Lipid regulation of synaptic transmission and neuroplasticity

突触是大脑的功能单位，是神经细胞通过称为突触传递的过程相互交流的专门结构。这包括由突触前神经元释放神经递质，并将该神经递质与突触后神经元或肌肉结合。对于我们对神经系统的理解，没有比突触更重要的结构了。突触将信息从一个神经元传递到另一个神经元的能力随着学习和记忆等过程中的经验(突触可塑性)而变化。我用果蝇--黑腹果蝇--来研究突触如何工作和传递信息的基本问题。果蝇突触的功能与包括人类在内的哺乳动物的功能非常相似。因此，我的发现将具有普遍的适用性。这项提案中的工作将解决脂质，特别是胆固醇在突触功能中的作用。脂质是神经系统中含量最丰富的有机化合物之一，在突触中尤其丰富。然而，尽管它们丰富，但脂类在突触如何工作和传递信息中所起的作用直到最近才引起人们的注意。在这项提案中，我们将首先研究胆固醇在突触传递信息的能力中所起的作用。其次，我们将研究突触中胆固醇的组成是否会随着经验的变化而变化，以及这些变化是否是突触可塑性发生所必需的。第三，我们将确定不同突触中胆固醇成分的变化是否会导致释放的神经递质的概率或数量的差异。这项拨款提案的发现将通过确定胆固醇在不同突触的突触功能、可塑性和突触强度变化中的作用，扩大我们对突触功能的了解。

Synapses, the functional units of the brain, are specialized structures where nerve cells communicate with each other through a process called synaptic transmission. This involves the release of neurotransmitter by a presynaptic neuron and binding of this neurotransmitter to a postsynaptic neuron or muscle. No other structures are more fundamental to our understanding of the nervous system than synapses. The ability of a synapse to transmit information from one neuron to another, changes with experience (synaptic plasticity) in processes such as learning and memory. I use the fruit fly, Drosophila melanogaster, to study fundamental questions of how synapses work and transmit information. The way synapses function in the fruit fly are remarkably similar to how they work in mammals, including humans. Thus, my findings will have general applicability. The work in this proposal will address the role of lipids, specifically cholesterol, in synaptic function. Lipids are among the most abundant organic compounds in the nervous system and are particularly enriched at synapses. However, despite their abundance, the part played by lipids in how synapses work and transmit information has only recently gained attention. In this proposal, we will first examine the role cholesterol plays in the ability of synapses to transmit information. Second, we will examine whether the composition of cholesterol at synapses changes with experience and whether these changes are required for synaptic plasticity to occur. Third, we will determine if variation in cholesterol composition in different synapses results in differences in the probability or the amount of neurotransmitter that is released. The findings from this grant proposal will expand our knowledge of how synapses function by determining the role of cholesterol in synaptic function, plasticity and variation in synaptic strength in different synapses.