When we pay careful attention, there are two neurochemicals, neuromodulators as they're called, that are released from multiple sites in our brain that highlight the neural circuits that stand a chance of changing. Now, it's not necessarily the case that they're going to change, but it's the first gate that has to open in order for change to occur.

And the first neurochemical is epinephrine, also adrenaline. We call it adrenaline when it's released from the adrenal glands above our kidneys. That's in the body. We call it epinephrine in the brain, but they are chemically identical substances. Epinephrine is released from a region in the brainstem called locus coeruleus.

Fancy name, you don't need to know it unless you want to. Locus coeruleus sends out these little wires we call axons such that it hoses the entire brain, essentially, in this neurochemical epinephrine. Now, it's not always hosing the brain with epinephrine. It's only when we are in high states of alertness that this epinephrine is released.

But the way this circuit is designed, it's very nonspecific. It's essentially waking up the entire brain. And that's because the way that epinephrine works by binding particular receptors is to increase the likelihood that neurons will be active. So no alertness, no neuroplasticity. However, alertness alone is not sufficient. As we would say, it's necessary, but not sufficient for neuroplasticity.

We know this is true also from the work of Hubel and Wiesel where they looked at brain plasticity in response to certain experiences in subjects that were either awake or asleep. And I hate to break it to you, but you cannot just simply listen to things in your sleep and learn those materials.

Later, I'll talk about how you can do certain things in your sleep that you're unaware of that can enhance learning of things that you were aware of while you were awake. But that is not the same as just listening to some music or listening to a tape while you sleep and expecting it to sink in, so to speak.

Epinephrine is released when we pay attention and when we are alert. But the most important thing for getting plasticity is that there'll be epinephrine, which equates to alertness, plus the release of this neuromodulator acetylcholine. Now, acetylcholine is released from two sites in the brain. One is also in the brainstem and it's named different things in different animals, but in humans, the most rich site of acetylcholine neurons or neurons that make acetylcholine is the parabigeminal nucleus or the parabrachial region.

There are a number of different names of these aggregates of neurons. You don't need to know the names. All you need to know is that you have an area in your brainstem and that area sends wires, these axons up into the area of the brain that filters sensory input.

So we have this area of the brain called the thalamus and it is getting bombarded with all sorts of sensory input all the time. Costello's snoring off to my right, the lights that are in the room, the presence of my computer to my left, all of that is coming in.

But when I pay attention to something, like if I really hone in on Costello's snoring, I create a cone of attention and what that cone of attention reflects is that acetylcholine is now amplifying the signal of sounds that Costello is making with his snoring and essentially making that signal greater than all the signal around it.

What we call signal to noise goes up. So those of you with an engineering background will be familiar with signal to noise. Those of you who do not have an engineering background, don't worry about it. All it means is that one particular shout in the crowd comes through, Costello's snoring becomes more salient, more apparent relative to everything else going on.

Acetylcholine acts as a spotlight, but epinephrine for alertness, acetylcholine spotlighting these inputs. Those two things alone are not enough to get plasticity. There needs to be this third component. And the third component is acetylcholine released from an area of the forebrain called nucleus basalis. If you really want to get technical, it's called nucleus basalis of my nert.

For any of you that are budding physicians or going to medical school, you should know that. If you have acetylcholine released from the brainstem, acetylcholine released from nucleus basalis and epinephrine, you can change your brain. And I can say that with confidence because Merzenich and Reckin's own, as well as other members of the Merzenich lab, Michael Kilgard and others, did these incredible experiments where they stimulated the release of acetylcholine from nucleus basalis, either with an electrode or with some other methods that we'll talk about.

And what they found was, when you stimulate these three brain regions, locus coeruleus, the brainstem source of acetylcholine, and then the basal forebrain source of acetylcholine, when you have those three things, whatever you happen to be listening to, doing or paying attention to, immediately in one trial takes over the representation of a particular area of the brain.

