Synaptic depression induced by postsynaptic cAMP production in the <i>Drosophila</i> mushroom body calyx

<jats:sec><jats:title>Key points</jats:title><jats:p><jats:list list-type="bullet"> <jats:list-item><jats:p>Synaptic potentiation in <jats:italic>Drosophila</jats:italic> is observed at cholinergic synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult brain; however, depression at the AL–MB synapses has not yet been identified.</jats:p></jats:list-item> <jats:list-item><jats:p>By <jats:italic>ex vivo</jats:italic> Ca<jats:sup>2+</jats:sup> imaging in an isolated cultured <jats:italic>Drosophila</jats:italic> brain, we found novel activity‐dependent depression at the AL–MB synapses.</jats:p></jats:list-item> <jats:list-item><jats:p>The degree of Ca<jats:sup>2+</jats:sup> responses after repetitive AL stimulation is significantly reduced in the dendritic region of MB neurons (calyx) compared with those before AL stimulation, and this reduction of Ca<jats:sup>2+</jats:sup> responses remains for at least 30 min.</jats:p></jats:list-item> <jats:list-item><jats:p>The expression of <jats:italic>rutabaga</jats:italic>, which encodes Ca<jats:sup>2+</jats:sup>/calmodulin‐dependent adenylyl cyclase, is essential in the MB neurons for the reduction of Ca<jats:sup>2+</jats:sup> responses in the calyx.</jats:p></jats:list-item> <jats:list-item><jats:p>Our study reveals that elevation of cAMP production in the calyx during repetitive AL stimulation induces the depression at the AL–MB synapses.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec><jats:sec><jats:title>Abstract</jats:title><jats:p>Synaptic plasticity has been studied to reveal the molecular and cellular mechanisms of associative and non‐associative learning. The fruit fly <jats:italic>Drosophila melanogaster</jats:italic> can be used to identify the molecular mechanisms of synaptic plasticity because vast genetic information or tools are available. Here, by <jats:italic>ex vivo</jats:italic> Ca<jats:sup>2+</jats:sup> imaging of an isolated cultured <jats:italic>Drosophila</jats:italic> brain, we examined the novel activity‐dependent synaptic depression between the projection neurons of the antennal lobe (AL) and mushroom body (MB). <jats:italic>Ex vivo</jats:italic> Ca<jats:sup>2+</jats:sup> imaging analysis revealed that electrical stimulation of AL elicits Ca<jats:sup>2+</jats:sup> responses in the dendritic (calyx) and axonal (α lobe) regions of MB neurons, and the responses are reduced after repetitive AL stimulation. Since the cAMP signalling pathway plays an important role in synaptic plasticity in invertebrates and vertebrates, we examined whether the reduction of Ca<jats:sup>2+</jats:sup> responses is also regulated by the cAMP signalling pathway. The expression of <jats:italic>rutabaga</jats:italic> (<jats:italic>rut</jats:italic>), which encodes Ca<jats:sup>2+</jats:sup>/calmodulin‐dependent adenylyl cyclase, was essential for the reduction of Ca<jats:sup>2+</jats:sup> responses in the calyx and α lobe. Furthermore, imaging analysis using a fluorescence resonance energy transfer‐based cAMP indicator revealed that the cAMP level increased in the wild‐type calyx during repetitive AL stimulation, whereas it decreased in <jats:italic>rut<jats:sup>1</jats:sup></jats:italic>mutant flies with a loss‐of‐function mutation of <jats:italic>rut</jats:italic>. Thus, our study suggests that an increase in postsynaptic cAMP level during repetitive AL stimulation contributes to the attenuation of inputs at AL–MB synapses.</jats:p></jats:sec>