Attention Deficit & Hyperactivity in a Drosophila Memory Mutant
Action selection is modulated by external stimuli either directly or via memory retrieval. In a constantly changing environment, animals have evolved attention-like processes to effectively filter the incoming sensory stream. These attention-like processes, in turn, are modulated by memory. The neurobiological nature of how attention, action selection and memory are inter-connected is unknown. We describe here new phenotypes of the memory mutant radish in the fruit fly Drosophila.
In several different behavioral and electrophysiological assays, radish mutant flies revealed a reduced attention span, more frequent and more random alternations in choice behavior, as well as a well-defined oscillatory hyperactivity in both brain activity and behavior. Specifically, radish mutants showed impaired optomotor behavior in a walking maze, despite showing optomotor behavior in flight. In the maze, radish mutant flies exhibited more random alternations in choice behavior at each branch point than wildtype flies. Furthermore, recordings of local field potentials in the fly brain revealed a shorter attention span when the flies were presented with two competing visual patterns, as well as a more random alternation of brain activity in response to these patterns. These brain recordings also revealed a peak at ~1.6Hz in the power spectrum of the local field potentials, where no such peak could be observed in the wildtype animals. The same oscillatory hyperactivity at ~1.6Hz could be observed in turning behavior measured in tethered flight, with visual patterns surrounding the fly. These phenotypes were rescued by transgenically expressing the Radish protein in a mutant background during fly development, but not in the adult. In addition, administration of a drug commonly used to treat Attention-Deficit Hyperactivity Disorder (ADHD) in humans, methylphenidate (Ritalin) also rescued the optomotor behavior, the reduced attention span and abolished the ~1.6Hz hyperactivity in treated flies.
We conclude that the circuits defined by radish expression in the fly brain are involved in modulating the tempo of stimulus selection and suppression. It remains to be found out if methylphenidate also rescues the radish memory defect. A failed rescue would indicate that the phenotype discovered here is not the cause for radish’s memory defect. Our findings allow for the first time to study how action selection is modulated by the interplay of external stimuli, attention and memory in a genetically tractable model organism.