Synaptic basis of feature selectivity in hippocampal neurons

A central question in neuroscience is how synaptic plasticity shapes the
feature selectivity of neurons in behaving animals. Hippocampal CA1
pyramidal neurons display one of the most striking forms of feature
selectivity by forming spatially and contextually selective receptive
fields called place fields, which serve as a model for studying the
synaptic basis of learning and memory. Various forms of synaptic
plasticity have been proposed as cellular substrates for the emergence of
place fields. However, despite decades of work, our understanding of how
synaptic plasticity underlies place field formation and memory encoding
remains limited, largely due to a shortage of tools and technical
challenges associated with the visualization of synaptic plasticity at
single-neuron resolution in awake-behaving animals. To address this, we
developed an all-optical approach to monitor the spatiotemporal tuning and
synaptic weight changes of dendritic spines, before and after the
induction of a place field in single CA1 pyramidal neurons during spatial
navigation. We identified a temporally asymmetric synaptic plasticity
kernel resulting from bidirectional modifications of synaptic weights
around the induction of a place field. Surprisingly, our work uncovered
compartment-specific differences in the magnitude and temporal expression
of synaptic plasticity between basal and oblique dendrites. Our results
provide the first experimental evidence linking synaptic plasticity to the
rapid emergence of spatial selectivity in hippocampal neurons, a critical
prerequisite for episodic memory.

神经科学的核心问题之一是突触可塑性如何塑造行为动物中神经元的特征选择性。海马CA1区锥体神经元通过形成空间和情境选择性的感受野（称为位置野，place fields），展现出最显著的特征选择性形式之一，这些位置野是研究学习和记忆突触基础的模型。多种形式的突触可塑性被认为是位置野形成的细胞底物。然而，尽管经过数十年研究，我们对突触可塑性如何支撑位置野形成和记忆编码的理解仍然有限，这主要是由于缺乏工具以及在清醒行为动物中以单神经元分辨率可视化突触可塑性相关的技术挑战。为解决这一问题，我们开发了一种全光学方法，用于监测空间导航期间单CA1锥体神经元中位置野诱导前后树突棘的时空调谐和突触权重变化。我们发现了一种时间不对称的突触可塑性核心，其源于位置野诱导前后突触权重的双向修饰。令人惊讶的是，我们的研究揭示了基底树突和斜树突之间突触可塑性的强度和时间表达存在区室特异性差异（compartment-specific differences）。我们的结果提供了首个实验证据，将突触可塑性与海马神经元空间选择性的快速形成联系起来，这是情景记忆的关键前提。