Cellular mechanisms underlying short-term memory in the hippocampal CA1 region

点击翻译按钮获取中文摘要

Short-term memory is a cognitive function which enables us to mentally retain information for short periods of time (up to tens of seconds). It is required in daily life in order to understand speech, make decisions, solve problems, and perform many other cognitive functions. Understanding cellular mechanisms and molecular correlates of short-term memory is, therefore, of great importance for maintaining or improving quality of life in neurodegenerative disorders, as well as during natural aging processes in which short-term memory function declines. Classically, it has been believed that sustained spiking activity of neurons (persistent firing) supported by synaptic network maintains information as short-term memory. In contrast, we, and others, have established the involvement of transient receptor potential canonical (TRPC) channels in persistent firing in individual neurons, independent of the synaptic network. However, these studies were limited to in vitro experiments, and for many years it remained unclear whether TRPC channels could support in vivo persistent firing and short term memory performance. More recently, however, the role of TRPC channels in short-term memory and in vivo neural activity has been demonstrated by us, among others, in mice, indicating that TRPC channels may be a key mechanism of short-term memory. In this project, we further clarify the specific role of TRPC channels by resolving the current controversy and by extending our understanding of the role of TRPC channels in vivo in the hippocampus. First, the observation of intact persistent firing in TRPC knock-out mice challenges the role of TRPC channels in persistent firing in individual neurons. We aim to resolve this issue by combining genetic and pharmacological manipulations in vitro. Second, the roles of TRPC channels in neural activity in vivo still remain largely unknown. Therefore, we will conduct in vivo electrophysiological recordings in order to investigate the effect of TRPC channel manipulations on persistent firing and other memory related activity. These experiments will provide insights into the core mechanism of persistent firing and short-term memory, and into cognitive deficits due to aging or pathology.