Pairing-Dependent Plasticity in a Dissected Fly Brain Is Input-Specific and Requires Synaptic CaMKII Enrichment and Nighttime Sleep

Abstract

InDrosophila,in vivofunctional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require anex vivomodel that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The currentex vivomodels have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neuron (Kenyon cells [KCs]) responses after artificial learningex vivo. However, this potentiation showed different localization and encoding properties from those reportedin vivoand failed to generate the previously reported suppression plasticity in the MB output neurons (MBONs). Here, we develop anex vivomodel using the femaleDrosophilabrain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB α′3 compartment and is encoded by a coincidence between KC activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus and unconditioned stimulus pathways; hence, we name it pairing-dependent plasticity. Pairing-dependent plasticity formation requires an intactCaMKIIgene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that ourex vivopreparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state.SIGNIFICANCE STATEMENTThe mammalianex vivoLTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study theDrosophilamushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of α′β′ Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB α′3 compartment. This PDP is input-specific and requires the 3′ untranslated region ofCaMKII. Interestingly,ex vivoPDP carries information about the animal's experience before dissection; brains from sleep-deprived animals fail to form PDP, whereas those from animals who recovered 2 h of their lost sleep form PDP.