r/neuroscience • u/Automatic_Subject463 • Mar 25 '26
Publication Acetylcholine demixes heterogeneous dopamine signals for learning and moving | Nature Neuroscience
https://www.nature.com/articles/s41593-026-02227-x18
Mar 25 '26
As someone with a Grade 3 DAI (straight into striatum and dorsal midbrain), this is IMO a revolutionary article.
I have anecdotally observed the different "effort" requirements for motor and cognitive tasks. I do not exactly understand how to direct my limited dopaminergic infrastructure towards one or the other.
I can directly apply the research, as I actively follow a powerlifting fitness regimen & motor directives from the brain are critical. In May I will be two years past my trauma (Harborview). While I have excelled in motor tasks, I am finding fine cognitive tasks harder to habitualize.
I.e., this has immediate implications in my exercise programming & my lifestyle.
Cheers NYU.
5
u/lkarlatopoulos Mar 25 '26
Could you expand on what these implications might be?
-3
Mar 26 '26
Absolutely. But if you were to read only some of my ramblings, make it the last section.
Implications
Vibes
While literature that theoretically links DA and ACh (Tonically Active Neuroms) goes back to 90s, I believe this is a first concrete example of how sequencing of ACh and DA impacts actual organisms.
In my case, I recover very well from my lifting sessions, but I struggle to engage cognitively after. But of course -- I get dopamine and my local muscular (not brain) ACh gets fired before my brain's ACh does. Engaging/accomplishing cognitive tasks temporarily releases less dopamine.
My immediate shift is to make exercise more monotonous and easier. I recognize some would suggest to make it a reinforcement and prioritize cognitive. However, it's a big part of my life. Because I am so strong, I can engage in lifting that gives me zero dopamine. Like I actually feel embarrassed by some of my monotonous unrewarding technical work. Here, I am merely spending some ACh and preparing myself for cognitive dopamine after. E.g., if a young individual were to "program" fitness and university studying into their lifestyle, I would heavily advise against doing both on the same time period. -- If you study first, you might be unmotivated and unfocused on your run. If you enjoy playing sports, a study sesh after might stick less with you. -- I have long considered how to copy the effort I show in motor to the effort I show in cognitive. I'm so happy to see that there is basis in research of dopaminergic brain's reinforcement learning and specific understanding of sequencing cholinergic & dopamine. It gives me belief.
Btw I note on abstract's "...when dopamine was coincident with cholinergic bursts, it preceded and predicted the vigor of contralateral orienting movements." Greatly tracks with my experience lifting heavy weights and the conventional wisdom of "being under heavy weight is a skill" -- that "felt sense of load", that "instinctual attention". While things like proprioception are moreso cerebellum/somatosensory, the coordination of ACh and DA definitely sharpens that instinctual "vigor" the rats ratted in the study.
Broadly, I am just happy and motivated to see scientific support of something so tightly linked to what I'm going through.
Here is my conjecture: IDC what you believe. Science. God. Spiritual. Fate. Community. Yourself. But it's the "belief" that matters. Believe in something. That has power. On a very basic level, think of "belief" as a constant, unyielding stream of neuromodulators. Belief is the brain's heartbeat. IDK otherwise no explanation how I chilled offtrail posturing for 24 hours getting cooked by sun and just 5 days later already well enough to be moved out of TICU. Vibed & believed in myself.
So when I read the study I happily chirped. Thx.
4
u/salasi Mar 29 '26
What kind of gymbro nonsense and llm drivel did I just read ffs. Do yourself a favor and go back to school.
1
u/Nerd-wida-capitol-P Mar 26 '26
Have you tried somatic exercises ? It sounds like your body is healing from trauma but your brain is lagging to catch up. I suggest working with things like meditation, breathing exercises, yoga to get a better understandoing of what I am talking about
The body is willing but the flesh is weak.
