Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory

Abstract

Efficient energy use has constrained the evolution of nervous systems. However, it is unresolved whether energy metabolism may resultantly regulate major brain functions. Our observation that Drosophila flies double their sucrose intake at an early stage of long-term memory formation initiated the investigation of how energy metabolism intervenes in this process. Cellular-resolution imaging of energy metabolism reveals a concurrent elevation of energy consumption in neurons of the mushroom body, the fly's major memory centre. Strikingly, upregulation of mushroom body energy flux is both necessary and sufficient to drive long-term memory formation. This effect is triggered by a specific pair of dopaminergic neurons afferent to the mushroom bodies, via the D5-like DAMB dopamine receptor. Hence, dopamine signalling mediates an energy switch in the mushroom body that controls long-term memory encoding. Our data thus point to an instructional role for energy flux in the execution of demanding higher brain functions.

Biogenic amines and activity levels alter the neural energetic response to aggressive social cues in the honey bee Apis mellifera

“…Certain classes of dopaminergic neurons are highly metabolically active (Pacelli et al, ), and plasticity in mitochondrial energetics in dopaminergic neurons has been linked to learning and memory processes in Drosophila melanogaster . In this context, dopamine signaling induces a high‐energy state in mushroom body neurons through the receptor DAMB (Placais et al, ). Our data suggest that the combination of dopamine treatment and alarm pheromone exposure could enhance signaling through a similar mechanism.…”

“…Reduced brain energy metabolism, particularly a decline in mitochondrial bioenergetics, plays a major mechanistic role in age, injury, and disease‐related cognitive decline (Alzheimer's Association, ; Swerdlow, Burns, & Khan, ; Yin, Jiang, & Cadenas, ). However, the healthy brain is also characterized by highly dynamic mitochondrial activity (Chan, Black, Lin, Ping, & Lau, ; Pandya, Royland, MacPhail, Sullivan, & Kodavanti, ; Picard & McEwen, ; Shannon et al, ; Vaishnavi et al, ), which allows it to redirect energy to areas of need (Placais et al, ) and balance ATP production with other functions of metabolic pathways, for example, calcium buffering and redox signaling (Maalouf, Sullivan, Davis, Kim, & Rho, ; Pandya, Nukala, & Sullivan, ; Wang, Murray, Chung, & Van Eyk, ; Wang et al, ). Plasticity in neural energetics, which directly impacts signaling, plays an important but understudied role in the regulation of learning, memory, and behavior in healthy animals (Hollis et al, ; Rittschof, Grozinger, & Robinson, ; Rittschof & Schirmeier, ).…”

Neuronal lactate levels depend on glia‐derived lactate during high brain activity in Drosophila

“…There is emerging evidence pointing to an important role of monocarboxylate transport and metabolism in brain function and survival of Drosophila (Liu et al, ; Placais et al, ; Volkenhoff et al, ). However, there is still much debate about their essential role in vivo.…”

“…Using such sensors in Drosophila , it was shown that glucose is quickly and freely distributed between glial and neuronal cells by transporters not yet identified (Volkenhoff, Hirrlinger, Kappel, Klambt, & Schirmeier, ). In addition, another study showed that an increase in energy flux into neurons comprising the mushroom body in the Drosophila adult brain (the center associated with memory and learning in insects) precedes and drives long‐term memory formation (Placais et al, ). The source and nature of the molecules driving the increased energy consumption could not be established due to the limited information about the fluxes of energy‐rich molecules in the Drosophila brain.…”

Initiated by CREB: Resolving Gene Regulatory Programs in Learning and Memory

“…The consolidation of memory to stable and long‐lasting memories is a tightly regulated multistep process. The consolidation of LTM is very energy‐intensive process, requiring protein biosynthesis . Therefore, memory storage only occurs in favorable conditions.…”