Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs.
Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs.
复制标题
海马神经元的突触后爆发再激活使时间不连续输入的联想可塑性。
DOI：
10.7554/elife.81071
复制
发表时间：
2022-10-13
期刊：
影响因子：
7.7
通讯作者：
Paulsen O
中科院分区：
文献类型：
--
作者：
Fuchsberger T;Clopath C;Jarzebowski P;Brzosko Z;Wang H;Paulsen O
神经科学中一个尚未解决的基本问题是，大脑如何在记忆中关联在时间上分离的事件。在这里，我们提出，再激活诱导的突触可塑性可以解决这个问题。先前，我们报道了在持续的突触活动期间，强化信号多巴胺将海马尖峰时间依赖性抑制转化为增强（Brzosko等人，2015年）。在这里，我们报告了在小鼠海马突触中，多巴胺存在下的突触后爆发在突触前和突触后活动同时启动后10分钟（后-前-前配对; Δt = -20 ms）产生输入特异性LTP。这种引发活性诱导突触抑制，并设置NMDA受体依赖性沉默的资格痕迹，通过cAMP-PKA级联反应，迅速转化为蛋白质合成依赖性突触增强，介导的信号通路不同于传统的LTP。这种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和实现“指导性”和“监督性”强化学习来增加强化学习的特异性。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更强烈地激活并携带更多的空间信息，这在执行奖励导航任务的自由移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.