Optogenetically induced reward and ‘frustration’ memory in larval Drosophila

Abstract

Humans and animals alike form oppositely valenced memories for stimuli that predict the occurrence versus the termination of a reward: appetitive 'reward' memory for stimuli associated with the occurrence of a reward and aversive 'frustration' memory for stimuli that are associated with its termination. We characterize these memories in larval Drosophila using a combination of Pavlovian conditioning, optogenetic activation of the dopaminergic central-brain DAN-i1864 neuron, and high-resolution video-tracking. This reveals their dependency on the number of training trials and the duration of DAN-i1864 activation, their temporal stability, and the parameters of locomotion that are modulated during memory expression. Together with previous results on 'punishment' versus 'relief' learning by DAN-f1 neuron activation, this reveals a 2x2 matrix of timing-dependent memory valence for the occurrence/ termination of reward/ punishment. These findings should aid the understanding and modelling of how brains decipher the predictive, causal structure of events around a target reinforcing occurrence.

Rewarding capacity of optogenetically activating a giant GABAergic central-brain interneuron in larvalDrosophila

“…Associative learning by APL activation has a symmetrical 'temporal fingerprint', with a fairly narrow temporal window for presenting the odor (Figure 12D-E). This mirrors what was found for DAN-d1 in the aversive domain , adding to the heterogeneity of internal reinforcement signals (Saumweber et al, 2018;Weiglein et al, 2021;Thoener et al, 2022;adults: Aso and Rubin, 2019;König et al, 2018;Handler et al, 2019).…”

“…Optogenetic activation of APL, using either ChR2XXL or Chrimson as the effector, induces appetitive memory for an associated odor after only one training trial (Figures 12-15). This is similar to odor-sugar associative learning and to the rewarding effect of activating DAN-i1 (Weiglein et al, 2019; Thoener et al, 2022). Associative learning by APL activation has a symmetrical ‘temporal fingerprint’, with a fairly narrow temporal window for presenting the odor (Figure 12D-E).…”

“…We next sought to identify the dopaminergic neurons that mediate the rewarding effect of APL activation. Given the role of the dopaminergic pPAM neurons in larval reward learning (Rohwedder et al, 2016; Saumweber et al, 2018; Schleyer et al, 2020; Thoener et al, 2022), we combined the GAL4/UAS with the lexA/lexAop systems to optogenetically activate APL (APL-GAL4>UAS-ChR2XXL) in animals expressing the pro-apoptotic reaper gene in the pPAM neurons, leading to their ablation (pPAM-lexA>lexAop-reaper). Larvae of the experimental group (APL 55D08 >ChR2XXL; pPAM>reaper) showed reduced odor-APL memory scores relative to genetic controls that lacked either the reaper effector or the pPAM driver for ablation (APL 55D08 >ChR2XXL; pPAM>+ and APL 55D08 >ChR2XXL; +>reaper, respectively) (Figure 18).…”

“…The appetitive memories established by activating APL decay within a few minutes (Figure 12C), as do memories for odor-fructose, odor-DAN-i1, and odor-KC association (Neuser et al, 2005; Kleber et al, 2016; Lyutova et al, 2019; Weiglein et al, 2019; Thoener et al, 2022). Similar to odor-fructose memories and odor-DAN-i1 memories (Paisios et al, 2017; Schleyer et al, 2020), APL-induced memories are expressed as modulations of turning, but not of run speed (Figure 13).…”

“…The appetitive memories established by activating APL decay within a few minutes (Figure 12C), as do memories for odor-fructose, odor-DAN-i1, and odor-KC association (Neuser et al, 2005;Kleber et al, 2016;Lyutova et al, 2019;Weiglein et al, 2019;Thoener et al, 2022).…”