Octopamine in the mushroom body circuitry for learning and memory

Abstract

Octopamine, the functional analog of noradrenaline, modulates many different behaviors and physiological processes in invertebrates. In the central nervous system, a few octopaminergic neurons project throughout the brain and innervate almost all neuropils. The center of memory formation in insects, the mushroom bodies, receive octopaminergic innervations in all insects investigated so far. Different octopamine receptors, either increasing or decreasing cAMP or calcium levels in the cell, are localized in Kenyon cells, further supporting the release of octopamine in the mushroom bodies. In addition, different mushroom body (MB) output neurons, projection neurons, and dopaminergic PAM cells are targets of octopaminergic neurons, enabling the modulation of learning circuits at different neural sites. For some years, the theory persisted that octopamine mediates rewarding stimuli, whereas dopamine (DA) represents aversive stimuli. This simple picture has been challenged by the finding that DA is required for both appetitive and aversive learning. Furthermore, octopamine is also involved in aversive learning and a rather complex interaction between these biogenic amines seems to modulate learning and memory. This review summarizes the role of octopamine in MB function, focusing on the anatomical principles and the role of the biogenic amine in learning and memory.

Figure 1.

Octopaminergic neurons innervate the mushroom body. (A–E) Four octopaminergic cell types that arborize in the MB identified on an electron microscopic level using FlyWire neuroglancer. The VPM5 cell type has not yet been identified in the FlyWire data set. (B) The APL neuron innervates all parts of the MB. (C) Two VUMa2 neurons project from the antennal lobe via the iACT to both calyces and the lateral horn. (D) The paired VPM3 cells innervate the contralateral calyx and lobes, the fan-shaped body, parts of the dorsolateral protocerebrum, and the SEZ. (E) The VPM4 cell type arborizes in the contralateral γ-lobe and innervates the dorsomedial and -lateral protocerebrum as well as the SEZ. (F) Overview of the MB (gray) and the appropriate OA release sites (colored) of the four different octopaminergic cell types shown in B–E and the VPM5 cell type. Based on the data from Busch et al. (2009), Aso et al. (2014), and the analysis of the whole brain EM volume using FlyWire neuroglancer (Zheng et al. 2018; Dorkenwald et al. 2022, 2023). (APL) Anterior paired lateral, (Ca) calyx, (iACT) inner antennocerebral tract, (SEZ) subesophageal zone, (VPM) ventral paired median, (VUM) ventral unpaired median.

Figure 2.

Ultrastructure of octopaminergic neurons in the mushroom body. (A–D) Example images of the ultrastructure of the MB-innervating OA cell types show large dense-core vesicles (DCVs, arrowheads), synaptic vesicles (SVs, open arrowheads), and potential SV release sites (t-bars, open arrowheads). FlyWire neuroglancer was used to investigate the morphology of OANs in the whole brain EM volume (Zheng et al. 2018; Dorkenwald et al. 2022). (A) The APL neuron contains mostly SVs and only a few DCVs in all areas. Example boutons from the calyx (A1), α- (A2), β- (A3), α′- (A4), and γ-lobes (A5). (B) DCVs and SV release sites in a VUMa2 cell bouton in the calyx. (C) Ultrastructure of the VPM3 neuron in the γ- (C1) and α′-lobe (C2) and the calyx (C3). (D) The VPM4 cell innervates the complete γ-lobe. DCVs, as well as SVs and their release sites, are visible in the γ1 (D1), γ2 (D2), γ3 (D3), γ4 (D4), and γ5 (D5) compartments. Scale bars, 300 nm.