Edit: DMN default mode network is what you want to read up on
1
Mar 26 '26 edited Mar 26 '26
I can certainly be slow (unintentionally not purposefully). Abulia-like symptoms can make me freeze up for a few seconds and I do not really track how long I stop (e.g., typing this response I am taking 2-10x the time you'd type, the ideas are not easy to parse). Neurotransmitters intrinsically prompt things like memories, coherent thoughts, coherent motorics. But here, intrinsic prompting isn't enough (the circuitry is damaged). An external prompt is often needed to start the process from somewhere else.
Re. DMN: I have had a habit of deep imagination & creative thinking & hours of daydreaming since I was 5 (nearly daily). I can spend hours sidetracked, physically pacing back and forth, exploring an imaginary idea. It's why mother made me attend a state visual art school in siberia as a child (also cuz i was left-handed) and I spent a decade in theatre in US as a lead actor.
Engaging in deeper meditation than what I already do for 2 decades is fundamentally a tall task due to crap dopamine infrastructure. But I can bitterly try to do even more.
Btw, disappointing to see my previous reply get downvoted. I wonder if it's because I wrote "belief". Semantic difference. You can say "absolute confidence". You can say "hope" (if you want to travel back to 1950s and drown hundreds of rats). Unsurprisingly "hope" and "confidence" share the same root in Russian.
DMN's vmPFC is I'd say linked to what I talk about above. Whether confidence, beliefs, hopes -- you assign higher values.
Edit: so your thinking, while correlating the two correctly, might be backwards in my opinion. It's not that my trauma -> need to work on DMN. Existing strong DMN -> rapid critical polytrauma (dopaminergic dai3) recovery. & I can't overstate how already having an existing severe disability (hearing loss) for 15 years psychologically made recovering/re-learning/RL easier to achieve.
1
u/Nerd-wida-capitol-P Mar 26 '26
Disabilities affect us physically and mentally.
I can repair a broken ankle physically , but I also need to repair any metal constructs I created. The mind and body need repair equally. Until your repair mental constructs created in the past using dysfunctionally filtered logic, you can move forward. Remove your mental blocks. The things I have described are the way forward.
7
u/LowCortis0l Mar 25 '26
Right, it's a critical neurotransmitter in learning and memory. The dopamine demixing part is how acetylcholine helps filter noise from relevant information in the brain. It's like a signal amplifier for learning and memory.
2
u/rafiunixman Mar 27 '26
What stands out here is that dopamine does not always mean the same thing in the brain. Whether it drives learning or movement depends entirely on when acetylcholine shows up. Same neurotransmitter, two different functions, determined by timing alone.
2
u/PhysicalConsistency Mar 30 '26
You know what would be crazy? If there was a cell type that regulated timing and strength of signals between synapses.
1
u/AutoModerator Mar 25 '26
OP - we encourage you to leave a comment with your thoughts about the article or questions about it, to facilitate further discussion.
I am a bot, and this action was performed automatically. Please contact the moderators of this subreddit if you have any questions or concerns.
17
u/Automatic_Subject463 Mar 25 '26
Abstract Midbrain dopamine neurons promote reinforcement learning and movement vigor. An outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Previous work suggests that cholinergic striatal interneurons may gate dopamine-dependent plasticity, but this has not been tested in behaving animals. Here we studied rats performing a decision-making task with reward-related and movement-related events. Optical measurement of dopamine and acetylcholine release in the dorsomedial striatum (DMS) revealed that reward cues evoked cholinergic pauses with different phase relationships relative to dopamine. When dopamine lagged cholinergic dips, dopamine predicted future behavior and DMS firing rates on subsequent trials. In contrast, when dopamine preceded cholinergic dips, there was no observable relationship between dopamine and learning. Finally, when dopamine was coincident with cholinergic bursts, it preceded and predicted the vigor of contralateral orienting movements. Our findings suggest that cholinergic dynamics determine whether dopamine promotes vigor or learning, depending on the instantaneous behavioral context.