Skip to main content

Umbrella menu

  • SfN.org
  • eNeuro
  • The Journal of Neuroscience
  • Neuronline
  • BrainFacts.org

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Latest Articles
    • Issue Archive
    • Editorials
    • Research Highlights
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • EDITORIAL BOARD
  • BLOG
  • ABOUT
    • Overview
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
  • SfN.org
  • eNeuro
  • The Journal of Neuroscience
  • Neuronline
  • BrainFacts.org

User menu

  • My alerts

Search

  • Advanced search
eNeuro
  • My alerts

eNeuro

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Latest Articles
    • Issue Archive
    • Editorials
    • Research Highlights
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • EDITORIAL BOARD
  • BLOG
  • ABOUT
    • Overview
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
PreviousNext
Research ArticleResearch Article: New Research, Cognition and Behavior

Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice

Dirk-Jan Saaltink, Erik W. van Zwet and Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: https://doi.org/10.1523/ENEURO.0324-19.2020
Dirk-Jan Saaltink
1Department of Cell and Chemical Biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erik W. van Zwet
2Department of Biomedical Data Sciences, 2333ZA Leiden University Medical Center, Leiden, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erno Vreugdenhil
1Department of Cell and Chemical Biology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Figure1
    • Download figure
    • Open in new tab
    • Download powerpoint
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    Specific knock-down of DCLK1 splice variant DCL. A, Overview of the three most important DCLK1 splice variants and their functional components. The shRNA target sequence resides in the 3′-UTR of DCL mRNA which is absent in DCLK-long and DCLK-short. B, Western blot analysis reveals splice variant specific knock-down of DCL in dox-induced transgenic (TG) animals compared with dox-induced WT animals. DCLK-long and DCLK-short expression is not affected. C, Although there is some leakage, this leakage does not affect hippocampal DCL expression during embryonic development. There is no significant difference in DCL expression between non-induced WT and TG littermates at embryonic day (ED)14 and postnatal day (PND)1 and PND3. D, After dox induction, in the hippocampal tissue (Hi) an almost 10-fold higher shRNA expression measured compared with non-induced TG littermates (Student’s t test, n = 4, two-tailed, p < 0.0001) In the OB a nearly 25-fold higher shRNA expression is measured (Student’s t test, n = 4, two-tailed, p < 0.0001). E, In both hippocampus (Hi, Student’s t test, two-tailed, control n = 4, dox n = 5, p < 0.01) and OB (Student’s t test, two-tailed, control n = 4, dox n = 5, p < 0.0001), DCL protein expression is reduced to 25% after dox induction compared with non-induced TG littermates.

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Adult neurogenesis measurement using BrdU labeling. A, Twenty-four hours after a single BrdU injection, a significant (two-way ANOVA, F(3) = 6.079, p = 0.004) with an significant interaction between genotype and diet (p = 0.043). The number of BrdU+ cells is significantly increased compared with WT animals on dox diet and DCL-KD and WT mice on control diets (respectively, p = 0.0056, p = 0.0022, and p = 0.0017; n = 6). Effect of dox on DCL-KD mice: 95% CI: 401.7, 1573; p = 0.0022). B, Examples of hippocampi derived from animals killed 24 h after BrdU injection. Both sections are stained for BrdU and show mainly BrdU+ cells in the SGZ. Tissue is derived from dox-induced transgenic animals (dox) and non-induced transgenic littermates (control) C, BrdU/NeuN double staining revealed a trend (F(3) = 2.77, p = 0.057, two-way ANOVA) in double-positive cells in hippocampal dentate gyrus of dox-induced transgenic animals (dox, n = 5) compared with non-induced transgenic littermates and both WT control groups (control, n = 4). In the dox-fed group, pairwise comparison using t tests with pooled SD shows a significant difference between DCL-KD and WT animals (p = 0.01). Effect of dox on DCL-KD mice: 95% CI: −323.7, 68.6; p = 0.188. D–F, Confocal laser scanning microscopy images showing co localization of BrdU (green in D) and NeuN (red in E). Only cells in the dentate gyrus who are double-positive (yellow in F) were counted. Scale bar in D–F: 25 μm. Significant differences are indicated with an asterisk. Means are indicated with a black bar.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    DCX cell morphology. A, DCX-expressing cells in the hippocampal dentate gyrus of a transgenic animal on a control diet showing a normal DCX morphology with cell nuclei close to the SGZ and dendrites toward the molecular layer (ML). B, Hippocampal dentate gyrus of a dox-induced transgenic littermate showing aberrant morphology of DCX+ cells. Hardly any DCX+ cell has dendrites in the granular cell layer (GCL) or ML. C, D, Close-up of DCX-expressing cells in the hippocampal dentate gyrus of a transgenic animal on a control diet (C). Several DCX+ cells show dendritic outgrow (arrows) toward the ML which are absent after DCL-KD (D). E–G, Number of proliferating type 1, 2, and 3 DCX+ cells in transgenic and WT mice on a control or dox diet. Two-way ANOVA testing shows a significant effect in the type 1 and 3 DCX+ cells (respectively, F(3) = 3.377, p = 0.04, and F(3) = 3.473, p = 0.04). Effect of dox on DCL-KD mice: 95% CI type 1 cells: 157.0, 5501.8; p = 0.039; 95% CI type 2 cells: −3553.7, 164.5; p = 0.072; 95% CI type 3 cells: −665.5, −12.8; p = 0.042. Significant differences are indicated with an asterisk. Means are indicated with a black bar. For further details, see main text.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    Setup of the CHB experiment. A, Animals were put on a dox diet for at least five weeks before the CHB was started. B, The CHB paradigm started with a FET. Seven days later, the animals followed a training for four consecutive days with two trials a day. At day 5, the animals were exposed to a probe trial in which the escape hole was closed. C, The hole board was equipped with 12 holes. During training, one hole (black), by which animals could reach their home cage, was open. D, Photograph of the CHB setup in the lab.

