Abstract-1
Learning is driven by prediction errors, which determine what is learned, and salience, which controls the learning rate. Dopamine in the nucleus accumbens correlates with prediction errors, but salience mechanisms are less clear. We hypothesized that acetylcholine acts as a salience signal, as it regulates dopamine-induced plasticity. To test this, we recorded acetylcholine and dopamine dynamics in rats across three learning tasks. Our findings reveal a characteristic pattern of evolving neuromodulator responses during learning. First, indiscriminate cholinergic dips appeared, then dopamine responses differentiated based on predicted value, followed by the cholinergic dips also varying by value. Stable performance required this full pattern, and acetylcholine dips could be decoupled from value by changing reward contingencies. The observed acetylcholine dynamics fit an associative salience term predicted by hybrid attentional associative learning models, suggesting that dopamine and acetylcholine act complementarily to determine the content and rate of learning.
Zhewei Zhang, Kauê Machado Costa, Yizhou Zhuo, Guochuan Li, Yulong Li, Geoffrey Schoenbaum. Accumbal acetylcholine signals associative salience during learning. bioRxiv, 2025-04. [LINK]
Abstract-2
Dopamine release in the nucleus accumbens (NAcc) changes quickly in response to errors in predicting events like reward delivery but also slowly ramps up when animals are moving toward a goal. This ramping has attracted much recent attention, as there is controversy regarding its computational role and whether they are driven by dopamine neuron firing or local circuit mechanisms. If the latter is true, cholinergic transmission would be a prime candidate mechanism, and acetylcholine and dopamine signals should be positively correlated during behavior, particularly during motivated approach. However, in the dorsal striatum, striatal cholinergic interneurons typically “dip” their activity when reward or associated cues are presented, in opposition to dopamine, and acetylcholine and dopamine release is generally anti-correlated in vivo. Furthermore, acetylcholine and dopamine have opposing effects on downstream striatal projection neurons (SPNs), which suggests that cholinergic dips create a permissive window for dopamine to drive plasticity. These studies therefore suggest that dopamine and acetylcholine should be anti-correlated during behavior. We tested between these hypotheses by simultaneously recording accumbal dopamine and acetylcholine signals in rats executing a task involving motivated approach. We found that dopamine ramps were not coincidental with changes in acetylcholine. Instead, acetylcholine was positively, negatively, or uncorrelated with dopamine depending on the task phase. Our results suggest that accumbal dopamine and acetylcholine dynamics are largely independent but may combine to engage different postsynaptic mechanisms depending on task demands..
Kauê Machado Costa, Zhewei Zhang, Douglas Deutsch, Yizhou Zhuo, Guochuan Li, Yulong Li, Geoffrey Schoenbaum. Dopamine and acetylcholine correlations in the nucleus accumbens depend on behavioral task states. Current Biology, 2025-03. [LINK]
Speaker: Yingjun Tang
Time: 9:00 am, 2025/05/26
Location: CIBR A622
