Disinhibition-mediated long-term potentiation

动物适应不断变化的环境的能力在很大程度上取决于它们的学习和记忆能力。为了做到这一点，大脑在任何给定时间都要破译数十亿神经元之间的数千个电信号。然而，目前还不清楚这些电信号中包含的哪些信息是大脑认为至关重要的。例如，重要的是神经活动的总量还是两个神经元电活动时间的微小差异？我们的研究不仅集中在研究大脑如何解码电信号，还集中在学习和记忆的细胞和分子机制上。利用最先进的记录技术，我们能够同时测量两个神经元的电活动，这两个神经元被修改以响应模拟学习的电信号。这种神经元对电活动的反应被称为突触可塑性。这项拨款的重点是了解大脑化学物质乙酰胆碱如何改变突触的可塑性。这项研究具有重要的临床意义，因为阿尔茨海默病是一种神经退行性疾病，会导致严重的记忆障碍，其原因是大脑中乙酰胆碱的丧失。通过对成年啮齿动物的海马组织进行实验，我们可以确定乙酰胆碱如何影响突触可塑性的诱导，而突触可塑性是学习和记忆的基础。

The ability of animals to adapt to their ever-changing environments depends in large part on their ability to learn and remember. To do so the brain deciphers thousands of electrical signals between billions of neurons at any given time. However it is unclear what information contained within these electrical signals the brain deems critical. For example, is it the overall amount of neural activity that is important or is it the small differences in timing between when two neurons are electrically active? Our research is centered on examining not only how the brain decodes electrical signals, but on the cellular and molecular mechanisms underlying learning and memory. Using state-of-the-art recordings we are able to measure the electrical activity simultaneously from two neurons which are being modified in response to electrical signals that simulate learning. This neuronal modification in response to electrical activity is called synaptic plasticity. This grant is focused on understanding how the brain chemical acetylcholine modifies synaptic plasticity. This research is clinically important because Alzheimer's disease, the neurodegenerative disorder which produces severe memory impairments results from a loss of acetylcholine in the brain. By performing experiments on hippocampal tissue from adult rodents we can determine how acetylcholine affects the induction of synaptic plasticity, which is known to underlie learning and memory.