Cellular and circuit mechanisms of olfactory associative learning in Drosophila

Abstract

Recent years have witnessed significant progress in understanding how memories are encoded, from the molecular to the cellular and the circuit/systems levels. With a good compromise between brain complexity and behavioral sophistication, the fruit fly Drosophila melanogaster is one of the preeminent animal models of learning and memory. Here we review how memories are encoded in Drosophila, with a focus on short-term memory and an eye toward future directions. Forward genetic screens have revealed a large number of genes and transcripts necessary for learning and memory, some acting cell-autonomously. Further, the relative numerical simplicity of the fly brain has enabled the reverse engineering of learning circuits with remarkable precision, in some cases ascribing behavioral phenotypes to single neurons. Functional imaging and physiological studies have localized and parsed the plasticity that occurs during learning at some of the major loci. Connectomics projects are significantly expanding anatomical knowledge of the nervous system, filling out the roadmap for ongoing functional/physiological and behavioral studies, which are being accelerated by simultaneous tool development. These developments have provided unprecedented insight into the fundamental neural principles of learning, and lay the groundwork for deep understanding in the near future.

Keywords: Drosophila; dopamine; genetics; learning; memory; mushroom body; neuronal circuit; olfactory.

Figure 1.

Simplified diagram of the anatomical connectivity and information processing that underlies olfactory learning in Drosophila. A. Simplified diagram of the olfactory pathway through the mushroom body (MB) and mushroom body output neurons (MBONs), highlighting the major anatomical structures involved in learning. Connections to the lateral horn are not shown. Gray arrows indicate the inward information flow from peripheral olfactory sensory receptors. ORNs: olfactory receptor neurons, PNs: projection neurons, KCs: Kenyon Cells, DAN: dopaminergic neuron(s), MBON: mushroom body output neuron, PPL1/2: paired posterior lateral (dopaminergic) neurons, PAM: protocerebral anterior medial (dopaminergic) neurons. B. Drawing of the mushroom body, showing the major anatomical subdivisions and classes of neurons relevant for learning. Anatomical compartments (γ1-γ5, α2, α3, α′3) are outlined with dashed lines. For clarity, only one γ KC and one α/β KC are drawn (out of ~2500 total); likewise, two MBONs are drawn (out of 34 total). C. Flowchart highlighting major connections in the olfactory pathway that are critical for olfactory learning and memory. DPM: dorsal paired medial neuron, DAL: dorsal anterior lateral, APL: anterior paired lateral neuron.