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

Project Information

ASTROTAMY

Grant agreement ID: 334455

Project closed

Start date 1 October 2013

End date 30 September 2017

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 100 000,00

EU contribution € 100 000,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Final Report Summary - ASTROTAMY (Involvement of astrocyte-neuron interactions in the endogenous oxytocin modification of amygdala microcircuits and the emotional aspects of pain.)

State of the art
Pain is defined by the IASP 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. The amygdala has been identified as a key target nucleus involved in both anxiety and emotional aspect of pain feelings. The central amygdala (CeA) is particularly important for the modulation of the outputs to the brainstem. Thus, understanding of the CeA circuits and how they gate information through involvement of different cells subtypes may therefore provide important perspectives for the treatment of emotional-associated disorders. Importantly, it has recently been discovered how certain endogenous neuropeptides can efficiently regulate the CeA microcircuit. Oxytocin (OT) is a nonapeptide synthesized in the hypothalamus. Interestingly, previous work revealed that OT can modulate CeA activity but it must be noted that the precise localization of OTR is actually unknown, but strong arguments are in favor of their presence in forebrain astrocytes. The present project aims to characterize the involvement of astrocytes in the effects of OT release in the CeA.

Scientific progress and results
In the course of this project we determined the cellular localization of OT receptors (OTR) in a subpopulation of astrocytes in the CeL. Then, we characterized ex vivo the effect of OTR activation on CeL astrocytes, both using confocal calcium imaging and electrophysiology. Next, we demonstrated the primordial role of CeL astrocytes in the OT modulation of CeA microcircuits. Finally, we showed the contribution of CeL astrocytes to the behavioral effect of OT on both pain and anxiety. In conclusion, this study paves the way to a better understanding of OT functions integrations and open a new perspective on the role of astrocytes for neuropeptidergic transmission.