Decomposition of Olfactory Memory by Dopamine Neural Cirucit in Drosophila

Abstract

During the formation of an olfactory memory in Drosophila, the Mushroom Body (MB) receives olfactory cues (Conditioned Stimuli, CS) relayed from the antennal lobe and aversive or reward stimuli (Unconditioned Stimuli; US) from associated dopamine neurons (DANs). It has been shown that the pairing of a CS with dopamine release stimulated by a US is the key process for olfactory conditioning. The simplest mechanism might employ convergence at the MB of a CS and US through two separate and non-interacting circuit pathways. Here we show that the CS and US pathways interact in a novel and significant way to drive memory formation. First, we identified two types of plastic dopamine neurons (pDANs) that assign positive or negative valence to a CS during conditioning. Punishment pDANs are conditioned to respond uniquely to a CS (the CS+) that is associated with a punitive stimulus (US). Appetitive or reward pDANs exhibit coordinate plasticity to a distinct odor (CS-) that is not paired with a punitive US. By screening circuits for training dependent plasticity, we identified neurons that mediate DAN plasticity via a feedback loop from MB output to the pDAN input. A novel extrinsic neuron type we refer to as Recurrent Loop Neurons (RLNs) mediate this loop together with Mushroom body Output Neurons (MBONs). We show that reward pDANs participate in aversive conditioning by utilizing a tripartite feedback circuit involving MBONs, DANs and RLNs to drive memory formation, especially to establish attraction to the CS- odor. We propose a model of bidirectional interaction between US and CS pathways has a specific role in learned binary decisions to memory.