Abdalla G. Alia

Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety or phobia are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior (CLB) in Drosophila . Unlike aversive memory formation, the development of CLB does not require dopamine receptors. Our neuronal screening determined that neuropeptide signaling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing CLB. Moreover, gene expression profiling of individual fly heads revealed that innate immune response activation in the blood–brain barrier is involved in CLB. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signaling and the blood–brain barrier, providing the mechanism determining internal states which persistently change into a phobia-like mode.

Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior in Drosophila . Unlike aversive memory formation, the development of claustrophobia-like behavior does not require dopamine receptors. Our neuronal screening determined that neuropeptide signalling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing claustrophobia-like behavior. Moreover, gene expression profiling of individual fly heads revealed that immune response activation in perineurial barrier is involved in claustrophobia-like behavior. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signalling and perineurial barrier, providing the mechanism determining internal states which persistently change behavioral modes.

Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces memory formation, here we report that cyclic guanine monophosphate (cGMP) signaling via dopamine neurons launches forgetting of unconsolidated memory in Drosophila . Genetic screening and proteomic analyses showed that neural activation induces the complex formation of a histone H3K9 demethylase, Kdm4B, and a GMP synthetase, Bur, which is necessary and sufficient for forgetting unconsolidated memory. Kdm4B/Bur is activated by phosphorylation through NO-dependent cGMP signaling via dopamine neurons, inducing gene expression, including kek2 encoding a presynaptic protein. Accordingly, Kdm4B/Bur activation induced presynaptic changes. Our data demonstrate a link between cGMP signaling and synapses via gene expression in forgetting, suggesting that the opposing functions of memory are orchestrated by distinct signaling via dopamine neurons, which affects synaptic integrity and thus balances animal behavior.

[This corrects the article DOI: 10.1155/2016/1089364.].