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

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.

Development of a Classical Conditioning Task for Humans Examining Phasic Heart Rate Responses to Signaled Appetitive Stimuli: A Pilot Study

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans.

Unc13A and Unc13B contribute to the decoding of distinct sensory information in Drosophila

The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca2+ channels and the (m)unc13 family priming factors, Unc13A and Unc13B. Importantly, coupling distance defines release components with distinct STP characteristics. Here, we show that while Unc13A and Unc13B both contribute to synaptic signalling, they play distinct roles in neural decoding of olfactory information at excitatory projection neuron (ePN) output synapses. Unc13A clusters closer to Ca2+ channels than Unc13B, specifically promoting fast phasic signal transfer. Reduction of Unc13A in ePNs attenuates responses to both aversive and appetitive stimuli, while reduction of Unc13B provokes a general shift towards appetitive values. Collectively, we provide direct genetic evidence that release components of distinct nanoscopic coupling distances differentially control STP to play distinct roles in neural decoding of sensory information.

The role of the vestibular system in value attribution to positive and negative reinforcers

Somatic inputs originating from bioregulatory processes can guide cognition and behavior. One such bodily signal, mostly overlooked so far, is represented by visuo-vestibular coupling and its alteration, which in extreme cases may result in motion sickness. We argued that the inherently perturbed interoceptive state that follows can be a powerful determinant of human motivated behavior, resulting in a blunted response to appetitive stimuli and an exaggerated response to noxious ones. We sought to assess such differential impact of visuo-vestibular mismatches on value through a task involving conflict monitoring. We therefore administered to 42 healthy participants a modified version of the Flankers task, in which distractors (arrows, pointing in either a congruent or incongruent direction) signaled the availability of monetary incentives (gains, losses, or neutral trials). While performing the task, participants received either galvanic vestibular stimulation (GVS), or sham stimulation. We have found impaired behavioral performances when value, which was attached to task-irrelevant information, was at stake. Gains and losses, interestingly, dissociated, and only the latter caused enhanced interference costs in the task, suggesting that negative incentives may be more effective in capturing human attention than positive ones. Finally, we have found some weak evidence for GVS to further increase the processing of losses, as suggested by even larger interference costs in this condition. Results were, however, overall ambiguous, and suggest that much more research is needed to better understand the link between the vestibular system and motivation.HighlightsVisuo-Vestibular mismatches may be important somatic markers affecting the evaluation of reinforcers;When attached to distractors, value information impairs behavioral performance for the task at hand;Trials in which potential losses were at stake were associated with larger interference costs arising from conflicting information between the target and the flankers;GVS (Right-Anodal) may further increase the interference caused by losses, but the evidence in this respect was ambiguous and inconclusive;

Experience-dependent refinement of natural appetitive visual behavior in mice

Specific features of visual objects innately draw orienting and approach responses in animals, and provide natural signals of potential reward. In addition, the rapid refinement of innate approach responses enhances the ability of an animal to effectively and conditionally forage, capture prey or initiate a rewarding social experience. However, the neural mechanisms underlying how the brain encodes naturally appetitive stimuli and conditionally transforms stimuli into approach behavior remain unclear. As a first step towards this goal, we have developed a behavioral assay to quantify innate, visually-evoked approach behaviors in freely moving mice presented with simple, computer generated stimuli of varying sizes and speeds in the lower visual field. We found that specific combinations of stimulus features selectively evoked innate approach versus freezing behavioral responses. Surprisingly, we also discovered that prey capture experience selectively modified a range of visually-guided appetitive behaviors, including increasing the probability of approach and pursuit of moving stimuli, as well as altering those visual features that evoked approach. These findings will enable the use of sophisticated genetic strategies to uncover novel neural mechanisms underlying predictive coding, innate behavioral choice, and flexible, state-dependent processing of stimuli in the mouse visual system.

Beer? Over here! Examining attentional bias towards alcoholic and appetitive stimuli in a visual search eye-tracking task

Rationale: Experimental tasks that demonstrate alcohol-related attentional bias typically expose participants to single-stimulus targets (e.g., addiction stroop, visual probe, anti-saccade task), which may not correspond fully with real-world contexts where alcoholic and non-alcoholic cues simultaneously compete for attention. Moreover, alcoholic stimuli are rarely matched to other appetitive non-alcoholic stimuli. Objectives: To address these limitations by utilising a conjunction search eye-tracking task and matched stimuli to examine alcohol-related attentional bias. Methods: Thirty social drinkers (Mage = 19.87, SD = 1.74) were asked to detect whether alcoholic (beer), non-alcoholic (water) or non-appetitive (detergent) targets were present or absent amongst a visual array of matching and non-matching distractors. Both behavioural response times and eye-movement dwell time were measured. Results: Social drinkers were significantly quicker to detect alcoholic and non-alcoholic appetitive targets relative to non-appetitive targets in an array of matching and mismatching distractors. Similarly, proportional dwell time was lower for both alcoholic and non-alcoholic appetitive distractors relative to non-appetitive distractors, suggesting that appetitive targets were relatively easier to detect. Conclusions: Social drinkers may exhibit generalised attentional bias towards alcoholic and non-alcoholic appetitive cues. This adds to emergent research suggesting that the mechanisms driving these individual’s attention towards alcoholic cues might ‘spill over’ to other appetitive cues, possibly due to associative learning.