The Neural Correlations of Olfactory Associative Reward Memories in Drosophila

Abstract

Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous modification of interactions within a gene network functioning within a broader neural network. This distinctive characteristic enables significant neural plasticity, but complicates experimental investigations. A thorough examination of the mechanisms underlying behavioral plasticity must integrate multiple levels of biological organization, encompassing genetic pathways within individual neurons, interactions among neural networks providing feedback on gene expression, and observable phenotypic behaviors. Model organisms, such as Drosophila melanogaster, which possess more simple and manipulable nervous systems and genomes than mammals, facilitate such investigations. The evolutionary conservation of behavioral phenotypes and the associated genetics and neural systems indicates that insights gained from flies are pertinent to understanding human cognition. Rather than providing a comprehensive review of the entire field of Drosophila memory research, we focus on olfactory associative reward memories and their related neural circuitry in fly brains, with the objective of elucidating the underlying neural mechanisms, thereby advancing our understanding of brain mechanisms linked to cognitive systems.

Keywords: Drosophila melanogaster; brain; neural circuits; reward memories.

Figure 1

Overview of the associative water- (or sucrose-) reward paradigms. Before the conditioning process, flies were subjected to a period of water (or food) deprivation lasting from 16 to 24 h. The conditioning protocol involved approximately 50 thirsty (or hungry) flies positioned on the elevator of a T-maze. Initially, the flies were transferred to a CS tube, where an odor (odor A: OCT or MCH) was introduced for 2 min. Subsequently, after a 1 min break in exposure to fresh air, the flies were returned to the elevator and guided to the CS+ tube, which contained filter paper soaked in water (or sucrose) and a different odor (odor B: MCH or OCT) for another 2 min period. Memory retention was evaluated at specified intervals after the training session by offering the flies a choice between two distinct odors.

Figure 2

Overview of the Drosophila olfactory nervous system. The olfactory nervous system of Drosophila is involved in a series of neural processes. Odorants bind to olfactory receptors (ORs) on olfactory receptor neurons (ORNs) located in the sensilla of the antennae lobe (AL) and maxillary palps. The ORNs express specific odorant receptors that facilitate precise olfactory tuning. Subsequently, ORNs send their axons to the antennal lobe, where they form synaptic connections with projection neurons (PNs) in the glomeruli. Uniglomerular PNs transmit olfactory signals to two distinct brain regions in flies: the mushroom bodies (MB) and the lateral horn (LH). Ultimately, this information is relayed to the downstream brain regions through output neurons to influence behavior.

Figure 3

Illustration of the various reward circuits identified in adult Drosophila. The identified circuits associated with behavioral responses to rewards encompassed (A) dopaminergic circuits; (B) the innervation of DANs (PAM) within the MB involved in synaptic connections related to reward across different MB compartments; (C) octopaminergic circuits; and (D) serotoninergic circuits. (MB: mushroom body; PAM: protocerebral anterior medial; FSB: fan-shaped body; EB: ellipsoid body; SEZ: subesophageal zone).