What role do different interneurons in medial prefrontal cortex play in associative recognition memory?

内侧前额叶皮层的不同中间神经元在联想识别记忆中发挥什么作用？

• 批准号: BB/X000915/1
• 负责人: Zafar Bashir
• 金额: $ 86.89万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX000915%2F1
• 关键词: What; role; do; different; interneurons

Associative recognition memory is the process that enables us to form normal, every-day memories. This allows us to remember where we parked the car, where we left our keys, or our phone. This type of memory is essential for us to be able to live our normal lives and underlies some of the first noticeable deficits that occur when cognitive decline or Alzheimer's disease begins to set in. Defining the brain processes which give rise to associative memory is important for understanding how the brain operates under normal conditions but is also important in beginning to understand the mechanisms that start to break down in old age or in Alzheimer's disease. Rodents such as rats and mice also use associative recognition memory in their normal lives, and we have shown that a number of different brain regions including the prefrontal cortex, hippocampus, and regions of the thalamus work together during associative recognition memory. These different regions work together with the prefrontal cortex to control the initial learning and then the remembering of the original memory. However, there are still many things that we don't know about how these brain regions operate. One of the questions we will answer is: how do inhibitory cells in the prefrontal cortex control the function of this brain region during associative memory? We propose that the hippocampus and the nuclei of the thalamus control different types of inhibitory cells in the prefrontal cortex and that the separate activation of the different inhibitory cells by these different brain regions separately brings about the initial encoding and then the retrieval of the memory. We will test these ideas in mice by selectively targeting and silencing the major types of interneurons in prefrontal cortex during different phases of memory. We will use advanced anatomical markers and light microscopy methods to detect whether the hippocampus and the thalamic connections to prefrontal cortex terminate on the different inhibitory cell types. Finally, we will examine how these different connections control activity of the different inhibitory cells and therefore control the function of the prefrontal cortex. The project is timely because we have only recently identified the different regions that work together to bring about the different phases of associative recognition memory and it is now possible to identify and selectively target different inhibitory cells while a mouse is performing a learning task. Furthermore, the anatomical methods have recently been developed that now allow us to identify which brain regions connect with which inhibitory cells and finally we can record from these cells to measure how their activity is controlled by the different brain regions that control associative memory. Overall, this work will provide a detailed mechanistic insight into how brain regions work collectively to bring about associative recognition memory.

关联识别记忆是使我们能够形成正常的每日记忆的过程。这使我们能够记住我们停放汽车的位置，我们留下了钥匙或手机。这种类型的记忆对于我们必须过着正常的生活至关重要，并奠定了一些在认知下降或阿尔茨海默氏病开始介入时出现的第一个明显的缺陷。定义引起缔合记忆的大脑过程很重要，这对于在正常状态下的运作非常重要，但在开始疾病的机制中也很重要，而这也是对年龄较大的机制的开始。大鼠和小鼠等啮齿动物在正常生活中也使用联想识别记忆，我们表明，许多不同的大脑区域，包括前额叶皮层，海马，海马和丘脑的区域在关联识别记忆中共同工作。这些不同的区域与前额叶皮层合作，以控制初始学习，然后再记住原始内存。但是，关于这些大脑区域如何运作，我们仍然有很多事情。我们要回答的问题之一是：前额叶皮层中的抑制细胞如何控制联想记忆期间该大脑区域的功能？我们提出，丘脑的海马和核的核控制着前额叶皮层中的不同类型的抑制细胞，并且这些不同的大脑区域通过这些不同的大脑区域对不同抑制性细胞的单独激活分别带来了初始编码，然后将记忆的检索带来。我们将通过在不同的记忆阶段选择性地靶向和沉默前额叶皮层中主要的中间神经元的主要类型的中间神经元来测试这些想法。我们将使用先进的解剖标记和光显微镜方法来检测海马和丘脑与前额叶皮层的连接是否终止于不同的抑制性细胞类型。最后，我们将研究这些不同的连接如何控制不同抑制性细胞的活性，从而控制前额叶皮层的功能。该项目之所以及时，是因为我们直到最近才识别出共同工作以带来关联识别记忆的不同阶段的不同区域，现在可以在鼠标执行学习任务时识别并有选择地识别并选择性地靶向不同的抑制细胞。此外，最近已经开发出解剖方法，现在使我们能够确定哪个大脑区域与哪些抑制细胞连接，最后我们可以从这些细胞中记录以测量其活性如何由控制关联记忆的不同大脑区域控制。总体而言，这项工作将为大脑区域如何共同发挥关联识别记忆提供详细的机理见解。