Fine tuning the nicotinic receptor response via the lipid bilayer

大脑中的神经细胞通过称为突触的连接相互交流。在突触中，小的化学神经递质从一个神经细胞的突触前末端释放出来，与位于另一个神经细胞突触后膜的受体相互作用。与受体结合后，神经递质引发结构变化，导致突触后神经细胞内环境的改变。这种细胞内环境的改变通常导致突触后神经的放电或抑制放电。突触是复杂神经过程的核心。例如，可以通过加强突触来提高记忆力。另一方面，突触传递的改变会导致各种神经系统疾病。因此，理解突触是如何被调节的是理解人类大脑的基础。****我的实验室对神经递质受体感兴趣，称为配体门控离子通道，位于突触后膜上。这些配体门控离子通道的活性可以被多种因素调节，包括尼古丁等外部化合物。我们感兴趣的是了解周围膜中的脂质如何影响功能。使用模型系统，我们将表征在这种环境中发现的脂质，然后测试这些脂质如何影响配体门控离子通道功能。利用复杂的分子生物学、电生理学和晶体学工具，我们将测试脂质改变功能的机制。总体目标是了解在正常和异常神经条件下脂质调节配体门控离子通道功能的作用。这项基础研究将为帮助理解复杂的神经系统疾病，如阿尔茨海默病等提供基础***************

Nerve cells in the brain communicate with each other at connections called synapses. At a synapse, small chemical neurotransmitters are released from the pres-synaptic terminus of one nerve cell to interact with receptors located in the post-synaptic membrane of another nerve cell. Upon binding to a receptor, the neurotransmitter elicits a structural change that leads to alteration of the environment inside the post-synaptic nerve cell. This change in intracellular environment usually leads to either the firing or the inhibition of firing in the post-synaptic nerve. ***Synapses are at the heart of complex neurological processes. For example, synapses can be strengthened to improve memory. On the other hand, altered synaptic transmission can lead to a variety of neurological disorders. Understanding how synapses are modulated is thus fundamental to understanding the human brain.****My lab is interested in the neurotransmitter receptors, called ligand-gated ion channels, that are located in post-synaptic membranes. The activities of these ligand-gated ion channels can be modulated by a variety of factors, including external compounds such as nicotine. We are interested in understanding how the lipids in the surrounding membrane influence function. Using a model system, we will characterize the lipids found in this environment and then test how these lipids influence ligand-gated ion channel function. Using sophisticated molecular biology, electrophysiology, and crystallography tools, we will test proposed mechanisms by which lipids alter function. The overarching goal is to understand the role of lipids modulating ligand-gated ion channel function under both normal and abnormal neurological conditions. This fundamental research will provide a basis to help understand complex neurological diseases, such as Alzheimer's Disease, etc. ***************