Enhanced ventral hippocampal synaptic transmission and impaired synaptic plasticity in a rodent model of alcohol addiction vulnerability
Enhanced ventral hippocampal synaptic transmission and impaired synaptic plasticity in a rodent model of alcohol addiction vulnerability
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DOI：
10.1038/s41598-017-12531-z
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发表时间：
2017-09-26
影响因子：
4.6
通讯作者：
Weiner, Jeffrey L.
中科院分区：
文献类型：
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作者：
Almonte, Antoine G.;Ewin, Sarah E.;Weiner, Jeffrey L.
长期以来，人们认识到，青春期是一个独特的脆弱时期，长期暴露于压力源可能会促使成年后出现广泛的精神障碍和成瘾。然而，神经生物学的基板和完整的剧目的适应这些基板使青春期一个特别敏感的发展阶段还没有得到很好的理解。先前的工作已经表明，青少年社会隔离（aSI）的啮齿动物模型产生了强大的和持久的增加，在表型相关的焦虑/应激障碍和酒精成瘾，包括焦虑，恐惧消退的赤字，增加乙醇消费。在这里，我们使用海马切片的胞外场记录来研究aSI引起的突触功能和突触可塑性的适应性。我们证明，这种早期生活的压力导致增强兴奋性突触传递和海马Schaffer侧支-CA 1突触的长时程增强水平降低。此外，这些变化主要局限于腹侧海马。由于腹侧海马体是调节情绪行为的神经回路的组成部分，我们的研究结果增加了越来越多的证据，表明aSI对调节情感状态的大脑区域有深远的影响。这些研究也为我们最近提出的aSI模型作为酒精成瘾脆弱性的有效模型提供了额外的支持。
It has long been appreciated that adolescence represents a uniquely vulnerable period when chronic exposure to stressors can precipitate the onset of a broad spectrum of psychiatric disorders and addiction in adulthood. However, the neurobiological substrates and the full repertoire of adaptations within these substrates making adolescence a particularly susceptible developmental stage are not well understood. Prior work has demonstrated that a rodent model of adolescent social isolation (aSI) produces robust and persistent increases in phenotypes relevant to anxiety/stressor disorders and alcohol addiction, including anxiogenesis, deficits in fear extinction, and increased ethanol consumption. Here, we used extracellular field recordings in hippocampal slices to investigate adaptations in synaptic function and synaptic plasticity arising from aSI. We demonstrate that this early life stressor leads to enhanced excitatory synaptic transmission and decreased levels of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses. Further, these changes were largely confined to the ventral hippocampus. As the ventral hippocampus is integral to neurocircuitry that mediates emotional behaviors, our results add to mounting evidence that aSI has profound effects on brain areas that regulate affective states. These studies also lend additional support to our recent proposal of the aSI model as a valid model of alcohol addiction vulnerability.