Chromatin plasticity predetermines neuronal eligibility for memory trace formation
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. Only a small portion of eligible neurons in a certain brain region are available to become part of a memory engram. The mechanism underlying this recruitment of neurons is currently unknown. Santoni et al. addressed this issue by focusing on chromatin plasticity in the lateral amygdala during associative fear learning (see the Perspective by Krabbe). After increasing chromatin plasticity by sparsely overexpressing histone acetyl transferases, neurons with elevated histone acetylation were preferentially enrolled into the engram. This overexpression altered intrinsic excitability of lateral amygdala principal cells, and this was accompanied by increased chromatin accessibility and altered gene expression, mainly of synaptic proteins. These results indicate that a neuron?s epigenetic makeup defines its eligibility to be selected for storing learned information. ?Peter SternMemories 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. Only a small portion of eligible neurons in a certain brain region are available to become part of a memory engram. The mechanism underlying this recruitment of neurons is currently unknown. Santoni et al. addressed this issue by focusing on chromatin plasticity in the lateral amygdala during associative fear learning (see the Perspective by Krabbe). After increasing chromatin plasticity by sparsely overexpressing histone acetyl transferases, neurons with elevated histone acetylation were preferentially enrolled into the engram. This overexpression altered intrinsic excitability of lateral amygdala principal cells, and this was accompanied by increased chromatin accessibility and altered gene expression, mainly of synaptic proteins. These results indicate that a neuron?s epigenetic makeup defines its eligibility to be selected for storing learned information. ?Peter Stern
doi: 10.1126/science.adg9982
