Appetitive Learning Requires the Alpha1-Like Octopamine Receptor OAMB in theDrosophilaMushroom Body Neurons

Abstract

Associative learning is a fundamental form of behavioral plasticity. Octopamine plays central roles in various learning types in invertebrates, however the target receptors and underlying mechanisms are poorly understood. Drosophila provides a powerful system to uncover the mechanisms for learning and memory. Here, we report that OAMB in the mushroom body neurons mediates the octopamine’s signal for appetitive olfactory learning. The octopamine receptor OAMB has two isoforms (OAMB-K3 and OAMB-AS), differing in the third cytoplasmic loop and downstream sequence. The activation of each OAMB isoform increases intracellular Ca2+ similar to the alpha1 adrenergic receptor, while OAMB-K3 additionally stimulates cAMP production. The oamb null mutants showed severely impaired learning in appetitive olfactory conditioning that tests flies’ capacity to learn and remember the odor associated with sugar reward. This deficit was also seen in the hypomorphic mutant with reduced OAMB expression in the mushroom bodies, the brain structure crucial for olfactory conditioning. Consistently, the oamb mutant’s learning phenotype was fully rescued by conditional expression of either OAMB isoform in the mushroom body αβ and γ neurons. These results indicate that the OAMB receptor is a key molecule mediating the octopamine’s signal for appetitive olfactory learning and its functional site is the mushroom body αβ and γ neurons. This study represents a critical step forward in understanding the cellular mechanism and neural circuit mediating reward learning and memory.

Functional neuroanatomy of Drosophila olfactory memory formation

“…2; Schwaerzel et al 2003;Kim et al 2007). Similarly, optoor thermogenetic stimulation of octopaminergic neurons (OAn) is sufficient for appetitive learning (Schroll et al 2006;Burke et al 2012), and mutants for the expression of the octopamine receptor, OAMB, in the a/b and g MBn are impaired in reward learning (Kim et al 2013). These observations are all consistent with the original idea that the rewarding US is conveyed through the octopaminergic system and OAMB (Fig.…”

“…1, 2). The subsequent isolation of dopamine (DA) and octopamine (OA) receptor genes and mutants (Han et al 1996Kim et al 2003Kim et al , 2007Kim et al , 2013 along with other reagents allowed this specific hypothesis to be tested (Schwaerzel et al 2003), which produced results consistent with the broad model that the US pathway for aversive conditioning is mediated by G-protein-coupled DA receptors expressed by the MBn and that the US pathway for appetitive conditioning is mediated by both G-protein coupled OA and DA receptors expressed by the MBn (Connolly et al 1996;Schwaerzel et al 2003;Kim et al 2007Kim et al , 2013. The CS and US coincidence integration in the MBn occurs, at least in part, through the activity of an adenylyl cyclase encoded by the rutabaga (rut) gene (Tomchik and Davis 2009).…”

A Drosophila Model of Intellectual Disability Caused by Mutations in the Histone Demethylase KDM5

“…Dysregulated genes required at synapses and in cell-cell communication included genes that encode immunoglobulin domain transmembrane proteins involved in determining the specificity of synaptic connections between neurons and their target cells (Carrillo et al, 2015). Within the G-protein signaling category, notable genes included those required for the production ( Tdc1 , Tdc2 ) and reception ( Oamb , Octbeta3R ) of the neurotransmitter octopamine that is well-established to be necessary for appetitive olfactory short-term learning and memory (Kim et al, 2013). …”

Expression analysis of octopamine and tyramine receptors in Drosophila

“…Most important with regard to this aspect is the Oamb receptor that was named according to its high expression levels in the mushroom bodies (OA receptor primarily expressed in mushroom bodies; Han et al 1998). Recently, it has been shown that Oamb is required for appetitive learning in the fly (Kim et al 2013). A very elegant study revealed the involvement of the Oamb receptor as well as of Octß2R in different aspects of olfactory learning in the fly, indicative of a complex role of octopaminergic signaling in this process (Burke et al 2012).…”