ASTROTAMY · Involvement of astrocyte-neuron interactions in the endogenous oxytocin modification of amygdala microcircuits and the emotional aspects of pain
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-10-01 → 2017-09-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Взаимодействието между астроцитите и невроните в амигдалата се проучва чрез влиянието на окситоцина върху емоционалните аспекти на болката. Разбирането на тези процеси помага при търсенето на методи за лечение на разстройства, свързани с емоциите.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.""
Оригинален текст от CORDIS (на английски).
Участници
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз