Behavior varies even among genetically identical animals raised in the same environment. However, little is known about the circuit or anatomical origins of this individuality. Here, we demonstrate a neural correlate of Drosophila odor preference behavior in the olfactory sensory periphery. Namely, idiosyncratic calcium responses in projection neuron (PN) dendrites and densities of the presynaptic protein Bruchpilot in olfactory receptor neuron (ORN) axon terminals correlate with individual preferences in a choice between two aversive odorants. The ORN-PN synapse appears to be a locus of individuality where microscale variation gives rise to idiosyncratic behavior. Simulating microscale stochasticity in ORN-PN synapses of a 3062 neuron model of the antennal lobe recapitulates patterns of variation in PN calcium responses matching experiments. Conversely, stochasticity in other compartments of this circuit does not recapitulate those patterns. Our results demonstrate how physiological and microscale structural circuit variations can give rise to individual behavior, even when genetics and environment are held constant.

The reward and novelty-related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein-synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesised proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzosko et al., 2015) or postsynaptic burst activation (Fuchsberger et al., 2022). Here, we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP), which is mediated via the Ca²⁺-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis. Furthermore, dopamine induced a protein-synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP.