Neonatal infection modulates behavioral flexibility and hippocampal activation on a Morris Water Maze task.

Neonatal infection modulates behavioral flexibility and hippocampal activation on a Morris Water Maze task.
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DOI:
10.1016/j.physbeh.2014.02.033
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发表时间:
2014-04-22
影响因子:
2.9
通讯作者:
Bilbo SD
Bilbo SD
中科院分区:
医学3区
文献类型:
--
作者:
Williamson LL;Bilbo SD

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新生儿感染在细胞和行为水平上对大脑都有持久的影响。我们确定了大鼠出生后第4天(P)周感染大肠杆菌对成年后水迷宫任务的影响,并在记忆测试后评估了齿状回(DG)的神经元激活。大鼠在3种不同的水迷宫任务范式中进行训练和测试:1)最小训练(18次/ 3天),2)扩展训练(50次/ 10天)或3)逆转训练(扩展训练后在新的平台位置进行30次/ 3天)。在48小时记忆测试后,采集大脑,使用DG中活动调节的细胞骨架相关(Arc)蛋白评估神经元激活情况。经过最低限度的训练后,与早期接受PBS治疗的对照大鼠相比,接受大肠杆菌治疗的新生大鼠在记忆测试中表现更好,反而减少了Arc表达。然而,在长时间训练后的记忆测试中,新生感染的大鼠在行为或神经元激活方面与对照大鼠没有区别。此外,与对照组不同,用大肠杆菌治疗过的新生大鼠在48小时的逆转平台位置记忆测试中明显受损。具体来说,虽然新生感染的大鼠能够以与对照组相同的速度获得新位置,但在记忆测试中,它们在逆转平台的目标象限中花费的时间明显减少。然而,在48HR记忆逆转测试后,新生儿感染大鼠和对照大鼠的Arc表达水平相似。总之,这些数据表明,新生儿感染可能提高海马体依赖性任务的习得率,同时损害相同任务的灵活性;此外,学习过程中DG的网络激活可能预示着海马依赖任务的未来认知灵活性。
Neonatal infection has enduring effects on the brain, both at the cellular and behavioral levels. We determined the effects of peripheral infection with Escherichia coli at postnatal day (P) 4 in rats on a water maze task in adulthood, and assessed neuronal activation in the dentate gyrus (DG) following the memory test. Rats were trained and tested on one of 3 distinct water maze task paradigms: 1) minimal training (18 trials/ 3 days), 2) extended training (50 trials/ 10 days) or 3) reversal training (extended training followed by 30 trials/ 3 days with a new platform location). Following a 48HR memory test, brains were harvested to assess neuronal activation using activity-regulated cytoskeleton-associated (Arc) protein in the DG. Following minimal training, rats treated neonatally with E. coli had improved performance and paradoxically reduced Arc expression during the memory test compared to control rats treated with PBS early in life. However, neonatally-infected rats did not differ from control rats in behavior or neuronal activation during the memory test following extended training. Furthermore, rats treated neonatally with E. coli were significantly impaired during the 48HR memory test for a reversal platform location, unlike controls. Specifically, whereas neonatally-infected rats were able to acquire the new location at the same rate as controls, they spent significantly less time in the target quadrant for the reversal platform during a memory test. However, neonatally-infected and control rats had similar levels of Arc expression following the 48HR memory test for reversal. Together, these data indicate that neonatal infection may improve the rate of acquisition on hippocampal-dependent tasks while impairing flexibility on the same tasks; in addition, network activation in the DG during learning may be predictive of future cognitive flexibility on a hippocampal-dependent task.
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