Memory formation is a continuous process composed of multiple phases that can develop independently from each other. These phases depend on signaling pathways initiated after the activation of receptors in different brain regions. The NMDA receptor acts as a sensor of coincident activity between neural inputs, and, as such, its activation during learning is thought to be crucial for various forms of memory. In this study, we inhibited the expression of the NR1 subunit of the NMDA receptor in the honeybee brain using RNA interference. We show that the disruption of the subunit expression in the mushroom body region of the honeybee brain during and shortly after appetitive learning selectively impaired memory. Although the formation of mid-term memory and early long-term memory was impaired, late long-term memory was left intact. This indicates that late long-term memory formation differs in its dependence on NMDA receptor activity from earlier memory phases.
Memories are classified as consolidated (stable) or labile according to whether they withstand amnestic treatment, or not. In contrast to the general prevalence of this classification, its neuronal and molecular basis is poorly understood. Here, we focused on consolidated and labile memories induced after a single cycle training in the Drosophila aversive olfactory conditioning paradigm and we used mutants to define the impactofcAMPsignals.AtthebiochemicallevelwereportthatcAMPsignalsmisrelatedineither rutabaga(rut)ordunce (
Synaptic vesicle secretion requires the assembly of fusogenic SNARE complexes. Consequently proteins that regulate SNARE complex formation can significantly impact synaptic strength. The SNARE binding protein tomosyn has been shown to potently inhibit exocytosis by sequestering SNARE proteins in nonfusogenic complexes. The tomosyn–SNARE interaction is regulated by protein kinase A (PKA), an enzyme implicated in learning and memory, suggesting tomosyn could be an important effector in PKA-dependent synaptic plasticity. We tested this hypothesis in
Drosophila
, in which the role of the PKA pathway in associative learning has been well established. We first determined that panneuronal tomosyn knockdown by RNAi enhanced synaptic strength at the
Drosophila
larval neuromuscular junction, by increasing the evoked response duration. We next assayed memory performance 3 min (early memory) and 3 h (late memory) after aversive olfactory learning. Whereas early memory was unaffected by tomosyn knockdown, late memory was reduced by 50%. Late memory is a composite of stable and labile components. Further analysis determined that tomosyn was specifically required for the anesthesia-sensitive, labile component, previously shown to require cAMP signaling via PKA in mushroom bodies. Together these data indicate that tomosyn has a conserved role in the regulation of synaptic transmission and provide behavioral evidence that tomosyn is involved in a specific component of late associative memory.
Here, we define a role of the cAMP intermediate EPAC in aversive odor learning by means of null epac mutants. Complementation analysis revealed that EPAC acts downstream from the adenylyl cyclase and in parallel to protein kinase A. By means of targeted knockdown and genetic rescue we identified mushroom body Kenyon cells (KCs) as a necessary and sufficient site of EPAC action. We provide mechanistic insights by analyzing acquisition dynamics and using the "performance increment" as a means to access the trial-based sequential organization of odor learning. Thereby we show that versatile cAMP-dependent mechanisms are engaged within a sequential order that correlate to individual trials of the training session.
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