You essentially get rapid, massive learning in one shot. And this has been shown again and again and again in a variety of papers, also by a guy named Norm Weinberger from UC Irvine. And it is now considered a fundamental principle of how the nervous system works. So while Hubel and Wiesel talked about critical periods in developmental plasticity, it's very clear from the work of Merzenich and Weinberger and others, that if you get these three things, if you can access these three things of epinephrine, acetylcholine from these two sources, not only will the nervous system change, it has to change.

It absolutely will change. And that is the most important thing for people to understand if they want to change their brain. You cannot just passively experience things. And repetition can be important, but the way to use repetition to change your brain is fundamentally different. So now let's talk about how we would translate all the scientific information and history into some protocols that you can actually apply, because I think that's what many of you are interested in, and I'm willing to bet that most of you are not interested in lowering electrodes into your nucleus basalis, and frankly, neither am I.

So I'm not going to tell you what to do or what to take. I'm going to describe what the literature tells us and suggests about ways to access plasticity. We know we need epinephrine, that means alertness. Most people accomplish this through a cup of coffee and a good night's sleep.

So I will say, you should master your sleep schedule, and you should figure out how much sleep you need in order to achieve alertness when you sit down to learn. All the tools and more science than probably you ever wanted to hear about sleep and how to get better at sleeping and timing your sleep, et cetera, and naps, and all of that is in episodes two, three, four, and five of the "Huberman Lab" podcast.

So I encourage you to refer to those if your sleep is not where you would like it to be. Your ability to engage in deliberate focused alertness is in direct proportion to how well you are sleeping on a regular basis. I think that's kind of an obvious one. So get your sleep handled.

But once that's in place, the question then is, how do I access this alertness? Well, there are a number of ways. Some people use some pretty elaborate psychological gymnastics. They will tell people that they're going to do something and create some accountability. That could be really good. Or they'll post a picture of themselves online and they'll commit to losing a certain amount of weight or something like this.

So they can use either shame-based practices to potentially embarrass themselves if they don't follow through. They'll write checks to organizations that they hate and insist that they'll cash them if they don't actually follow through. Or they'll do it out of love. They'll decide that they're going to run a marathon or learn a language or something because of somebody they love or they want to devote it to somebody.

The truth is that from the standpoint of epinephrine and getting alert and activated, it doesn't really matter. Epinephrine is a chemical and your brain does not distinguish between doing things out of love or hate, anger, or fear. It really doesn't. All of those promote autonomic arousal and the release of epinephrine.

So I think for most people, if you're feeling not motivated to make these changes, the key thing is to identify not just one, but probably a kit of reasons, several reasons as to why you would want to make this particular change. And being drawn toward a particular goal that you're excited about can be one.

Also being motivated to not be completely afraid, ashamed, or humiliated for not falling through on a goal is another. Just want to briefly mention one little aside there because I've got a friend who's a physician. He's a cardiologist who has a really interesting theory. This is just theory, but I think it will resonate with a lot of people, which is that you've all heard of this molecule dopamine that gives us this sense of reward when we accomplish something.

Well, we also want to be able to access dopamine while we're working towards things. Enjoy the process, as they say, 'cause it has all sorts of positive effects. It gives us energy, et cetera. With my friend, what he says is, there's many, many instances where someone will come to him and say, "You know what?

I'm going to write a book." And he says, "Oh, that's great. I'm sure the book's going to be terrific and you really should write a book." And then they never go do it. And his theory is if you get so much dopamine from the reward of people saying, "Oh yeah, you're absolutely going to be able to do that," you might not actually go after the reward of the accomplishment itself.

So beware these positive reinforcements also. So I suggest that everyone asks themselves, "What is it that I want to accomplish? And what is it that's driving me to accomplish this?" And come up with two or three things, fear-based perhaps, love-based perhaps, or perhaps several of those, in order to ensure alertness, energy, and attention for the task.

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