期刊
NATURE
卷 504, 期 7479, 页码 272-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12866
关键词
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资金
- Novartis Research Foundation
- NCCR Synapsy
Learning and memory processes can be influenced by recent experience, but the mechanisms involved are poorly understood. Enhanced plasticity during critical periods of early life is linked to differentiating parvalbumin (PV)-interneuron networks(1-7), suggesting that recent experience may modulate learning by targeting the differentiation state of PV neurons(8-11) in the adult. Here we show that environmental enrichment and Pavlovian contextual fear conditioning induce opposite, sustained and reversible hippocampal PV-network configurations in adult mice. Specifically, enrichment promotes the emergence of large fractions of low-differentiation (low PV and GAD67 expression) basket cells with low excitatory-to-inhibitory synaptic-density ratios, whereas fear conditioning leads to large fractions of high-differentiation (high PV and GAD67 expression) basket cells with high excitatory-to-inhibitory synaptic-density ratios. Pharmacogenetic inhibition or activation of PV neurons was sufficient to induce such opposite low-PV-network or high-PV-network configurations, respectively. The low-PV-network configuration enhanced structural synaptic plasticity(12,13), and memory consolidation and retrieval, whereas these were reduced by the high-PV-network configuration. We then show that maze navigation learning(14) induces a hippocampal low-PV-network configuration paralleled by enhanced memory and structural synaptic plasticity throughout training, followed by a shift to a high-PV-network configuration after learning completion. The shift to a low-PV-network configuration specifically involved increased vasoactive intestinal polypeptide (VIP)-positive GABAergic boutons and synaptic transmission onto PV neurons(15,16). Closely comparable low-and high-PV-network configurations involving VIP boutons were specifically induced in primary motor cortex upon rotarod motor learning(17,18). These results uncover a network plasticity mechanism induced after learning through VIP-PV microcircuit modulation(19), and involving large, sustained and reversible shifts in the configuration of PV basket-cell networks in the adult. This novel form of experience-related plasticity in the adult modulates memory consolidation, retrieval and learning, and might be harnessed for therapeutic strategies to promote cognitive enhancement and neuroprotection.
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