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Fear Conditioning Leads to Enduring Alterations in RNA Transcripts in Hippocampal Neuropil that are Dependent on EphB2 Forward Signaling

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Abstract

Alterations in mRNA transcription have been associated with changes in brain functions. We wanted to examine if fear conditioning causes long-term changes in transcriptome profiles in the basolateral amygdala (BLA) and hippocampus using RNA-Seq and laser microdissection microscopy. We further aimed to uncover whether these changes are involved in memory formation by monitoring their levels in EphB2lacZ/lacZ mice, which lack EphB2 forward signaling and can form short-term fear conditioning memory but not long-term fear conditioning memory. We found transcriptome signatures unique to each brain region that are comprise of specific cellular pathways. We also revealed that fear conditioning leads to alterations in mRNAs levels 24 h after training in hippocampal neuropil, but not in hippocampal cell layers or BLA. The two main groups of altered mRNAs encode proteins involved in neuronal transmission, neuronal morphogenesis and neuronal development and the vast majority are known to be enriched in neurons. None of these mRNAs levels were altered by fear conditioning in EphB2lacZ/lacZ mice, which were also impaired in long-term fear memory. We show here that fear conditioning leads to an enduring alteration in mRNAs levels in hippocampal neuropil that is dependent on processes mediated by EphB2 that are needed for long-term memory formation.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Israel Science Foundation for their support of this study.

Funding

This work was supported by the Israel Science Foundation grant to RL.

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Authors and Affiliations

  1. Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel

    Subhajit Jana, Monica Dines & Raphael Lamprecht

  2. Bioinformatics Service Unit, University of Haifa, Haifa, Israel

    Maya Lalzar

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  1. Subhajit Jana
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  2. Monica Dines
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  3. Maya Lalzar
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  4. Raphael Lamprecht
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Contributions

Experiments were performed by Subhajit Jana with the help of Monica Dines. Behavioral data was analyzed by Subhajit Jana and Raphael Lamprecht. Gene expression data were analyzed by Maya Lalzar. The first draft of the manuscript was written by Raphael Lamprecht. All authors contributed in editing the manuscript and read and approved the manuscript.

Corresponding author

Correspondence to Raphael Lamprecht.

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Behavioral experiments were approved by the University of Haifa Institutional Committee for animal experiments in accordance with National Institutes of Health guidelines.

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Jana, S., Dines, M., Lalzar, M. et al. Fear Conditioning Leads to Enduring Alterations in RNA Transcripts in Hippocampal Neuropil that are Dependent on EphB2 Forward Signaling. Mol Neurobiol 60, 2320–2329 (2023). https://doi.org/10.1007/s12035-022-03191-w

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