Reconsolidation as a mechanism for the homeostatic regulation of synaptic strength

在大脑和脊髓中，信息通过称为突触的连接在神经细胞之间传递，突触在功能上连接神经细胞，并作为化学交流的关键点。通过改变两个神经细胞的连接程度，可以改变这些细胞之间的信息流。改变神经细胞之间连接强度的能力是神经系统的一种基本属性，称为可塑性。这些突触强度的可塑性变化被认为是记忆和学习的基石。 重要的是，神经细胞之间的可塑性变化不一定是永久性的，可以通过不断激活突触连接来改变。突触可塑性的这一有趣特性允许记忆在被回忆后进行修改。由回忆独特地触发的一种特定形式的记忆修改被称为“记忆再巩固”。记忆再巩固可以在某些条件下更新、加强、甚至擦除记忆痕迹。然而，对于再巩固如何在细胞间突触连接的水平上发挥作用，人们知之甚少。 这项研究计划探索再巩固如何影响神经细胞之间突触连接的强度。我们试图了解重新巩固可以导致神经连通性中可塑性变化的修改和消除的机制，以及这一过程如何受到先前和正在进行的神经活动的调节。我们将结合先进的技术手段直接研究神经细胞之间的化学联系，并使用先进的遗传学方法选择性地激活和研究单个神经细胞中突触的再巩固。此外，我们还将识别能够进行再巩固以消除记忆痕迹的关键蛋白质，目的是操纵这些蛋白质以更好地了解再巩固是如何激活的。 总体而言，这些结果将极大地增强我们对大脑和脊髓中信息流是如何调节的理解。对突触如何激活再巩固以及它如何调节突触强度的研究将对神经元网络如何存储、获取和更新信息产生新的见解。

In the brain and spinal cord, information is passed between nerve cells through connections called synapses that functionally join nerve cells and serve as key points for chemical communication. The flow of information between these cells can be changed by changing how strongly connected two nerve cells are. The ability to change the strength of connections between nerve cells is a fundamental property of the nervous system called plasticity. These plastic changes in synaptic strength are thought to form the building blocks of memory and learning. Importantly, plastic changes between nerve cells are not necessarily permanent, and can be changed by ongoing activation of the synaptic connections. This interesting property of synaptic plasticity allows for the modification of memories after they are recalled. One particular form of memory modification that is uniquely triggered by the recall of a memory is called “memory reconsolidation”. Memory reconsolidation can allow the updating, strengthening, or even the erasure of memory traces under certain conditions. However, very little is known about how reconsolidation functions at the level of synaptic connections between cells. This research program explores how reconsolidation affects the strength of synaptic connections between nerve cells. We seek to understand the mechanisms by which reconsolidation can lead to the modification and erasure of plastic changes in nerve connectivity, and how this process is regulated by previous and ongoing nerve activity. We will use a combination of advanced technical approaches to directly study the chemical connections between nerve cells, and use advanced genetic approaches to selectively activate and study reconsolidation at the synapse in single nerve cells. Additionally, we will identify key proteins that enable reconsolidation to erase memory traces, with the aim of manipulating these proteins to better understand how reconsolidation is activated. Overall these results will greatly enhance our understanding of how the flow of information is regulated in the brain and spinal cord. The study of how reconsolidation is activated at a synapse and how it regulates synaptic strength will yield new insights into how networks of neurons store, access, and update information.