Good Mark A, Bannerman David M
School of Psychology, Cardiff University, Park Place, Cardiff, UK.
Department of Experimental Psychology, University of Oxford, Oxford, UK.
Curr Top Behav Neurosci. 2025;69:27-48. doi: 10.1007/7854_2024_565.
A decline in hippocampal function has long been associated with the progression of cognitive impairments in patients with Alzheimer's disease (AD). The disruption of hippocampal synaptic plasticity [primarily the reduction of long-term potentiation LTP] by excess production of soluble beta-amyloid (Aβ) has long been accepted as the mechanism by which AD pathology impairs memory, at least during the early stages of AD pathogenesis. However, the premise that hippocampal LTP underpins the formation of associative, long-term memories has been challenged. Here, we consider evidence that this canonical view of LTP needs to be refined. Similarly, the view that the hippocampus simply supports memory ignores the wealth of data showing that the hippocampus is functionally heterogeneous along its septo-temporal axis. The ventral (but not the dorsal) hippocampus plays a major role in modulating emotional reactions to conflict. Here, we suggest that hippocampal LTP is not involved in forming long-term associative memories, but instead contributes to the disambiguation of overlapping memories in situations of conflict and associative interference. This conceptualisation of hippocampal synaptic plasticity may help explain how early-stage AD pathology may impact both memory and anxiety.
长期以来，海马体功能衰退一直与阿尔茨海默病（AD）患者认知障碍的进展相关。可溶性β淀粉样蛋白（Aβ）过量产生导致海马体突触可塑性破坏（主要是长期增强作用LTP降低），长期以来一直被认为是AD病理损害记忆的机制，至少在AD发病机制的早期阶段是如此。然而，海马体LTP是联想性长期记忆形成基础的这一前提受到了挑战。在此，我们考虑一些证据，表明对LTP的这一传统观点需要加以完善。同样，认为海马体仅仅支持记忆的观点忽视了大量数据，这些数据表明海马体沿其隔颞轴在功能上是异质的。腹侧（而非背侧）海马体在调节对冲突的情绪反应中起主要作用。在此，我们提出海马体LTP不参与形成长期联想记忆，而是在冲突和联想干扰情况下有助于区分重叠记忆。这种对海马体突触可塑性的概念化可能有助于解释早期AD病理如何影响记忆和焦虑。