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5.

    Spatial parameters measured on the CHB. A, First visit latency. All four groups showed a similar decrease over four training days in latency to target (two-way ANOVA for repeated-measures, F(3) = 39 521, p < 0.001). B, Probe trial. DCL knock-down had no effect on the parameters “latency to target” (two-way ANOVA F(1) = 0.744, p = 0.392). C, Errors to target. All four groups showed a similar decrease over four training days in errors to target (two-way ANOVA for repeated-measures, F(3) = 13.230, p < 0.001). D, Probe trial. DCL-KD had no effect on the parameters “errors to target” (two-way ANOVA, F(1) = 2222, p = 0.141). For further details, see main text.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6.

    Motivational parameters measured on the CHB. A, DCL-KD animals showed a significant longer escape latency at each first test of the new day (T3, T5, and T7, one-way ANOVA, F(3) = 12.574, p < 0.005). B, Percent of animals who did not reach the target within 120 s. C, Mean distance moved during each trial. DCL-KD animals move a significant longer distance (two-way ANOVA F(1) = 4.366, p = 0.041). D, Average velocity during each trial. DCL-KD animals are significant slower compared with DCL+ animals and WT controls (GML, F(1) = 15.101, p = 0.001).

Back to top

In this issue

eneuro: 7 (5)
eNeuro
Vol. 7, Issue 5
September/October 2020
  • Table of Contents
  • Index by author
Email

Thank you for sharing this eNeuro article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice
(Your Name) has forwarded a page to you from eNeuro
(Your Name) thought you would be interested in this article in eNeuro.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice
Dirk-Jan Saaltink, Erik W. van Zwet, Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: 10.1523/ENEURO.0324-19.2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Share
Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice
Dirk-Jan Saaltink, Erik W. van Zwet, Erno Vreugdenhil
eNeuro 29 September 2020, 7 (5) ENEURO.0324-19.2020; DOI: 10.1523/ENEURO.0324-19.2020
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Significance Statement
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
    • Synthesis
    • Author Response
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • cognition
  • DCLK1
  • doublecortin
  • hippocampus
  • neurogenesis
  • RNA interference

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

Research Article: New Research

  • Differential Impact of Inhibitory G-Protein Signaling Pathways in Ventral Tegmental Area Dopamine Neurons on Behavioral Sensitivity to Cocaine and Morphine
  • Activation of Transient Receptor Potential Vanilloid 1 Channels in the Nucleus of the Solitary Tract and Activation of Dynorphin Input to the Median Preoptic Nucleus Contribute to Impaired BAT Thermogenesis in Diet-Induced Obesity
  • The Substantia Nigra Pars Reticulata Modulates Error-Based Saccadic Learning in Monkeys
Show more Research Article: New Research

Cognition and Behavior

  • Differential Impact of Inhibitory G-Protein Signaling Pathways in Ventral Tegmental Area Dopamine Neurons on Behavioral Sensitivity to Cocaine and Morphine
  • Activation of Transient Receptor Potential Vanilloid 1 Channels in the Nucleus of the Solitary Tract and Activation of Dynorphin Input to the Median Preoptic Nucleus Contribute to Impaired BAT Thermogenesis in Diet-Induced Obesity
  • The Substantia Nigra Pars Reticulata Modulates Error-Based Saccadic Learning in Monkeys
Show more Cognition and Behavior

Subjects

  • Cognition and Behavior
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Latest Articles
  • Issue Archive
  • Blog
  • Browse by Topic

Information

  • For Authors
  • For the Media

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
  • Feedback
(eNeuro logo)
(SfN logo)

Copyright © 2021 by the Society for Neuroscience.
eNeuro eISSN: 2373-2822

The ideas and opinions expressed in eNeuro do not necessarily reflect those of SfN or the eNeuro Editorial Board. Publication of an advertisement or other product mention in eNeuro should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in eNeuro.