Pasini Silvia, Corona Carlo, Liu Jin, Greene Lloyd A, Shelanski Michael L
Cell Rep. 2015 Apr 14;11(2):183-91. doi: 10.1016/j.celrep.2015.03.025.
Prior studies suggested that the transcription factor ATF4 negatively regulates synaptic plastic and memory. By contrast, we provide evidence from direct in vitro and in vivo knockdown of ATF4 in rodent hippocampal neurons and from ATF4-null mice that implicate ATF4 as essential for normal synaptic plasticity and memory. In particular, hippocampal ATF4 downregulation produces deficits in long-term spatial memory and behavioral flexibility without affecting associative memory or anxiety-like behavior. ATF4 knockdown or loss also causes profound impairment of both long-term potentiation (LTP) and long-term depression (LTD) as well as decreased glutamatergic function. We conclude that ATF4 is a key regulator of the physiological state necessary for neuronal plasticity and memory.
先前的研究表明，转录因子ATF4对突触可塑性和记忆具有负调控作用。相比之下，我们通过在啮齿动物海马神经元中直接进行体外和体内敲低ATF4以及利用ATF4基因敲除小鼠提供了证据，表明ATF4对正常的突触可塑性和记忆至关重要。特别是，海马ATF4的下调会导致长期空间记忆和行为灵活性的缺陷，而不会影响联想记忆或焦虑样行为。ATF4的敲低或缺失还会导致长时程增强（LTP）和长时程抑制（LTD）的严重受损以及谷氨酸能功能的降低。我们得出结论，ATF4是神经元可塑性和记忆所必需的生理状态的关键调节因子。
