Tian Chengju, Reyes Isabel, Johnson Alexandra, Masurkar Arjun V
Center for Cognitive Neurology, Department of Neurology, NYU Grossman School of Medicine, New York, New York, USA.
Department of Neuroscience & Physiology, NYU Grossman School of Medicine, New York, New York, USA.
Hippocampus. 2025 Sep;35(5):e70025. doi: 10.1002/hipo.70025.
Synaptic spine loss is an early pathophysiologic hallmark of Alzheimer disease (AD) that precedes overt loss of dendritic architecture and frank neurodegeneration. While spine loss signifies a decreased engagement of postsynaptic neurons by presynaptic targets, the degree to which loss of spines and their passive components impacts the excitability of postsynaptic neurons and responses to surviving synaptic inputs is unclear. Using passive multicompartmental models of CA1 pyramidal neurons (PNs), implicated in early AD, we find that spine loss alone drives a boosting of remaining inputs to their proximal and distal dendrites, targeted by CA3 and entorhinal cortex (EC), respectively. This boosting effect is higher in distal versus proximal dendrites and can be mediated by spine loss restricted to the distal compartment, enough to impact synaptic input integration, somatodendritic backpropagation, and plateau potential generation. This has particular relevance to very early stages of AD in which pathophysiology extends from EC to CA1.
突触棘丧失是阿尔茨海默病（AD）早期的病理生理学标志，它先于明显的树突结构丧失和明显的神经退行性变。虽然棘丧失意味着突触后神经元与突触前靶点的接触减少，但棘及其被动成分的丧失对突触后神经元兴奋性和对存活突触输入反应的影响程度尚不清楚。利用与早期AD相关的CA1锥体神经元（PNs）的被动多室模型，我们发现仅棘丧失就会促使分别由CA3和内嗅皮质（EC）靶向的近端和远端树突的剩余输入增强。这种增强效应在远端树突中比近端树突中更高，并且可以由仅限于远端区室的棘丧失介导，足以影响突触输入整合、体树突逆向传播和平原电位产生。这与AD的极早期阶段特别相关，在该阶段病理生理学从EC扩展到CA1。
