Reinforcement signaling of punishment versus relief in fruit flies

Abstract

Painful events establish opponent memories: cues that precede pain are remembered negatively, whereas cues that follow pain, thus coinciding with relief are recalled positively. How do individual reinforcement-signaling neurons contribute to this "timing-dependent valence-reversal?" We addressed this question using an optogenetic approach in the fruit fly. Two types of fly dopaminergic neuron, each comprising just one paired cell, indeed established learned avoidance of odors that preceded their photostimulation during training, and learned approach to odors that followed the photostimulation. This is in striking parallel to punishment versus relief memories reinforced by a real noxious event. For only one of these neuron types, both effects were strong enough for further analyses. Notably, interfering with dopamine biosynthesis in these neurons partially impaired the punishing effect, but not the relieving after-effect of their photostimulation. We discuss how this finding constraints existing computational models of punishment versus relief memories and introduce a new model, which also incorporates findings from mammals. Furthermore, whether using dopaminergic neuron photostimulation or a real noxious event, more prolonged punishment led to stronger relief. This parametric feature of relief may also apply to other animals and may explain particular aspects of related behavioral dysfunction in humans.

One-trial learning in larval Drosophila

“…In adult Drosophila, a single trial of odor preceding electroshock punishment or sugar reward can establish aversive or appetitive associative memory, respectively (Tully and Quinn 1985;Beck et al 2000;Colomb et al 2009;Scheunemann et al 2013). In addition, onetrial learning can be demonstrated upon pairing odor with the optogenetic activation of subsets of dopaminergic neurons innervating the mushroom body in adult flies (Aso and Rubin 2016;König et al 2018).…”

Associative learning in larval and adult Drosophila is impaired by the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine

“…For the memory assays, we followed the procedures described in König et al (2018), unless mentioned otherwise. Flies were loaded into a small transparent tube in a custom-made set-up (CON-ELEKTRONIK, Greussenheim, Germany) and were trained and tested at 23-25°C and 60-80% relative humidity.…”

“…To ensure a withinexperiment error rate below 5%, a Bonferroni-Holm (BH) correction for multiple comparisons was employed (Holm, 1979). Sample sizes (biological replications) were estimated based on previous studies with small to medium effect sizes (König et al, 2018;Weiglein et al, 2019). None of the specific experiments reported here had previously been performed in our laboratory, although the basic behavioral paradigms are regularly used.…”

“…PPL1-01 and MB-MP1), as covered by the Split-GAL4 driver strain MB320C (Aso et al, 2014). This neuron, when optogenetically activated, carries an internal punishment signal sufficient to establish an aversive associative memory when paired with an odor (Aso and Rubin, 2016;Hige et al, 2015;König et al, 2018) (Fig. 4A, left-most box plot).…”

Is it pain if it does not hurt? On the unlikelihood of insect pain

“…Just as mammalian nociceptors send information to the brain via dorsal horn neurons in the spinal cord (Purves et al 2012), insect nociceptors synapse onto neurons that reach the brain (e.g., larval D. melanogaster; Gerhard et al 2017). Although the entire nociceptive pathway has not yet been delineated in any insect, it is known that nociceptive information is processed in two higher-order integratory areas, the mushroom bodies (Waddell 2013;Konig et al 2018) and the central complex (Hu et al 2018). These two areas are among the most complex in the insect brain, and are key for navigation, learning, memory, and other complex cognitive tasks (Barron and Klein 2016; Kinoshita and Homberg 2017).…”