Zaremba Jeffrey D, Diamantopoulou Anastasia, Danielson Nathan B, Grosmark Andres D, Kaifosh Patrick W, Bowler John C, Liao Zhenrui, Sparks Fraser T, Gogos Joseph A, Losonczy Attila
Department of Neuroscience, Columbia University, New York, New York, USA.
Department of Psychiatry, Columbia University, New York, New York, USA.
Nat Neurosci. 2017 Nov;20(11):1612-1623. doi: 10.1038/nn.4634. Epub 2017 Sep 4.
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca imaging in hippocampal area CA1 of wild-type and Df(16)A mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.
海马体位置细胞代表了情景记忆的细胞基础。位置细胞集群会进行重组以支持学习，但也必须维持稳定的表征以促进记忆回忆。尽管进行了广泛的研究，但位置细胞动力学在健康和疾病中与学习相关的作用仍然难以捉摸。我们利用慢性双光子钙成像技术，对野生型小鼠和Df(16)A小鼠（一种22q11.2缺失综合征的动物模型，22q11.2缺失综合征是认知功能障碍和精神分裂症最常见的遗传风险因素之一）海马体CA1区进行研究，发现野生型小鼠的目标导向学习由稳定的空间图谱以及位置野向目标位置的强烈重映射所支持。Df(16)A小鼠表现出明显的学习缺陷，同时伴有空间图谱稳定性降低以及缺乏目标导向的位置细胞重组。这些结果扩展了我们对支持认知灵活性的海马体集群动力学的理解，并证明了它们在22q11.2相关认知功能障碍模型中的重要性。
