Pain is so close to pleasure: the same dopamine neurons can mediate approach and avoidance in Drosophila

Abstract

In mammals, dopamine is considered a central neuromodulator involved in all kinds of rewarding experiences ('common currency' hypothesis). In insects, the role of dopaminergic neurons in aversive stimuli was discovered before dopaminergic neurons were found to also be involved in processing appetitive stimuli. Here, we screened about 50 transgenic Drosophila lines, representing different subpopulations of dopaminergic neurons for their ability to sustain approach or avoidance behavior, when activated optogenetically in four different operant self-stimulation paradigms. None of the lines sustain consistent behavioral valence in all experiments. Individual lines sustain approach in one experiment and avoidance in another. One line mediated strong avoidance early in the experiment and weak approach in later stages. The evidence presented here appears to contradict a 'common currency' dopamine function in flies. Instead, different dopaminergic neurons convey valence in a context-dependent and flexible manner, reflecting the genetic heterogeneity of the dopaminergic neuronal population.

Optogenetic induction of appetitive and aversive taste memories in Drosophila

“…Interestingly, activation of the PAM-β2β′2a subset labeled by MB301B-Gal4 produced a higher preference for the salt CS during training, yet no sustained changes in taste preference during STM or LTM testing were observed ( Figure 4G and H ). This demonstrates that the reward signaling associated with PAM cell activation occurs on multiple timescales to produce acute, short-, or long-term changes in behavior, consistent with past results demonstrating the context-dependent effects of DAN activation ( Rohrsen et al, 2021 ) Notably, the trend toward lower salt preference during testing in this experiment may reflect a reduced salt drive due to increased salt consumption during training.…”

Reward expectations direct learning and drive operant matching in Drosophila

“…These motor-related DAN signals would presumably modify synaptic connections in the MB, and such off-task plasticity could generate important variability in synaptic weights and choice behavior. Interestingly, recent work has also found that these same DANs do not have a consistent effect on action-reward learning in a purely operant task ( 63 ). This suggests that motor-related DAN signals are not the substrate for operant learning, and MB plasticity may specifically act to link sensory cues to rewarding actions.…”

“…Rather, the choices made by the fly dictate the odors and rewards experienced, a hallmark of operant-learning tasks. However, unlike purely operant tasks, where animals learn that specific actions lead to rewards or punishment ( 62 , 63 ), flies in our task have to learn to perform stimulus-dependent actions. This relationship between stimulus, action, and reward is very similar to the dynamic foraging tasks where operant matching has been observed in other species ( 11 – 14 ).…”

A dopaminergic memory circuit drives acute valence via multiple neurotransmitters

“…Conversely, in a low baseline activity state, stimulation of these cells would be expected to result in a large effect. Recent studies have described high variability between different optogenetic valence assays [62,65], suggesting that optogenetic valence is not generalizable between different behavioral tasks. Since different sensory modalities and/or associative circuits may be employed for different tasks, this is not unexpected.…”

“…As such, an important question goes unanswered: is DAN activity in isolation also capable of driving acute valence behavior? To our knowledge, only one other study has explored this question, demonstrating DAN-mediated acute valence, and finding this property to be heterogeneous across different contexts [65].…”