IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning

Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hui; Wang, Yanying; Li, Dapeng; Südhof, Thomas C.; Cao, Peng

doi:10.1016/j.neuron.2017.06.015

Cited by 54 publications

(43 citation statements)

References 79 publications

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“…Novel-object recognition: Novel-object recognition assay was carried out as described previously [16][17][18] . Two identical cubes were placed at the right and left corners of the apparatus.…”

Section: Memory-related Testsmentioning

confidence: 99%

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Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice

Liu

Mao

et al. 2020

Cell Death Dis

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Autism spectrum disorder (ASD) is a neurodevelopmental disease with a strong heritability, but recent evidence suggests that epigenetic dysregulation may also contribute to the pathogenesis of ASD. Especially, increased methylation at the MECP2 promoter and decreased MECP2 expression were observed in the brains of ASD patients. However, the causative relationship of MECP2 promoter methylation and ASD has not been established. In this study, we achieved locus-specific methylation at the transcription start site (TSS) of Mecp2 in Neuro-2a cells and in mice, using nuclease-deactivated Cas9 (dCas9) fused with DNA methyltransferase catalytic domains, together with five locus-targeting sgRNAs. This locus-specific epigenetic modification led to a reduced Mecp2 expression and a series of behavioral alterations in mice, including reduced social interaction, increased grooming, enhanced anxiety/depression, and poor performance in memory tasks. We further found that specifically increasing the Mecp2 promoter methylation in the hippocampus was sufficient to induce most of the behavioral changes. Our finding therefore demonstrated for the first time the casual relationship between locus-specific DNA methylation and diseases symptoms in vivo, warranting potential therapeutic application of epigenetic editing.

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Section: Memory-related Testsmentioning

confidence: 99%

“…Social transmission of food preference (STFP): STFP assay was performed as described previously 17,18 . In this test, each mouse (observer) was fasted for 16 h in a single cage before test.…”

Section: Memory-related Testsmentioning

confidence: 99%

Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice

Liu

Mao

et al. 2020

Cell Death Dis

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“…shown to modulate GABAergic transmission in the olfactory bulb (13). However, an IGF-I mediated long lasting depression of fast GABAergic synaptic transmission in the neocortex has not been described before.…”

Section: Discussionmentioning

confidence: 92%

“…Purkinje cells in the cerebellum (10), or a long-term potentiation of GABA release in the olfactory bulb (13). However, whether IGF-I modulates inhibitory synaptic transmission in the neocortex remains unexplored.…”

Section: Igf-i Also Produces a Long-lasting Depression Of Glutamate-mmentioning

confidence: 99%

IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

Noriega-Prieto

Maglio

Zegarra-Valdivia

et al. 2020

Preprint

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Insulin-like growth factor-I (IGF-I) signaling plays key regulatory roles in multiple processes of brain physiology and pathology. While the direct effects of IGF-I in neurons have been extensively studied, the astrocyte involvement in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. Here we show that IGF-I induces the long-term depression (LTD) of inhibitory synaptic transmission in the mouse barrel cortex. This LTD requires the activation of the IGF-I receptor (IGF-IR) in astrocytes, which stimulates astrocyte Ca 2+ signaling and the release of ATP/adenosine that in turn activates A 2A adenosine receptors at presynaptic inhibitory terminals. Specific deletion of IGF-IR in cortical astrocytes (IGF-IR -/-) impaired the behavioral performance in a whisker discrimination task. These results show novel mechanisms and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing astrocytes as key elements in these processes.

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“…The temporal span or distance between choice odours was varied to further determine whether enrichment affected the ability to temporally resolve past events. As mice are heavily reliant on olfaction for food seeking, social interactions, as well as predator avoidance (Perry et al, 2016 ; Liu et al, 2017 ), assessment of this sensory modality provides an ideal means to explore naturalistic behaviour.…”

Section: Introductionmentioning

confidence: 99%

Environmental Enrichment Expedites Acquisition and Improves Flexibility on a Temporal Sequencing Task in Mice

Rountree-Harrison

Burton

Leamey

et al. 2018

Front. Behav. Neurosci.

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Environmental enrichment (EE) via increased opportunities for voluntary exercise, sensory stimulation and social interaction, can enhance the function of and behaviours regulated by cognitive circuits. Little is known, however, as to how this intervention affects performance on complex tasks that engage multiple, definable learning and memory systems. Accordingly, we utilised the Olfactory Temporal Order Discrimination (OTOD) task which requires animals to recall and report sequence information about a series of recently encountered olfactory stimuli. This approach allowed us to compare animals raised in either enriched or standard laboratory housing conditions on a number of measures, including the acquisition of a complex discrimination task, temporal sequence recall accuracy (i.e., the ability to accurately recall a sequences of events) and acuity (i.e., the ability to resolve past events that occurred in close temporal proximity), as well as cognitive flexibility tested in the style of a rule reversal and an Intra-Dimensional Shift (IDS). We found that enrichment accelerated the acquisition of the temporal order discrimination task, although neither accuracy nor acuity was affected at asymptotic performance levels. Further, while a subtle enhancement of overall performance was detected for both rule reversal and IDS versions of the task, accelerated performance recovery could only be attributed to the shift-like contingency change. These findings suggest that EE can affect specific elements of complex, multi-faceted cognitive processes.

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IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning

Cited by 54 publications

References 79 publications

Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice

Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice

IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation

Environmental Enrichment Expedites Acquisition and Improves Flexibility on a Temporal Sequencing Task in Mice

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