5HT-DREADD · In vivo pharmacogenetic investigation of 5-HT mechanisms in emotional learning
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2016-07-01 → 2018-06-30
- Финансиране от ЕС
- 183 455 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите на серотонина в мозъка се проучват чрез специални рецептори, за да се види как те влияят върху паметта за неприятни преживявания. Това помага за разбирането на процесите, които водят до развитието на тревожност и депресия.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
In vivo pharmacogenetic investigation of 5-HT mechanisms in emotional learning
Serotonin is critical for mood regulation in health and disease and strongly implicated in the vulnerability to anxiety and depression. Importantly, accumulating evidence suggests that the main influence of serotonin is upon emotional learning rather than on mood directly. The objective of this project was to determine the neural mechanisms through which changes in serotonin levels, within defined neuronal circuits, affect learning and memory for aversive emotional experiences. However, the neuronal circuitry involved and how serotonin activity translates into behaviour are yet to be fully elucidated. To explore the effect of specifically manipulating serotonin circuitry on emotionality, I have utilised a chemogenetic approach. This involves inserting new genetic code into certain neurons that leads to the expression of new receptors only in those specific cells. These receptors do not respond to any chemical in the brain but instead are only activated by a drug I then deliver weeks later. These are therefore called DREADDs; Designer Receptors Exclusively Activated by Designer Drugs. In this project, I introduced these receptors to serotonin cells in the dorsal raphe nucleus (DRN), the key source of serotonin innervation in the brain. However, these are not the only cells in that area as they are controlled by local inhibitory gamma aminobutyric acid (GABA) neurons. I therefore also explored how expressing these receptors and selectively activating these local GABA neurons affected the functionality of the serotonin system and the subsequent effect on behaviour. This selectivity is achieved by delivering the new genetic code to the DRN with viruses containing the information for these receptors (hM3Dq) as well as a fluorescent “tag”, or just this “tag” (mCherry) to act as a control. Different lines of mice then allow for this to either be expressed only in serotonin neurons (SERT-Cre mice) or the GABA neurons (vGAT-Cre mice).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Emotional health and well-being is widely accepted to be crucial for healthy life and the success of societies. Anxiety and depression are two common and debilitating emotional disorders, with highly negative social and financial implications. Serotonin (5-hydroxytryptamine; 5-HT) is thought to be critical to the healthy mood regulation and strongly implicated in the vulnerability to anxiety and depression. Importantly, accumulating evidence suggests that 5-HT’s main influence is upon emotional learning rather than on mood directly. The objective of this proposal is to determine the neural mechanisms through which changes in 5-HT levels, within defined neuronal circuits, affect learning and memory for aversive emotional experiences. New pharmacogenetic techniques will be developed that allow the selective triggering of 5-HT neuron activation and then inhibition in the same animal. We will use this technology to stimulate or inhibit 5-HT release in the basolateral amygdala, a brain area that is crucial for aversive learning, whilst an animal is engaged in an emotional processing task. Through this we will learn how 5-HT modulates neuronal activity in the amygdala at critical time-points during the encoding and retrieval of aversive memories. The results from these studies will provide entirely new insights into how 5-HT modulates amygdala information processing and aversive learning. Understanding how 5-HT affects emotional learning will ultimately lead to a deeper understanding of healthy mood states and the biological mechanisms underlying vulnerability to disorders such as anxiety and depression.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз