Laboratory of Neuroepigenetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Laboratory of Behavioural Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Science. 2024 Jul 26;385(6707):eadg9982. doi: 10.1126/science.adg9982.
Memories are encoded by sparse populations of neurons but how such sparsity arises remains largely unknown. We found that a neuron's eligibility to be recruited into the memory trace depends on its epigenetic state prior to encoding. Principal neurons in the mouse lateral amygdala display intrinsic chromatin plasticity, which when experimentally elevated favors neuronal allocation into the encoding ensemble. Such chromatin plasticity occurred at genomic regions underlying synaptic plasticity and was accompanied by increased neuronal excitability in single neurons in real time. Lastly, optogenetic silencing of the epigenetically altered neurons prevented memory expression, revealing a cell-autonomous relationship between chromatin plasticity and memory trace formation. These results identify the epigenetic state of a neuron as a key factor enabling information encoding.
记忆是由稀疏的神经元群体编码的，但这种稀疏性是如何产生的，在很大程度上仍然未知。我们发现，神经元被招募到记忆痕迹中的资格取决于其在编码前的表观遗传状态。小鼠外侧杏仁核中的主要神经元表现出内在的染色质可塑性，实验中升高这种可塑性有利于神经元分配到编码集合中。这种染色质可塑性发生在突触可塑性的基因组区域，同时伴随着单个神经元实时兴奋性的增加。最后，光遗传学沉默表观遗传改变的神经元阻止了记忆表达，揭示了染色质可塑性和记忆痕迹形成之间的细胞自主性关系。这些结果表明，神经元的表观遗传状态是实现信息编码的关键因素。
