Neurotic Physiology

First in our back to basics series, a very important topic indeed. Neurotransmission is at the basis of everything you read about MRI, neural circuitry, how areas of the brain communicate…basically a LOT of neuroscience requires that you know something about neurotransmission.

I suppose I thought for a while that if I was talking about dopamine and serotonin and GABA and things enough, people would just kind of “get” neurotransmission. And most people do. But it’s still a good thing to cover, partially because it’s kind of mind boggling to think about (well, Sci finds it mind-boggling), and partially because it helps you understand why changes in receptors, changes in transporters, or changes in release will have different effects. This comes in very handy when talking about various psychiatric and addictive drugs of which I am very fond. And so, your general post today: Neurotransmission.

And also, I get to DRAW!!! w00t.

The synapse. Do not be fooled by its commonplace appearance. Like so many things, it is not what is on the outside, but what is on the inside that counts. 🙂

So what are we looking at here? That blue bulbous portion that looks like a nose is the presynaptic neuron. The smiley below it in pink is the postsynaptic neuron. And neurotransmission is what gets a signal from one side to the other.

Now the presynaptic neuron has a signal. This stimulus is transmitted as an action potential eletrically down the neuron until it gets to the bulge in the picture, the synaptic buton.

But the electrical signal cannot just bounce on to the next neuron. There’s too much space in between the two neurons in the synaptic cleft. Instead, the stimulus of the action potential causes a rush of calcium ions into the synaptic buton, which bind to receptors on the inside.

This change in potential is going to affect little vesicles, little blobs of membrane inside the presynaptic neuron. These vesicles contain neurotransmitters, chemicals synthesized in the presynaptic cell, and stored in the vesicles until stimulated.

When the vesicles are stimulated by this influx of calcium caused by the approaching action potential, the vesicles begin to migrate to the cell membrane. Then, they can either merge with the membrane and release all their neurotransmitter into the synapse, or they can perform a “kiss and run” opening briefly at the membrane and only releasing a little of the neurotransmitter. It’s thought right now that the kiss and run is more common than dumping all the neurotransmitter in there.

So now the neurotransitting chemicals are in the synapse. They float across the tiny space in a random way, and in the process, bump into receptors on the other side.

Keep in mind, though. The neurotransmitters are not taken up by the receptors. Instead, they bind, and the receptor, which runs through the membrane in the postsynaptic cell, changes conformation on the inside of the cell, causing activation of pathways.

The receptors here are important. This is because there tend to be many different types of receptor for one type of neurotransmitter. For example, serotonin has 17 known receptors, and there might be more. The type of receptor on the postsynaptic neuron determines how the cell will react to the signal. This is a lot more refined than depending on neurotransmitter release. You can only change the AMOUNT of neurotransmitter released, not whether or not that neurotransmitter will be excitatory or inhibitory. That is left to the receptors. So depending on what the neurotransmitter hits, the result could be excitation or inhibition of the postsynaptic neuron’s action potential, or something even more complicated, like activation of specific gene pathways to produce specific proteins.

Not only that, receptor sensitivity to stimulation can change, either by changing the number of receptors at the postsynaptic membrane, or changing the sensitivity of the receptors that are there. There are lots of way to control how much and what kind of signals are getting across, and previous stimulations received will influence how the postsynaptic cell is capable of reacting later. These changes can be short-term or long-term, and can be responsible for starting processes like memory formation, learning, and addiction, as well as tons of other things.

A neurotransmitter is ONLY as good as its RECEPTOR!

So what happens then? You don’t want to leave the neurotransmitter sitting around in the synapse. Because it’s floating around at random, sitting in the synapse means it will continue to bump into receptors and pass signals on to the post-synaptic neuron. So the signal must be terminated. Depending on the neurotransmitter you’re dealing with (dopamine, serotonin, GABA, glutamate, acetylcholine, the list goes on), there are carious things that can happen. An enzyme can break down the neurotransmitter chemical into its component parts, or the presynaptic neuron can have transporters, which suck the neurotransmitter up back into the synaptic buton, either to be shoved back into vesicles, or to be degraded.

And the synapse clears out, vesicles fill up, calcium goes back out of the presynaptic neuron, and it’s all ready to begin again.

That’s a really, really basic picture of what’s going on at a synapse. But what, you may ask, is so mind-boggling about that? What boggles Sci’s mind is the tiny scale on which this is happening (the order of NANOmeters, which is 10 to the -9!!!), and the SPEED. This happens FAST. Every movement of your fingers requires THOUSANDS of these signals. Every new fact you learn requires thousands more. Heck, every word your are looking at, just the ACT of LOOKING and visual signals coming into your brain. Millions of signals, all over the brain, per second. And out of each tiny signal, tiny things change, and those tiny changes determine what patterns are encoded and what are not. Those patterns can determine something like what things you see are remembered or not. And so, those millions of tiny signals will determine how you do on your calculus test, whether you swerve your car away in time to miss the stop sign, and whether you eat that piece of cake.

If that’s not mind-boggling, what IS?!