Adverse life events can induce two kinds of memory with opposite valence, 
dependent on timing: "negative" memories for stimuli preceding them and 
"positive" memories for stimuli experienced at the moment of "relief." Such 
punishment memory and relief memory are found in insects, rats, and man. For 
example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock 
training ("forward conditioning" of the odor), whereas after shock-odor training 
("backward conditioning" of the odor) they approach it. Do these 
timing-dependent associative processes share molecular determinants? We focus on 
the role of Synapsin, a conserved presynaptic phosphoprotein regulating the 
balance between the reserve pool and the readily releasable pool of synaptic 
vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor 
faculties unaffected. In contrast, both punishment memory and relief memory 
scores are reduced. These defects reflect a true lessening of associative memory 
strength, as distortions in nonassociative processing (e.g., susceptibility to 
handling, adaptation, habituation, sensitization), discrimination ability, and 
changes in the time course of coincidence detection can be ruled out as 
alternative explanations. Reductions in punishment- and relief-memory strength 
are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued 
both by acutely restoring Synapsin and by locally restoring it in the mushroom 
bodies of mutant flies. Thus, both punishment memory and relief memory require 
the Synapsin protein and in this sense share genetic and molecular determinants. 
We note that corresponding molecular commonalities between punishment memory and 
relief memory in humans would constrain pharmacological attempts to selectively 
interfere with excessive associative punishment memories, e.g., after traumatic 
experiences.