Optical activation of a C. elegans neural circuit underpinning feeding behaviour

神经元之间的交流是大脑功能的一个基本方面。这是由化学神经递质介导的，这些神经递质在神经细胞上被称为突触的特定位置从一个神经细胞传递到另一个神经细胞。人类大脑中有数万亿个这样的突触，它们的正确功能对良好的心理健康至关重要。这种突触通讯的功能障碍是大多数精神和神经退行性疾病的基础，包括抑郁症、焦虑症、精神分裂症、帕金森病、阿尔茨海默病和许多其他流行和痛苦的疾病。事实上，许多用于治疗这些疾病的药物都是通过改善突触通讯来改善疾病症状的。然而，在许多情况下，这些药物是相当“钝的工具”。一个主要的问题是，化学神经传递是复杂的，而且非常具有可塑性。人们对其微妙之处的理解仍然相对肤浅。具体来说，任何给定的突触都会储存大量的神经递质，这些递质可以根据神经细胞的活动以不同的比例释放，从而产生突触“鸡尾酒”。不同的“鸡尾酒”对突触的信号传递有不同的影响。很明显，突触“调制鸡尾酒”并改变其信号特性的能力与神经元回路的能力有关，最终与大脑改变其输出和行为的能力有关。因此，神经科学的一个基本目标是了解不同种类的神经递质在神经元回路中的作用，以及信号的改变如何导致行为的改变。这是一个复杂的问题，许多神经科学家，包括我们自己，都选择研究简单的无脊椎动物神经系统来解决这个问题。我们选择的模型，秀丽隐杆线虫的优势在于，尽管它有一个非常简单的神经系统，只有5000个突触，而不是数万亿个，但它有和人类一样复杂的神经细胞间信号传递机制。此外，动物表现出简单的行为，并会根据其环境以适当的方式适应。这表明它有能力像高等动物一样重新配置自己的神经回路。这个模型系统的吸引力在于，它很容易从基因水平到分子、神经元、电路和完整行为的动物研究一个特定的问题。我们正在研究的行为是动物对食物剥夺的反应。在这里，我们正在利用一项新的技术进步，使我们能够激活调节这种适应性反应和记录突触信号的神经元回路的特定元素。通过对不同的基因突变体进行分析，我们将能够定义电路中信号的特性，并描述与动物行为变化平行的信号变化。这将为改变突触信号如何导致行为改变的基本问题提供独特的见解，并为进一步对该问题进行遗传分析铺平道路。

Communication between neurones is a fundamental aspect of brain function. This is mediated by chemical neurotransmitters that signal from one nerve cell to the next at specific sites on the nerve cell called synapses. There are trillions of these synapses in the human brain and their correct function is essential for good mental health. Dysfunction in this synaptic communication is the basis for the majority of psychiatric and neurodegenerative disorders including depression, anxiety, schizophrenia, Parkinson's disease, Alzheimer's disease and many other prevalent and distressing conditions. Indeed, many of the drugs used to treat these disorders act to improve synaptic communication to ameliorate the symptoms of the disease. However in many cases these drugs are fairly 'blunt instruments'. A major problem is that chemical neurotransmission is complex and also very plastic. There is still a relatively superficial understanding of its subtleties. Specifically, any given synapse will store a multitude of neurotransmitters which can be released in different proportions depending on the activity of the nerve cell giving rise to a synaptic 'cocktail'. Different 'cocktails' have different consequences for signalling at the synapse. It is clear that the ability of the synapse to 'mix a cocktail' and alter its signalling properties is related to the ability of the neuronal circuits, and ultimately the brain, to alter its output and change behaviour. Therefore a fundamental goal of neuroscience is to understand the role of distinct classes of neurotransmitters within neuronal circuits and how altered signalling leads to a change in behaviour. This is a complex problem and many neuroscientists, including ourselves, have chosen to work on simple invertebrate nervous systems to address it. The advantage of the model that we have chosen, the nematode worm C. elegans, is that although it has a very simple nervous system with only 5000 synapses rather than trillions, it has the same complex mechanism for signalling between nerve cells as humans. Furthermore, the animal exhibits simple behaviours and will adapt in an appropriate way according to its environment. This indicates that it has the capacity to re-configure its neural circuits in much the same way as higher animals. The attraction of this as a model system is that it is easy to study a specific problem from the level of the gene through to the molecule, neurone, circuit and the intact behaving animal. The behaviour we are investigating is the response of the animal to food deprivation. Here we are taking advantage of a new technical advance that will enable us to activate specific elements of the neuronal circuit that regulates this adaptive response and record synaptic signalling. By performing this analysis in different genetic mutants we will be able to define the properties of the signal in a circuit and describe changes in the signal that parallel the change in the behaviour of the animal. This will provide a unique insight in to the fundamental problem of how altered synaptic signalling leads to a change in behaviour and pave the way for further genetic analysis of this problem.