Dataset Information

Analysis of hippocampal-dependent learning and memory behaviour in mice lacking Nfix from adult neural stem cells.

ABSTRACT:

Objective

The active place avoidance task (APA) is a behavioural task used to assess learning and memory in rodents. This task relies on the hippocampus, a region of the cerebral cortex capable of generating new neurons from neural stem cells. In this study, to gain further insight into the behavioural phenotype of mice deficient in the transcription factor Nfix, a gene expressed by adult neural stem cells, we examined learning and memory parameters from the APA task that were not published in our original investigation. We analysed time to first and second shock, maximum path and time of shock avoidance, number of entries into the shock zone and time spent in the shock zone. We also assessed performance in the APA task based on sex.

Results

We found mice deficient in Nfix displayed decreased latency to second shock compared to the control mice. Nfix deficient mice entered the shock zone more frequently and also spent more time in the shock zone. Our data provides further insights into the memory deficits evident in Nfix mutant mice, indicating these mice have a memory retrieval problem and may employ a different navigation strategy in the APA task.

SUBMITTER: Zalucki O

PROVIDER: S-EPMC6080370 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Analysis of hippocampal-dependent learning and memory behaviour in mice lacking Nfix from adult neural stem cells.

Zalucki Oressia O Harkins Danyon D Harris Lachlan L Burne Thomas H J THJ Gronostajski Richard M RM Piper Michael M

BMC research notes 20180806 1

<h4>Objective</h4>The active place avoidance task (APA) is a behavioural task used to assess learning and memory in rodents. This task relies on the hippocampus, a region of the cerebral cortex capable of generating new neurons from neural stem cells. In this study, to gain further insight into the behavioural phenotype of mice deficient in the transcription factor Nfix, a gene expressed by adult neural stem cells, we examined learning and memory parameters from the APA task that were not publis ...[more]

PMID: 30081965

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Project description:Stem cells in adult mammalian tissues are held in a reversible resting state, known as quiescence, for prolonged periods of time. Recent studies have greatly increased our understanding of the epigenetic and transcriptional landscapes that underlie stem cell quiescence. However, the transcription factor code that actively maintains the quiescence program remains poorly defined. Similarly, alternative splicing events affecting transcription factors in stem cell quiescence have been overlooked. Here we show that the transcription factor T-cell factor/lymphoid enhancer factor LEF1, a central player in canonical β-catenin-dependent Wnt signalling, undergoes alternative splicing and switches isoforms in quiescent neural stem cells. We found that active β-catenin and its partner LEF1 accumulated in quiescent hippocampal neural stem and progenitor cell (Q-NSPC) cultures. Accordingly, Q-NSPCs showed enhanced TCF/LEF1-driven transcription and a basal Wnt activity that conferred a functional advantage to the cultured cells in a Wnt-dependent assay. At a mechanistic level, we found a fine regulation of Lef1 gene expression. The coordinate upregulation of Lef1 transcription and retention of alternative spliced exon 6 (E6) led to the accumulation of a full-length protein isoform (LEF1-FL) that displayed increased stability in the quiescent state. Prospectively isolated GLAST + cells from the postnatal hippocampus also underwent E6 retention at the time quiescence is established in vivo. Interestingly, LEF1 motif was enriched in quiescence-associated enhancers of genes upregulated in Q-NSPCs and quiescence-related NFIX transcription factor motifs flanked the LEF1 binding sites. We further show that LEF1 interacts with NFIX and identify putative LEF1/NFIX targets. Together, our results uncover an unexpected role for LEF1 in gene regulation in quiescent NSPCs, and highlight alternative splicing as a post-transcriptional regulatory mechanism in the transition from stem cell activation to quiescence.

Project description:Over the last years, the SWATH data-independent acquisition protocol (Sequential Window acquisition of All THeoretical mass spectra) has become a cornerstone for the worldwide proteomics community (Collins et al., 2017) [1]. In this approach, a high-resolution quadrupole-ToF mass spectrometer acquires thousands of MS/MS data by selecting not just a single precursor at a time, but by allowing a broad m/z range to be fragmented. This acquisition window is then sequentially moved from the lowest to the highest mass selection range. This technique enables the acquisition of thousands of high-resolution MS/MS spectra per minute in a standard LC-MS run. In the subsequent data analysis phase, the corresponding dataset is searched in a "triple quadrupole-like" mode, thus not considering the whole MS/MS scan spectrum, but by searching for several precursor to fragment transitions that identify and quantify the corresponding peptide. This search is made possible with the use of an ion library, previously acquired in a classical data dependent, full-spectrum mode (Fabre et al., 2017; Wu et al., 2017) [2], [3]. The SWATH protocol, combining the protein identification power of high-resolution MS/MS spectra with the robustness and accuracy in analyte quantification of triple-quad targeted workflows, has become very popular in proteomics research. The major drawback lies in the ion library itself, which is normally demanding and time-consuming to build. Conversely, through the realignment of chromatographic retention times, an ion library of a given proteome can relatively easily be tailored upon "any" proteomics experiment done on the same proteome. We are thus hereby sharing with the worldwide proteomics community our newly acquired ion library of mouse adult hippocampal neural stem cells. Given the growing effort in neuroscience research involving proteomics experiments (Pons-Espinal et al., 2017; Sarnyai and Guest, 2017; Sethi et al., 2015; Bramini et al., 2016) [4,[5], [6], [7], we believe that this data might be of great help for the neuroscience community. All the here reported data (RAW files, results and ion library) can be freely downloaded from the SWATHATLAS (Deutsch et al., 2008) [8] website (http://www.peptideatlas.org/PASS/PASS01110).

Dataset Information

Analysis of hippocampal-dependent learning and memory behaviour in mice lacking Nfix from adult neural stem cells.

Objective

Results

Publications

Analysis of hippocampal-dependent learning and memory behaviour in mice lacking Nfix from adult neural stem cells.

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