Input-timing-dependent plasticity at incoming synapses of the mushroom body facilitates olfactory learning in Drosophila

Aversive olfactory conditioning in Drosophila is a valuable model for elucidating the mechanism of associative learning. Much effort has centered around the role of neuroplasticity at the mushroom body (MB)-mushroom body output neuron (MBON) synapses in mapping odors to specific behaviors. By electrophysiological recordings from MB neurons, we discovered a form of input-timing-dependent plasticity at the incoming synapses from projection neurons that controls the efficacy of aversive olfactory memory formation. Importantly, this plasticity is facilitated by the neural activity of PPL1, the neuronal cluster that also modulates MB-MBON connections at the output stage of MB. Unlike the MB-MBON synapses that probably utilize dopamine D1-like receptors, this neuroplasticity is dependent on D2-like receptors that are expressed mainly by γ Kenyon cells noticeably in their somato-dendritic region. The D2-like receptors recruit voltage-gated calcium channels, leading to calcium influx in the soma and dendrites of γ neurons. Together, our results reveal a previously unrecognized synaptic component of the MB circuit architecture that not only could increase the salience of a conditioning odor but also couples the process of memory encoding and valency mapping to drive-associative learning. © 2022 Elsevier Inc.