Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys

Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys
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DOI:
10.1093/cercor/bhh144
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发表时间:
2005-04-01
期刊:
影响因子:
3.7
通讯作者:
Luebke, JI
Luebke, JI
中科院分区:
医学2区
文献类型:
--
作者:
Chang, YM;Rosene, DL;Luebke, JI

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由前额皮质(PFC)介导的与年龄相关的高级认知能力显着缺陷的神经生物学基础尚不清楚。为了解决这个问题,使用全细胞电流钳记录来比较年轻和老年恒河猴 PFC 切片中 2/3 层锥体细胞的内在膜和动作电位 (AP) 放电特性。大多数老年受试者在延迟不匹配样本 (DNMS) 任务采集、DNMS 2 分钟延迟和延迟识别跨度任务中表现出较差的表现。相对于年轻细胞,老化细胞的静息膜电位和膜时间常数没有差异,但老化细胞的输入电阻明显更大。单个 AP 在阈值、持续时间或上升时间方面没有差异,但其幅度和下降时间在老化细胞中显着降低。老化细胞中重复的 AP 放电率显着增加。在老年组中,放电率和每项行为任务的表现之间存在 U 形二次关系。表现出低或非常高放电率的受试者表现出较差的表现,而表现出中等放电率的受试者则表现出相对较好的表现。这些数据表明,AP 放电率的增加可能是与年龄相关的 PFC 功能障碍的部分原因。
The neurobiological substrates of significant age-related deficits in higher cognitive abilities mediated by the prefrontal cortex (PFC) are unknown. To address this issue, whole-cell current-clamp recordings were used to compare the intrinsic membrane and action potential (AP) firing properties of layer 2/3 pyramidal cells in PFC slices from young and aged behaviorally characterized rhesus monkeys. Most aged subjects demonstrated impaired performance in Delayed Non-Match to Sample (DNMS) task acquisition, DNMS 2 min delay and the Delayed Recognition Span task. Resting membrane potential and membrane time constant did not differ in aged relative to young cells, but input resistance was significantly greater in aged cells. Single APs did not differ in terms of threshold, duration or rise time, but their amplitude and fall time were significantly decreased in aged cells. Repetitive AP firing rates were significantly increased in aged cells. Within the aged group, there was a U-shaped quadratic relationship between firing rate and performance on each behavioral task. Subjects who displayed either low or very high firing rates exhibited poor performance, while those who displayed intermediate firing rates exhibited relatively good performance. These data indicate that an increase in AP firing rate may be responsible, in part, for age-related PFC dysfunction.