Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences.
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, and.
J Neurosci. 2018 Aug 1;38(31):6854-6863. doi: 10.1523/JNEUROSCI.2976-17.2018. Epub 2018 Jul 9.
The hippocampus is crucial for declarative memories in humans and encodes episodic and spatial memories in animals. Memory coding strengthens synaptic efficacy via an LTP-like mechanism. Given that animals store memories of everyday experiences, the hippocampal circuit must have a mechanism that prevents saturation of overall synaptic weight for the preservation of learning capacity. LTD works to balance plasticity and prevent saturation. In addition, adult neurogenesis in the hippocampus is proposed to be involved in the down-scaling of synaptic efficacy. Here, we show that adult neurogenesis in male rats plays a crucial role in the maintenance of hippocampal capacity for memory (learning and/or memory formation). Neurogenesis regulated the maintenance of LTP, with decreases and increases in neurogenesis prolonging or shortening LTP persistence, respectively. Artificial saturation of hippocampal LTP impaired memory capacity in contextual fear conditioning, which completely recovered after 14 d, which was the time required for LTP to decay to the basal level. Memory capacity gradually recovered in parallel with neurogenesis-mediated gradual decay of LTP. Ablation of neurogenesis by x-ray irradiation delayed the recovery of memory capacity, whereas enhancement of neurogenesis using a running wheel sped up recovery. Therefore, one benefit of ongoing adult neurogenesis is the maintenance of hippocampal memory capacity through homeostatic renewing of hippocampal memory circuits. Decreased neurogenesis in aged animals may be responsible for the decline in cognitive function with age. Learning many events each day increases synaptic efficacy via LTP, which can prevent the storage of new memories in the hippocampal circuit. In this study, we demonstrate that hippocampal capacity for the storage of new memories is maintained by ongoing adult neurogenesis through homoeostatic renewing of hippocampal circuits in rats. A decrease or an increase in neurogenesis, respectively, delayed or sped up the recovery of memory capacity, suggesting that hippocampal adult neurogenesis plays a critical role in reducing LTP saturation and keeps the gate open for new memories by clearing out the old memories from the hippocampal memory circuit.
海马体对于人类的陈述性记忆至关重要,在动物中编码情景和空间记忆。记忆编码通过类似于 LTP 的机制增强突触效能。鉴于动物存储日常经验的记忆,海马体回路必须具有一种机制,防止整体突触权重饱和,以保持学习能力。LTD 起到平衡可塑性和防止饱和的作用。此外,海马体中的成年神经发生被提出与突触效能的缩小有关。在这里,我们表明,雄性大鼠的成年神经发生对于维持海马体的记忆能力(学习和/或记忆形成)至关重要。神经发生调节 LTP 的维持,神经发生的减少和增加分别延长或缩短 LTP 的持续时间。海马体 LTP 的人工饱和会损害情景恐惧条件反射中的记忆能力,这种损害在 14 天后完全恢复,这是 LTP 衰减到基础水平所需的时间。记忆能力逐渐恢复,与神经发生介导的 LTP 逐渐衰减平行。X 射线照射消融神经发生会延迟记忆能力的恢复,而使用跑步轮增强神经发生会加速恢复。因此,持续的成年神经发生的一个好处是通过海马体记忆回路的稳态更新来维持海马体的记忆能力。老年动物中神经发生的减少可能是认知功能随年龄增长而下降的原因。每天学习许多事件会通过 LTP 增强突触效能,从而防止在海马体回路中存储新的记忆。在这项研究中,我们证明了通过大鼠海马体回路的稳态更新,持续的成年神经发生维持了海马体存储新记忆的能力。神经发生的减少或增加分别延迟或加速了记忆能力的恢复,这表明海马体成年神经发生在降低 LTP 饱和方面起着关键作用,并通过从海马体记忆回路中清除旧记忆来保持新记忆的大门打开。