Datta Subimal, Saha Subhash, Prutzman Sarah L, Mullins Olivia J, Mavanji Vijayakumar
Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry and Program in Behavioral Neuroscience, Boston University School of Medicine, Boston, MA 02118, USA.
J Neurosci Res. 2005 Jun 1;80(5):727-37. doi: 10.1002/jnr.20501.
The aim of this study was to test the hypothesis that the dorsal hippocampus plays a critical role in pontine-wave (P-wave) generator activation-dependent memory processing of two-way active avoidance (TWAA) learning. To achieve this objective, rats were given small bilateral lesions in the CA1, dentate gyrus (DG), or CA3 region of the dorsal hippocampus by microinjecting ibotenic acid. After recovery, lesioned and sham-lesioned rats were trained on a TWAA learning paradigm, allowed a 6-hr period of undisturbed sleep, and then were tested on the same TWAA paradigm. It was found that lesions in the CA3 region impaired retention of avoidance learning. Conversely, lesions in the CA1 and DG regions had no effect on TWAA learning retention. None of the groups showed any changes in the baseline sleep-wake cycle or in the acquisition of TWAA learning. All rats showed increased rapid eye movement (REM) sleep and increased REM sleep P-wave density during the subsequent 6-hr recording period. Impaired retention in the CA3 group occurred despite an increase in REM sleep and P-wave density, suggesting that during REM sleep, the P-wave generator interacts with the CA3 region of the dorsal hippocampus to aid in consolidation of TWAA learning. The results of the present study thus demonstrate that P-wave generator activation-dependent consolidation of memory requires an intact CA3 subfield of the dorsal hippocampus. The results also provide evidence that under mnemonic pressure, the dorsal hippocampus may not be involved directly in regulating the sleep-wake cycle.
背侧海马体在双向主动回避(TWAA)学习的脑桥波(P波)发生器激活依赖性记忆处理中起关键作用。为实现这一目标,通过微量注射鹅膏蕈氨酸,在大鼠背侧海马体的CA1、齿状回(DG)或CA3区域造成双侧小损伤。恢复后,对损伤组和假损伤组大鼠进行TWAA学习范式训练,给予6小时不受干扰的睡眠,然后在相同的TWAA范式上进行测试。结果发现,CA3区域的损伤损害了回避学习的记忆保持。相反,CA1和DG区域的损伤对TWAA学习记忆保持没有影响。所有组在基线睡眠-觉醒周期或TWAA学习的获得方面均未显示任何变化。在随后6小时的记录期内,所有大鼠的快速眼动(REM)睡眠均增加,REM睡眠P波密度也增加。尽管REM睡眠和P波密度增加,但CA3组的记忆保持仍受损,这表明在REM睡眠期间,P波发生器与背侧海马体的CA3区域相互作用,以帮助巩固TWAA学习。因此,本研究结果表明,P波发生器激活依赖性记忆巩固需要背侧海马体完整的CA3亚区。结果还提供了证据,表明在记忆压力下,背侧海马体可能不直接参与调节睡眠-觉醒周期。