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Learning-related feedforward inhibitory connectivity growth required for memory precision

机译：学习相关的前馈抑制连接性增长，以提高内存精度

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In the adult brain, new synapses are formed and pre-existing ones are lost, but the function of this structural plasticity has remained unclear. Learning of new skills is correlated with formation of new synapses. These may directly encode new memories, but they may also have more general roles in memory encoding and retrieval processes. Here we investigated how mossy fibre terminal complexes at the entry of hippocampal and cerebellar circuits rearrange upon learning in mice, and what is the functional role of the rearrangements. We show that one-trial and incremental learning lead to robust, circuit-specific, long-lasting and reversible increases in the numbers of filopodial synapses onto fast-spiking interneurons that trigger feedforward inhibition. The increase in feedforward inhibition connectivity involved a majority of the pre-synaptic terminals, restricted the numbers of c-Fos-expressing postsynaptic neurons at memory retrieval, and correlated temporally with the quality of the memory. We then show that for contextual fear conditioning and Morris water maze learning, increased feedforward inhibition connectivity by hippocampal mossy fibres has a critical role for the precision of the memory and the learned behaviour. In the absence of mossy fibre long-term potentiation in Rab3a~(-/-)mice, c-Fos ensemble reorganization and feedforward inhibition growth were both absent in CA3 upon learning, and the memory was imprecise. By contrast, in the absence of adducin 2 (Add2; also known as P-adducin) c-Fos reorganization was normal, but feedforward inhibition growth was abolished. In parallel, c-Fos ensembles in CA3 were greatly enlarged, and the memory was imprecise. Feedforward inhibition growth and memory precision were both rescued by re-expression of Add2 specifically in hippocampal mossy fibres. These results establish a causal relationship between learning-related increases in the numbers of defined synapses and the precision of learning and memory in the adult. The results further relate plasticity and feedforward inhibition growth at hippocampal mossy fibres to the precision of hippocampus-dependent memories.
机译：在成年大脑中，形成了新的突触而失去了先前的突触，但是这种结构可塑性的功能仍不清楚。学习新技能与新突触的形成有关。这些可以直接对新的存储器进行编码，但是它们在存储器编码和检索过程中也可能具有更一般的作用。在这里，我们研究了小鼠学习后如何在海马和小脑回路入口处的苔藓纤维末端复合物重排，以及重排的功能作用是什么。我们表明，一次尝试性学习和渐进学习会导致健壮，特定于电路的，持久的和可逆的fi虫突触到触发快速前馈抑制的中间神经元上的数量增加。前馈抑制连接性的增加涉及大多数突触前末端，限制了在记忆检索时表达c-Fos的突触后突触神经元的数量，并且在时间上与记忆的质量相关。然后我们表明，对于情境恐惧调节和莫里斯水迷宫学习，海马苔藓纤维增加的前馈抑制连通性对记忆和所学行为的精确性具有关键作用。在Rab3a〜（-/-）小鼠中没有长满苔藓纤维的长时程增强时，在学习中CA3中均不存在c-Fos整体重组和前馈抑制生长，并且记忆是不精确的。相比之下，在没有adducin 2（Add2；也称为P-adducin）的情况下，c-Fos重组是正常的，但前馈抑制的生长被取消了。并行地，CA3中的c-Fos集成大大扩大，并且存储不精确。前馈抑制的生长和记忆的精确性都通过在海马长满苔藓的纤维中重新表达Add2得以挽救。这些结果在成年突触的数量与学习有关的增加与成人学习和记忆的精确度之间建立了因果关系。结果进一步将可塑性和前馈抑制生长在海马苔藓纤维上与海马依赖性记忆的精确度相关。

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  • 来源
    《Nature》 |2011年第7348期|p.514-518|共5页
  • 作者

    Sarah Ruediger; Claudia Vittori; Ewa Bednarek; Christel Genoud; Piergiorgio Strata; Benedetto Sacchetti; Pico Caroni;

  • 作者单位

    Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland,Department of Neuroscience and National Institute of Neuroscience-ltaly, C.so Raffaello 30,10125 Torino, Italy;

    Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland;

    Department of Neuroscience and National Institute of Neuroscience-ltaly, C.so Raffaello 30,10125 Torino, Italy;

    Department of Neuroscience and National Institute of Neuroscience-ltaly, C.so Raffaello 30,10125 Torino, Italy;

    Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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