Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.

学习与突触和电路特性的改变有关，但哺乳动物中存储信息的精确变化在很大程度上仍不清楚。我们将基因靶向电压成像与突触前和后神经元的靶向光遗传学激活和沉默相结​​合，研究海马行为时间尺度可塑性的机制。在虚拟现实环境中导航的小鼠中，特定位置处单个 CA1 细胞的定向光遗传学激活诱导了目标细胞中这些位置的稳定表征。行为小鼠中突触传递的光学引发、记录和调节表明，突触前 CA2/3 细胞的活性是诱导 CA1 可塑性所必需的，此外，在单个 CA1 细胞中诱导这些位置场的过程中，来自突触前 CA2/3 细胞的突触输入CA2/3 在这些相同细胞上的作用被增强。这些结果揭示了海马行为时间尺度可塑性的突触实现，并定义了一种解决行为哺乳动物学习和记忆过程中突触可塑性的方法。