Aversive teaching signals from individual dopamine neurons in larval Drosophila show qualitative differences in their temporal “fingerprint”

Abstract

Dopamine serves many functions, and dopamine neurons are correspondingly diverse. We use a combination of optogenetics, behavioral experiments, and high-resolution videotracking to probe for the functional capacities of two single, identified dopamine neurons in larval Drosophila. The DAN-f1 and the DAN-d1 neuron were recently found to carry aversive teaching signals during Pavlovian olfactory learning. We enquire into a fundamental feature of these teaching signals, namely their temporal "fingerprint". That is, receiving punishment feels bad, whereas being relieved from it feels good, and animals and humans alike learn with opposite valence about the occurrence and the termination of punishment (the same principle applies in the appetitive domain, with opposite sign). We find that DAN-f1 but not DAN-d1 can mediate such timing-dependent valence reversal: presenting an odor before DAN-f1 activation leads to learned avoidance of the odor (punishment memory), whereas presenting the odor upon termination of DAN-f1 activation leads to learned approach (relief memory). In contrast, DAN-d1 confers punishment memory only. These effects are further characterized in terms of the impact of the duration of optogenetic activation, the temporal stability of the memories thus established, and the specific microbehavioral patterns of locomotion through which they are expressed. Together with recent findings in the appetitive domain and from adult Drosophila, our results suggest that heterogeneity in the temporal fingerprint of teaching signals might be a more general principle of reinforcement processing through dopamine neurons.

Optogenetically induced reward and ‘frustration’ memory in larval Drosophila

“…In addition, upon forward training we observed that the runs towards the odour were faster than those away from it (Fig. 2C); this was surprising given that in 13 previous datasets tendencies for such run speed modulation, which can be recognized in about half of the cases, had never reached statistical significance (Paisios et al, 2017;Saumweber et al, 2018;Schleyer et al, 2015;Schleyer et al, 2020;Thane et al, 2019;Toshima et al, 2019;Weiglein et al, 2019;Weiglein et al, 2021). In any event,…”

“…Procedures followed Saumweber et al (2018) and Weiglein et al (2021). Variations in the following procedures will be mentioned in the Results section.…”

“…Whether the mechanisms of frustration memory established by termination of DAN-i1 864 activation differ from those of the likewise aversive memory established by unpaired presentations of odour and DAN-i1 864 activation (Schleyer et al, 2018(Schleyer et al, , 2020 remains to be tested. The DAN-f1 neuron, in contrast, supports aversive punishment memory upon forward training and appetitive 'relief' memory upon backward training (Weiglein et al, 2021; using SS02180-Gal4 as the driver, henceforth DAN-f1 2180 ) (adults: Aso and Rubin, 2016;Handler et al, 2019;König et al, 2018). Whereas for DAN-f1 2180Weiglein et al (2021 have characterized punishment and relief memories in some detail, no further analysis has been performed for the reward and frustration memories established by DAN-i1 864 activation.…”

“…The DAN-f1 neuron, in contrast, supports aversive punishment memory upon forward training and appetitive 'relief' memory upon backward training (Weiglein et al, 2021; using SS02180-Gal4 as the driver, henceforth DAN-f1 2180 ) (adults: Aso and Rubin, 2016;Handler et al, 2019;König et al, 2018). Whereas for DAN-f1 2180Weiglein et al (2021 have characterized punishment and relief memories in some detail, no further analysis has been performed for the reward and frustration memories established by DAN-i1 864 activation. Here, we undertake such an analysis to provide a more complete picture of the timing-dependent valence reversal conferred by dopaminergic neurons.…”

Different dopaminergic neurons signal absolute and relative aversive value in the Drosophila mushroom body

“…Aversive experience is uniquely coded at the KC-MBON-g1ped>ab and -MBON-g2a´1 junctions PPL1 DANs reinforce a range of aversive memories with differing strength and persistence 34,[36][37][38]55,58,79,80 . Our data provide new insight into the functional diversity of these anatomically discrete DANs (Fig.…”