YTANIZAWA · Dissecting dynamic monoaminergic nervous system in C. elegans with genetically-encoded neuron activator protein channelrhodopsin-2.
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2008-06-01 → 2010-05-31
- Финансиране от ЕС
- 178 874 €
- Участници
- 1
- Схема
- MC-IIF
Линиите свързват координатора с партньорите.
Накратко на български
Нервната система на червея C. elegans се анализира чрез комбиниране на механични стимули и светлинна активация на неврони. Това помага да се разбере как различните сетивни сигнали взаимодействат помежду си и променят нивото на възбудимост на организма.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Dissecting dynamic monoaminergic nervous system in c. elegans with genetically-encoded neuron activator protein channelrhodopsin-2
The nervous system of the nematode c. elegans, a tiny worm which is around 1 mm long, consists of 302 neurons which were described by electron microscopic observation along with all the synaptic connections. The latter description included approximately 7 000 chemical and 700 electrical synapses. Despite the simplicity of their nervous system, worms can sense and respond to various sensory stimuli including taste, odour, temperature, ultraviolet (UV) light and mechanical stimuli. Ease of genetic manipulation and its transparent body rendered it possible to control and monitor activity of specific neurons in vivo with genetically encoded tools. Finally, a huge repository of mutants allowed us to examine the roles of genes in the nervous system. These characteristics were anticipated to make c. elegans a satisfactory model to study multisensory processing in its simplest form at multiple levels, ranging from gene to behaviour. Using c. elegans as a model we studied how sensory stimuli in different modalities interacted with each other in the nervous system. We utilised two stimuli as sensory inputs, namely actual mechanical stimuli to body and artificial activation of nociceptive neurons with light-gated ion channel channelrhodopsin-2, allowing for precise control of stimulus strength and location. The analysis of behavioural, i.e. withdrawal, response to these inputs had so far indicated no sign of additive effect when the two inputs were presented simultaneously. However, when interval was given between the two stimuli, significant enhancement of response to the second stimulus with enhanced motor activity was observed. This result indicated the existence of an 'arousal' change in the worm nervous system, which was also important for understanding indirect interaction among different modalities. By screening available mutants we also found that neuropeptide signalling played a role in arousal modulation. By the time of the project completion, we were trying to measure the activity of neurons in behaving worms using genetically-encoded activity sensors, in order to understand where and how this change occurred at cellular level. In addition, activity monitoring could possibly identify multisensory integration effect at cellular level even though this was not previously behaviourally identified. We also planned to use stimuli in other modalities to discover novel interactions amongst them in multisensory integration and arousal modulation.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Biogenic monoamines are relevant to influential psychological diseases and brain plasicity. Knowledge obtained so far is however not enough for both of scientific and medical purposes. One obstacle against proceeding is the difficulty to find novel genes in genetically-inaccessible system like human brain. Another problem is the complexity of brain making it difficult to link cellular phenomena to behavior, which is necessary to understand brain. To solve these problems, a genetically-accessible model organism C. elegans was introduced. With only 302 neurons, nervous system of C. elegans still has many properties common to the higher animal’s brain, including usage of monoamines and their roles in neural plasticity. Studies so far in C. elegans have provided much information by using mutants, exogenous amine application and neuron ablation. However, these methods have not considered dynamic property of aminergic system. Here, the applicant uses the genetically-encoded light-gated cation channel channelrhodopsin-2 (ChR2). Because the body of C. elegans is transparent, by expressing and light-activating ChR2 specifically in aminergic neurons, one can examine the amine effectss on behavior with precise time resolution. The automated behavior quantification system makes it possible to identify any subtle behavioral changes caused by aminergic activation. The applicant will also examine the amine effects in cellular level, by live-imaging of downstream neuron activity with sensor protein cameleon. After identifying the amine effects, the applicant will start to dissect aminergic system with powerful genetics of C. elegans, which will provide a good starting point for further studies in future. This project for the first time allows us to examine the dynamic aspects of genetically-dissectable aminergic system, so it will contribute much to understanding aminergic system and also to European excellence in this promising and competitive field of C. elegans neurobiology.
Оригинален текст от CORDIS (на английски).
Участници
- MEDICAL RESEARCH COUNCIL · LONDONКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз