Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs-猫眼课题宝

海马神经元的突触后爆发重新激活使时间上不连续的输入具有联想可塑性

DOI：

10.1101/2022.06.23.497305

发表时间：

2022

期刊：

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Fuchsberger T

神经科学中一个基本的悬而未决的问题是，大脑如何与时间上分离的记忆事件相关联。在这里，我们提出重新激活诱导的突触可塑性可以解决这一问题。此前，我们报道了强化信号多巴胺在持续的突触活动中将海马峰时依赖性抑制转化为增强(Brzosko等人，2015)。在这里，我们报告了在多巴胺存在的情况下，突触后爆发在小鼠海马突触中产生输入特异性的长时程增强，在它们被突触前和突触后活动(配对前后；Δt=-20ms)启动10分钟后。这种启动活性诱导突触抑制，并建立NMDA受体依赖的沉默合格痕迹，通过cAMP-PKA级联反应，通过与传统LTP不同的信号通路，迅速转化为蛋白质合成依赖的突触增强。这一突触学习规则被整合到一个计算模型中，我们发现它通过控制记忆分配并使“指导性”和“监督”强化学习成为可能，从而增加了强化学习的特异性。我们预测，这种机制将使重新激活的神经元比未重新激活的细胞激活得更强烈，并携带更多的空间信息，这在执行基于奖励的导航任务的自由活动小鼠中得到了证实。

A fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here, we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produce input-specific LTP in mouse hippocampal synapses 10 min after they were primed with coincident pre-and post-synaptic activity (post-before-pre pairing; Δt=–20 ms). This priming activity induces synaptic depression and sets an NMDA receptor-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. This synaptic learning rule was incorporated into a computational model, and we found that it adds specificity to reinforcement learning by controlling memory allocation and enabling both ‘instructive’and ‘supervised’reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.