Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science. 2012 Mar 23;335(6075):1513-6. doi: 10.1126/science.1214985.
We investigated the effect of activating a competing, artificially generated, neural representation on encoding of contextual fear memory in mice. We used a c-fos-based transgenic approach to introduce the hM(3)D(q) DREADD receptor (designer receptor exclusively activated by designer drug) into neurons naturally activated by sensory experience. Neural activity could then be specifically and inducibly increased in the hM(3)D(q)-expressing neurons by an exogenous ligand. When an ensemble of neurons for one context (ctxA) was artificially activated during conditioning in a distinct second context (ctxB), mice formed a hybrid memory representation. Reactivation of the artificially stimulated network within the conditioning context was required for retrieval of the memory, and the memory was specific for the spatial pattern of neurons artificially activated during learning. Similar stimulation impaired recall when not part of the initial conditioning.
我们研究了激活竞争的、人为产生的神经表象对小鼠情景恐惧记忆编码的影响。我们使用基于 c-fos 的转基因方法将 hM(3)D(q) DREADD 受体(仅由设计药物激活的设计受体)引入到自然由感觉经验激活的神经元中。然后,可以通过外源性配体特异性和诱导性地增加 hM(3)D(q) 表达神经元的神经活动。当在一个不同的第二个环境(ctxB)中进行条件反射时,一组特定的神经元(ctxA)被人为激活,此时小鼠形成了混合记忆表象。在条件反射环境中重新激活人为刺激的网络是记忆检索所必需的,并且记忆是特定于学习过程中人为激活的神经元的空间模式。类似的刺激如果不是初始条件反射的一部分,则会损害回忆。