Laboratory of Neuronal Network and Behavior, Institute of Cognitive Neuroscience and Psychology, Research Center for Natural Sciences, Budapest, Hungary.
Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary.
Nat Neurosci. 2020 May;23(5):625-637. doi: 10.1038/s41593-020-0620-z. Epub 2020 Apr 13.
Decades of research support the idea that associations between a conditioned stimulus (CS) and an unconditioned stimulus (US) are encoded in the lateral amygdala (LA) during fear learning. However, direct proof for the sources of CS and US information is lacking. Definitive evidence of the LA as the primary site for cue association is also missing. Here, we show that calretinin (Calr)-expressing neurons of the lateral thalamus (CalrLT neurons) convey the association of fast CS (tone) and US (foot shock) signals upstream from the LA in mice. CalrLT input shapes a short-latency sensory-evoked activation pattern of the amygdala via both feedforward excitation and inhibition. Optogenetic silencing of CalrLT input to the LA prevents auditory fear conditioning. Notably, fear conditioning drives plasticity in CalrLT neurons, which is required for appropriate cue and contextual fear memory retrieval. Collectively, our results demonstrate that CalrLT neurons provide integrated CS-US representations to the LA that support the formation of aversive memories.
几十年来的研究支持这样一种观点，即在恐惧学习过程中，条件刺激 (CS) 和非条件刺激 (US) 之间的关联是在外侧杏仁核 (LA) 中编码的。然而，缺乏 CS 和 US 信息来源的直接证据。LA 作为线索关联的主要部位的明确证据也缺失。在这里，我们表明，外侧丘脑中的钙结合蛋白 (Calr) 表达神经元 (CalrLT 神经元) 在小鼠体内从前侧 LA 传递快速 CS（音调）和 US（足部电击）信号的关联。CalrLT 输入通过前馈兴奋和抑制来塑造杏仁核的短潜伏期感觉诱发激活模式。CalrLT 输入到 LA 的光遗传沉默可防止听觉恐惧条件反射。值得注意的是，恐惧条件反射驱动 CalrLT 神经元的可塑性，这是适当的线索和上下文恐惧记忆检索所必需的。总的来说，我们的结果表明，CalrLT 神经元向 LA 提供整合的 CS-US 表示，支持产生厌恶记忆。
