Progressive Excitability Changes in the Medial Entorhinal Cortex in the 3xTg Mouse Model of Alzheimer's Disease Pathology

被引:0
作者
Chen, Lingxuan [1 ,2 ]
Wick, Zoe Christenson [1 ]
Vetere, Lauren M. [1 ]
Vaughan, Nick [1 ]
Jurkowski, Albert [1 ,3 ]
Galas, Angelina [1 ,4 ]
Diego, Keziah S. [1 ]
Philipsberg, Paul A. [1 ]
Soler, Ivan [1 ]
Feng, Yu [1 ]
Cai, Denise J. [1 ]
Shuman, Tristan [1 ]
机构
[1] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA
[2] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA
[3] CUNY Hunter Coll, New York, NY 10065 USA
[4] NYU, New York, NY 10012 USA
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; electrophysiology; excitability; medial entorhinal cortex; stellate cells; MEMORY DEFICITS; AMYLOID-BETA; A-BETA; NEURONAL EXCITABILITY; LAYER II; INTRINSIC EXCITABILITY; HIPPOCAMPAL-NEURONS; OBJECT LOCATION; CELLS; DYSFUNCTION;
D O I
10.1523/JNEUROSCI.1204-23.2023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in hippocampus, but less is known about changes in medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at 3 and 10 months of age in the 3xTg mouse model of AD pathology, using male and female mice. At 3 months of age, before the onset of memory impairments, we found early hyperexcitability in intrinsic properties of MECII stellate and pyramidal cells, but this was balanced by a relative reduction in synaptic excitation (E) compared with inhibition (I; E/I ratio), suggesting intact homeostatic mechanisms regulating MECII activity. Conversely, MECIII neurons had reduced intrinsic excitability at this early time point with no change in synaptic E/I ratio. By 10 months of age, after the onset of memory deficits, neuronal excitability of MECII pyramidal cells and MECIII excitatory neurons was largely normalized in 3xTg mice. However, MECII stellate cells remained hyperexcitable, and this was further exacerbated by an increased synaptic E/I ratio. This observed combination of increased intrinsic and synaptic hyperexcitability suggests a breakdown in homeostatic mechanisms specifically in MECII stellate cells at this postsymptomatic time point, which may contribute to the emergence of memory deficits in AD.
引用
收藏
页码:7441 / 7454
页数:14
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