Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095.
Department of Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, California 90095.
J Neurosci. 2020 Oct 21;40(43):8329-8342. doi: 10.1523/JNEUROSCI.1022-20.2020. Epub 2020 Sep 21.
Hippocampal CA1 place cell spatial maps are known to alter their firing properties in response to contextual fear conditioning, a process called "remapping." In the present study, we use chronic calcium imaging to examine remapping during fear retrieval and extinction of an inhibitory avoidance task in mice of both sexes over an extended period of time and with thousands of neurons. We demonstrate that hippocampal ensembles encode space at a finer scale following fear memory acquisition. This effect is strongest near the shock grid. We also characterize the long-term effects of shock on place cell ensemble stability, demonstrating that shock delivery induces several days of high fear and low between-session place field stability, followed by a new, stable spatial representation that appears after fear extinction. Finally, we identify a novel group of CA1 neurons that robustly encode freeze behavior independently from spatial location. Thus, following fear acquisition, hippocampal CA1 place cells sharpen their spatial tuning and dynamically change spatial encoding stability throughout fear learning and extinction. The hippocampus contains place cells that encode an animal's location. This spatial code updates, or remaps, in response to environmental change. It is known that contextual fear can induce such remapping; in the present study, we use chronic calcium imaging to examine inhibitory avoidance-induced remapping over an extended period of time and with thousands of neurons and demonstrate that hippocampal ensembles encode space at a finer scale following electric shock, an effect which is enhanced by threat proximity. We also identify a novel group of freeze behavior-activated neurons. These results suggest that, more than merely shuffling their spatial code following threat exposure, place cells enhance their spatial coding with the possible benefit of improved threat localization.
海马体 CA1 位置细胞的空间图谱已知会根据情境性恐惧条件反射改变其发射特性，这一过程称为“重映射”。在本研究中，我们使用慢性钙成像技术，在雄性和雌性小鼠中，在长时间内并使用数千个神经元，检查恐惧记忆获取后的恐惧检索和消退过程中的重映射。我们证明，海马体集合在恐惧记忆获取后以更精细的尺度对空间进行编码。这种效应在电击网格附近最强。我们还描述了电击对位置细胞集合稳定性的长期影响，证明电击会导致数天的高度恐惧和会话间位置场稳定性降低，随后是在恐惧消退后出现的新的、稳定的空间表示。最后，我们确定了一组新的 CA1 神经元，它们能够独立于空间位置强烈编码冻结行为。因此，在恐惧获得后，海马体 CA1 位置细胞会锐化其空间调谐，并在恐惧学习和消退过程中动态改变空间编码稳定性。海马体包含编码动物位置的位置细胞。这种空间代码会根据环境变化进行更新或重映射。已知情境性恐惧可以诱导这种重映射；在本研究中，我们使用慢性钙成像技术，在长时间内并使用数千个神经元，检查电击诱导的回避诱导的重映射，并证明海马体集合在电击后以更精细的尺度对空间进行编码，这种效应通过威胁接近而增强。我们还确定了一组新的冻结行为激活神经元。这些结果表明，位置细胞在受到威胁后不仅仅是简单地改变其空间代码，而是通过可能改善威胁定位的方式增强其空间编码。
