, but I don’t know if it is that belief that clouds a reasoned consideration of its existence. It’s clear that most people believe in free will, and it appears that a belief in free will is necessary for one’s psychological well being (Leotti, Iyengar, & Ochsner, 2010). So then, is it worth breaking the illusion of free will (if it is an illusion) to keep searching for an answer?
If you did want to prove free will, how would you do so conclusively? I think that would be an incredibly difficult question to address. I wanted to lay out argument for you here though, because I think it is absolutely fascinating to consider.
[Image Source; also thanks to @zfield27 for the question!]
Don’t forget!! TONIGHT, 8-10pm Eastern Time, I’ll be taking/answering any questions you might have with the hashtag #NeuroLoveChat on my twitter, @NeuroLoveBlog. Feel free to submit questions beforehand, if you won’t be able to make it, and I will try to answer them all. You are also welcome just to drop in to say hi!
Thanks so much for following, and I hope to chat with some of you tonight!
As promised, I am planning another live chat with a couple days advance notice! This will be Wednesday, December 19, 2012 from 8:00 pm to 10:00 pm Eastern Time! If you don’t already, follow me on twitter @NeuroLoveBlog. I’ll be following the tag #NeuroLoveChat so I can see any questions you ask and will reply using that tag if you want to follow along too! Any questions you’ve got about applications, neuroscience, etc would be happily received and I will answer as many as I can in that two hour window! You can send me questions in advance on twitter if you can’t make it or through the ask feature on here (just tag them #NeuroLoveChat so I will know what they are for). If you want to ask anonymously, you can send questions through the ask feature on tumblr! If I get some good/common questions or questions that take a while to answer, I might post them with my replies on here Thursday! We’ll see how it goes, but I want to make sure I answer any burning questions that you may have! I hope to see many of you on Wednesday!!
Just some neurons!