Isolation rearing-induced deficits in contextual fear learning do not require CRF(2) receptors.
Isolation rearing-induced deficits in contextual fear learning do not require CRF(2) receptors.
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DOI：
10.1016/j.bbr.2010.01.018
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Powell, Susan B.
中科院分区：
文献类型：
--
作者：
Gresack, Jodi E.;Risbrough, Victoria B.;Scott, Christine N.;Coste, Sarah;Stenzel-Poore, Mary;Geyer, Mark A.;Powell, Susan B.
关键词：
啮齿动物断奶后的社会隔离被用来模拟与神经精神疾病（包括精神分裂症以及焦虑和情绪障碍）相关的发育应激源。隔离饲养引起情绪记忆和海马神经病理学的改变。促肾上腺皮质激素释放因子（CRF）信号通路最近被证明参与了隔离饲养的行为效应。CRF2受体的激活与压力诱导的恐惧学习改变有关，也可能参与长期适应压力。在这里，我们测试的假设，CRF2有助于情绪记忆的孤立养育效果。在断奶时，将小鼠以3只为一组或单独饲养在标准小鼠笼中。在成年期，隔离饲养的小鼠表现出显着减少特定的上下文，但不是特定的线索，冻结。隔离饲养的小鼠在短暂暴露于一个新的环境中的运动探索没有表现出显着的变化，这表明减少冻结响应上下文线索是不是由于活动混淆。隔离饲养也破坏了CRF2基因无效突变小鼠的背景恐惧记忆，这表明CRF2受体对恐惧记忆的隔离效果并不需要。因此，隔离饲养破坏了依赖于大脑的恐惧学习，如在两个单独的小鼠队列中上下文条件冻结的一致减少所示，并且这些影响是通过CRF2独立的机制。这些发现可能与临床相关，因为它们表明，小鼠的隔离饲养可能是一种有用的模型，与各种神经精神疾病中的情感记忆中断有关。
Post-weaning social isolation of rodents is used to model developmental stressors linked to neuropsychiatric disorders including schizophrenia as well as anxiety and mood disorders. Isolation rearing produces alterations in emotional memory and hippocampal neuropathology. Corticotropin releasing factor (CRF) signaling has recently been shown to be involved in behavioral effects of isolation rearing. Activation of the CRF2 receptor is linked to stress-induced alterations in fear learning and may also be involved in long term adaptation to stress. Here we tested the hypothesis that CRF2 contributes to isolation rearing effects on emotional memory. At weaning, mice were housed either in groups of 3 or individually in standard mouse cages. In adulthood, isolation-reared mice exhibited significant reductions in context-specific, but not cue-specific, freezing. Isolation reared mice exhibited no significant changes in locomotor exploration during brief exposure to a novel environment, suggesting that the reduced freezing in response to context cues was not due to activity confounds. Isolation rearing also disrupted context fear memory in mice with a CRF2 gene null mutation, indicating that the CRF2 receptor is not required for isolation effects on fear memory. Thus, isolation rearing disrupts hippocampal-dependent fear learning as indicated by consistent reductions in context-conditioned freezing in two separate cohorts of mice, and these effects are via a CRF2-independent mechanism. These findings may be clinically relevant because they suggest that isolation rearing in mice may be a useful model of developmental perturbations linked to disruptions in emotional memory in a variety of neuropsychiatric disorders.
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