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86BillionFireflies t1_j24fby9 wrote

Neuroscience PhD here: Dopamine does different things in different places. Asking why one group of dopamine releasing neurons can't substitute for another is like saying "my toilet valve is broken, but the valve in my shower is fine, so shouldn't my toilet work anyway?"

Dopamine releasing neurons in the substantia nigra and the dopamine releasing neurons in other areas have 1 thing in common, which is the neurotransmitter they use. But what neurotransmitter they use is relatively unimportant to their function. What's far more important is what neurons they get input from, how those inputs are processed, and what neurons they connect to.

Any given group of neurons that releases dopamine can only release dopamine where their axons are, and that dopamine cannot freely diffuse throughout the brain. This is the whole point of synapses: to help confine the spread of neurotransmitters so that neurotransmitters can act as signals from one neuron to another instead of broadcast signals.

If this seems like a significant departure from how you're used to thinking about neurotransmitters, GOOD. Neurotransmitters do not have functions, neurons do. Repeated with emphasis: NEUROTRANSMITTERS DO NOT HAVE FUNCTIONS, NEURONS DO. Two different neurons can use the same neurotransmitter for totally different functions. Dopamine, for example, is also used in the control of lactation, which is totally unrelated to its role in the control of movement.

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Omega099 t1_j26ccza wrote

The last paragraph you wrote is extremely important to note and thank you for stating that, the circuitry is much more interesting haha

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86BillionFireflies t1_j26kguu wrote

Very much so! If you're curious about neural circuits, check out the app Neuronify.. it's a simple spiking neuron simulator, you can play around with using neurons with different properties to create circuits with multiple stable states, circuits that generate periodic output sequences, and circuits that do specific things in response to an input.

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AxelBoldt t1_j27pcez wrote

But given that, how come we treat Parkinson's by flooding the brain with dopamine? We wouldn't shovel valves into an apartment to repair a broken toilet valve.

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86BillionFireflies t1_j28hxch wrote

>how come we treat Parkinson's by flooding the brain with dopamine

That's the neat thing! You don't.

You flood the brain with stuff to make dopamine, which lets the surviving SNc neurons release more dopamine, essentially amplifying the signals of the ones that are left. If they all died, L-DOPA treatment wouldn't work. Again, the really important thing is the neurons, what inputs they get, how they process those inputs, and where they send their outputs, not which chemical they are releasing. In fact, most work on realistically simulating the activity of networks of neurons doesn't even bother to simulate neurotransmitters in any way, except to say "when this neuron fires, that one gets excited by +2millivolts after a delay of 2ms" or something to that effect.

So in the valve analogy, it's like we're increasing the water pressure so that the semi-busted toilet valve can still sort of function.

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AxelBoldt t1_j294iox wrote

Thank you for that. Do the dopamine-releasing neurons take up L-dopa, turn it into dopamine, and then release it at the synapse?

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86BillionFireflies t1_j29xtcv wrote

That's exactly right! In the synthesis of dopamine, converting tyrosine to L-DOPA is the slowest step, so having extra L-DOPA available significantly increases dopamine production.

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AxelBoldt t1_j2ack46 wrote

And we're not concerned that, with L-dopa treatment, some dopamine-releasing neurons that aren't affected by Parkinson's will now release too much dopamine? I would be afraid of schizophrenia for example.

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86BillionFireflies t1_j2b1pvx wrote

That's what side effects are. Anytime you take psychoactive medications, they're going to mess with a thousand different brain systems that ALSO happen to use the neurotransmitter(s) affected by the drug, but were functioning normally. Thankfully, the brain is usually pretty good at compensating for stuff like that (which is why drug tolerance is a thing). Otherwise, side effects would probably be a LOT worse in general.

But when you say you're worried about schizophrenia, that's still thinking about it wrong. Schizophrenia is not caused by a simple overabundance of dopamine, it's caused by some kind of complex disturbance in the activity of one or more networks of brain circuits. The fact that some of those circuits have some dopaminergic components, and that some of the drugs that can partially alleviate symptoms affect dopamine among other neurotransmitters does not make dopamine central to schizophrenia.

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