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. In this doctoral thesis, I report that robust stress induces a persistent behavioural change characterized by avoidance of a confined space, claustrophobia-like behaviour in Drosophila, which is not associated with specific cues. Unlike aversive memory formation, the development of claustrophobia-like behavior does not require dopamine receptors. 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 reveale...[ Read more ]

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. In this doctoral thesis, I report that robust stress induces a persistent behavioural change characterized by avoidance of a confined space, claustrophobia-like behaviour in Drosophila, which is not associated with specific cues. Unlike aversive memory formation, the development of claustrophobia-like behavior does not require dopamine receptors. 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. These data demonstrate that stress-induced persistent behavioural 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 behavioural modes.