Supplementary Material for: Focal Adhesion Kinase Regulates Neuronal Growth, Synaptic Plasticity and Hippocampus-Dependent Spatial Learning and Memory

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory.

黏着斑激酶（focal adhesion kinase, FAK）是一类在哺乳动物大脑中广泛表达、且在神经元生长锥（neuronal growth cones）中高度富集的非受体酪氨酸激酶（non-receptor tyrosine kinase）。已有研究报道FAK对神经元生长兼具抑制与促进活性，但其在神经元突起生长中的作用仍存在争议。与其他调控神经元生长与可塑性的酪氨酸激酶（如神经营养因子受体）不同，FAK在体内对学习记忆的相关性尚未被明确阐明。因此，本研究采用小鼠模型开展了一项综合性研究，旨在阐明FAK在海马神经元的神经元生长、神经递质释放及突触可塑性中的作用，以及其在海马依赖性学习记忆中的功能。功能获得与功能缺失（gain- and loss-of-function）实验结果表明，FAK是海马细胞形态的关键调控因子。FAK可介导神经营养因子诱导的神经元突起生长，而FAK抑制不仅影响微小兴奋性突触后电位（miniature excitatory postsynaptic potentials），还会干扰活动依赖性海马长时程增强（activity-dependent hippocampal long-term potentiation），这促使我们进一步探索FAK在体内空间学习记忆中的潜在作用。本研究数据显示，FAK具有促进神经元生长的作用，在突触功能调控中发挥重要作用，并可介导体内海马依赖性空间学习记忆过程。