Transcript:  

Here we go. I've drawn in all my psychosis circuit. Let's see how it normally works.

GABA would come out and inhibit the next guy so that it's controlling the amount of glutamate that comes out of the other end of the neuron.

So, it doesn't kick that blue neuron too hard. It's going to stimulate it. Oh, there's a little bit of dopamine coming out. See that? Whoop.

Now, just to control it even more, you've got your acetylcholine neuron over here. It's going to spit acetylcholine on here, and it's going to excite the M5 receptor, and look at the dopamine at the end. Whoop. There it goes again.

And we ain't done yet. Acetylcholine comes out of the other end, talking to the nicotinic receptor which makes dopamine go, whoop. But this is just normal.

This is just normal regulation. You want to be able to control that dopamine. It's pretty important to control. So, I've got 3 ways, 3 neurotransmitters.  

Both ends of the nerve. I've got that sucker locked in. Psychosis. Something happens in the cortex to make a sick GABA neuron.

What do you suppose happens if GABA doesn't work? Watch the purple. Wow. Now, GABA's not inhibiting the next guy. What happens? Whoop.

What's going to happen to the other end of the dopamine neuron if I just did that? Watch. Oh, wow. Okay. That's psychosis.

And so, what do we do? We find a drug and knock down every damn D2 receptor in Colorado Springs to stop that blue cloud from harming our patients.

Of course, it's going to do it everywhere in the brain, including a lot of receptors you don't want to do it,

and do it so highly that it causes side effects, but that's the cost of doing business.

That's what we've been doing for 70 years.

Now, enter this stimulation or procholinergic, treatment for delusions and hallucinations, positive symptoms.

And there's 2 pathways. Let's talk about the first one, the brainstem M4.

So, you're supposed to again, say what you're going to say. I'm going to say it in words. Then I'm going to say what I said with the cartoon.

M4 stimulation, procholinergic treatment of positive symptoms. You give an agonist for M4 at those presynaptic sites I showed you, on those 2 cholinergic neurons, one on the hindbrain, we'll show you later one in the striatum.

Ready? It treats positive symptoms because that agonist at that presynaptic site shuts off cholinergic stimulation of dopamine release.

Ready? Here's my psychotic circuit. Way too much dopamine because this goes down, this excitatory things kicks sucker, out comes dopamine, and da-da-da-da. Here comes a cholinergic agonist for M4. Vroom, boom.

It's going to stimulate inhibition. What's going to happen to the acetylcholine cloud there, the pink cloud? Higher or lower? Lower.

What's going to happen to the dopamine cloud on the other end of the dopamine neuron? Ah. My delusions are already fading. Now, what happens if, da-da-da-da, this guy goes here? Vroom, boom. This pink cloud goes down, and the dopamine cloud goes down.  

I ain't even talked to no damn D2 receptor, thank you very much. I don't have dopamine release. That's so bad. Pretty cool.