Olfactory learning modulates a neural circuit mediating innate odor-guided behavior in Drosophila

Behavior is often categorized as being innate or learned, with the specific circuits being assigned to one of these categories. In Drosophila, neural circuits mediating an innate behavioral response are considered as being "hard-wired", as activation of these neuronal pathways leads to stereotyped behaviors. However, only a limited number of studies assessed whether innate behaviors and their underlying neural circuits are plastic or show experience-dependent modulation. Here, we show that experience modulates second-order olfactory neurons involved in innate behavioral responses. We focus on the neural circuit defined by multiglomerular projection neurons (mPNs) that target the lateral horn, a structure relevant in the genesis of innate behavior. We show that mPNs, coding for odor attraction, are bidirectionally modulated after olfactory associative learning: when an olfactory stimulus is paired with an aversive electric shock, the activity of these neurons is decreased, while when the odor is paired with a sucrose-reward they are potentiated. We further show that this modulation requires glutamate and serotonin signaling, and that downstream third-order neurons are consequently affected. The bidirectional nature of the plasticity in these neurons is reflected in behavior: silencing mPN activity leads to odor avoidance, while artificial activation induces approach. While output from the mPNs is not required in aversive olfactory conditioning, silencing these neurons during retrieval of appetitive memories leads to a significant memory impairment. Artificially activating these neurons during odor presentation is sufficient to generate a 3 h appetitive memory. Our study in flies shows that a neural circuit coding for innate odor attraction can contribute to learned behavior, is modulated by olfactory learning and can provide reward-like reinforcement.