Modulation of aversive value coding by previous nociceptive experience in Drosophila.

• Applicant: Carlotta Martelli, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545515202

Previous painful/nociceptive experience modulates the way animals perceive and react to future harmful or threat-predicting cues. Yet our understanding of how nociceptive stimuli are perceived, integrated, modulated by previous experience, and evaluated in the brain remain poorly understood. This is of particular importance to comprehend the decision mechanisms that allow animals to make the most appropriate choices. Nociceptive stimuli are detected by nociceptors in the periphery and relayed to the central brain via ascending neurons. This nociceptive information reaches many brain regions including dopaminergic circuits that signal aversive value during associative learning. In addition, painful/nociceptive experiences can trigger stress signals inducing analgesia that modulates how future nociceptive stimuli are processed in the central nervous system. However, the circuits and mechanisms for stress-dependent modulation of nociception remain elusive. As basic mechanisms of nociceptive perception and modulation are conserved across phyla, the NOCIFLY proposal takes advantage of a genetic model system, Drosophila, and state-of-the-art multilevel approaches to shed light on the neural mechanisms that mediate nociceptive perception, stress-induced analgesia and their role in nocifensive behaviour and aversive learning. Combining high-throughput and high-resolution behavioural approaches (Perisse lab) with state of the art anatomical and physiological approaches (Martelli lab), NOCIFLY Aim 1 is to characterise detailed nocifensive behaviour and to identify fly nociceptors and nociceptive ascending pathways that relay nociceptive stimuli to dopaminergic circuits. In Aim 2, NOCIFLY will identify key components of Drosophila stress odours (dSO) to investigate how they modulate nocifensive behaviour (Perisse lab), and to characterise their neural representation (Martelli lab). Finally, in Aim 3, NOCIFLY will assess the role of stress signals in modulating odour processing (Martelli lab) in the context of an aversive learning assay (Perisse lab), with the goal of understanding the mechanisms that allow animals to compare aversive options for appropriate behaviours. The proposed work programme will provide the first full characterization of multimodal nociceptive perception and integration of nociceptive signals to dopaminergic circuits, as well as a comprehensive overview of how stress signals affect nociception and aversive learning.

• DFG Programme: Research Grants
• International Connection: France
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Dr. Emmanuel Perisse