The Neuromodulatory Landscape of Honey Bee Cognition: Roles of Acetylcholine, Glutamate, GABA, and Biogenic Amines

Honey bees ( Apis mellifera) have emerged as a powerful model organism for studying the neurobiology of learning and memory. Research in the past decade highlights that multiple neurotransmitter systems contribute to different phases and forms of memory in the honey bee brain. Acetylcholine (ACh) is the primary excitatory transmitter in insect neural circuits, playing key roles in the acquisition and retrieval of learned associations. Glutamatergic signaling, although less prevalent than in vertebrates, is essential for certain memory processes, involving both ionotropic (e.g. NMDA-type) and metabotropic pathways. Inhibitory neurotransmission via γ-amino-butyric acid (GABA) shapes olfactory learning by gating and refining neural activity, enabling cognitive flexibility. Biogenic amines act as critical neuromodulators: dopamine and octopamine provide aversive and appetitive reinforcement signals, respectively, during associative learning, while recent findings also implicate dopamine in appetitive motivation (“wanting”). This review synthesizes current knowledge on these neurotransmitter systems at both molecular and systems levels in the honey bee, illustrating how a complex interplay of signaling molecules underlies learning and memory. We conclude with an overview of how these neuromodulatory pathways integrate to support the sophisticated cognitive capacities of honey bees, and point to open questions for future research.