ASTROTAMY · Involvement of astrocyte-neuron interactions in the endogenous oxytocin modification of amygdala microcircuits and the emotional aspects of pain

Pain and anxiety disorders are taking a large toll in our society both in loss of productivity and total cost of healthcare. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. This definition highlights the complexity and the subjective character of such a sensation as well as one of its major aspects: the emotional component of pain. Neuroscience research has identified the amygdala as a key target nucleus in the brain that is involved in both anxiety and pain feeling. Amygdala is thus considered as the basis of the autonomous, behavioural and emotional integrated response to pain.The present project aims to characterize in vitro and in vivo involvement of astrocytes in the effects of endogenous oxytocin (OT) release in the amygdala microcircuitry. For this purpose, channelrhodopsin-2 (ChR-2) will be expressed under the OT promoter in order to induce release from OT containing fibers in the amygdala by blue light exposure. In vivo effects will be assessed on both naive and neuropathic animals through a functional exploration of pain i) symptomatic (nociceptive and anxiety tests) and ii) physiologic (radiotelemetry and behaviour). In vitro effects will be measured using i) patch clamp recordings of central amygdala neurons after astrocytes inactivation and ii) confocal cell-live calcium imaging in horizontal rat brain slices. Finally, the cellular localization of the OT receptor will be determined by i) in situ hybridization and ii) RT-PCR.The results of this project will contribute to the comprehension of the mechanisms behind the emotional impacts of a chronic pain. Moreover, a better understanding of the mechanisms of action of neuropeptides as well as the evaluation of new potent therapeutic target will contribute to the elaboration of new human and veterinary clinical use.""