Homeostatic active zone remodeling consolidates memories in the Drosophila mushroom body

Establishing a detailed understanding of how the distinct forms of synaptic plasticity spatio-temporally engage into the initial storage and subsequent consolidation of memories remains a fundamental challenge of neuroscience. In addition to the better understood postsynaptic plasticity, different forms of presynaptic plasticity are widely expressed in mammalian brains and apparently operate along Hebbian or homeostatic rules. Their behavioral relevance remains enigmatic, however. Lately, acute upregulation of active zone (AZ) scaffold protein BRP and release factor Unc13A via specific axonal transport factors were shown to mediate stable expression of presynaptic homeostatic plasticity (PHP) at Drosophila neuromuscular junctions (NMJs). We here demonstrate that AZ scaling processes are specifically needed for stable expression of both, NMJ PHP as well as aversive olfactory mid-term memory within intrinsic neurons of the Drosophila mushroom body (MB). We first demonstrate that AZ upscaling via BRP is specifically needed for expression but not induction of NMJ homeostatic plasticity, thus establishing a direct temporal plasticity sequence of molecularly distinct AZ remodeling steps. Notably, when we reduced BRP and associated transport factors in MB intrinsic neurons, short-term memory persisted but robust deficits in stable memory expression for a few hours after conditioning were observed. In contrast, AZ release site protein RIM-BP affecting PHP induction was additionally needed for successful formation of short-term memory. Taken together, our data establish a specific role of homeostatic presynaptic long-term plasticity for memory consolidation. Such homeostatic refinement processes might well be needed to successfully integrate and display synaptic engrams constituting intermediary term memories.