Nabavi Sadegh, Fox Rocky, Proulx Christophe D, Lin John Y, Tsien Roger Y, Malinow Roberto
1] Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, University of California at San Diego, California 92093, USA [2].
Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, University of California at San Diego, California 92093, USA.
Nature. 2014 Jul 17;511(7509):348-52. doi: 10.1038/nature13294. Epub 2014 Jun 1.
It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD). However, the causal link between these synaptic processes and memory has been difficult to demonstrate. Here we show that fear conditioning, a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning. Subsequent optogenetic delivery of LTD conditioning to the auditory input inactivates memory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.
有人提出，记忆是通过诸如长时程增强（LTP）和长时程抑制（LTD）等细胞机制对突触强度进行修饰来编码的。然而，这些突触过程与记忆之间的因果联系一直难以证明。在此我们表明，恐惧条件反射，一种联想记忆类型，可分别被LTD和LTP灭活和重新激活。我们首先对动物进行条件训练，使其将足部电击与针对杏仁核（已知对恐惧条件反射至关重要的脑区）的听觉输入的光遗传学刺激联系起来。随后对听觉输入进行LTD条件的光遗传学传递会使电击记忆失活。然后对听觉输入进行LTP条件的后续光遗传学传递会重新激活电击记忆。因此，我们利用LTD和LTP设计了记忆的灭活和重新激活，支持了这些突触过程与记忆之间的因果联系。
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