Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Biological Optical Microscopy Platform, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Neurobiol Learn Mem. 2020 Feb;168:107139. doi: 10.1016/j.nlm.2019.107139. Epub 2019 Dec 13.
Memory is thought to be encoded within networks of neurons within the brain, but the identity of the neurons involved and circuits they form have not been described for any memory. Previously, we used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in different regions of the brain which were specifically activated following fear conditioning. This suggested that these populations of neurons form nodes in a network that encodes fear memory. In particular, one population of learning activated neurons was found within a discrete region of the lateral amygdala (LA), a key nucleus required for fear conditioning. In order to provide evidence that this population is directly involved in fear conditioning, we have analysed the expression of a key molecular requirement for fear conditioning in LA, phosphorylated Extracellular Signal Regulated Kinase 1 and 2 (pERK1/2). The only neurons in LA that specifically expressed pERK1/2 following auditory fear conditioning were in the ventrolateral nucleus of the LA (LAvl), in the same discrete region where we found learning specific FTL neurons. Double labelling experiments in FTL mice showed that a substantial proportion of the learning activated neurons expressed both pERK1/2 and FTL. These experiments provide clear evidence that the learning specific neurons we identified within LAvl are directly involved in auditory fear conditioning. In addition, learning specific expression of pERK1/2 was found in a dense network of dendrites contained within the border region of the LAvl. This network of dendrites may represent an activated dendritic field involved in fear conditioning in LA.
记忆被认为是在大脑中的神经元网络中编码的，但涉及的神经元的身份和它们形成的回路尚未被描述为任何记忆。以前，我们使用 fos-tau-lacZ（FTL）转基因小鼠来识别大脑不同区域中特定激活的离散神经元群体，这些神经元群体在恐惧条件作用后被特异性激活。这表明这些神经元群体形成了编码恐惧记忆的网络节点。特别是，在外侧杏仁核（LA）的一个离散区域内发现了一群学习激活的神经元，这是恐惧条件作用所必需的关键核团。为了提供证据表明这群神经元直接参与恐惧条件作用，我们分析了 LA 中恐惧条件作用的关键分子要求（磷酸化细胞外信号调节激酶 1 和 2（pERK1/2）的表达。在 LA 中，只有在听觉恐惧条件作用后才特异性表达 pERK1/2 的神经元位于 LA 的腹外侧核（LAvl），在我们发现学习特异性 FTL 神经元的同一离散区域中。在 FTL 小鼠中的双标记实验表明，相当一部分学习激活的神经元同时表达 pERK1/2 和 FTL。这些实验提供了明确的证据，表明我们在 LAvl 中鉴定的学习特异性神经元直接参与了听觉恐惧条件作用。此外，在 LAvl 的边界区域内发现了学习特异性表达的 pERK1/2 存在于密集的树突网络中。这个树突网络可能代表了 LA 中恐惧条件作用涉及的激活树突场。
