Genetic ablation of neural progenitor cells impairs acquisition of trace eyeblink conditioning

Lisa N. Miller*, Craig Weiss, John F. Disterhoft

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adult-born neurons are believed to play a role in memory formation by providing enhanced plasticity to the hippocampus. Past studies have demonstrated that reduction of neurogenesis impairs associative learning, but these experiments used irradiation or neurotoxic substances, which may have had unintended off-target effects. Therefore, to investigate the role of these adult-born neurons more precisely, we used nestin-HSV-TK transgenic mice (Nes-TK) to selectively ablate newborn neurons. Nes-TK mice were fed a chow infused with valganciclovir to induce the ablation of neural progenitor cells. After being on this diet for 4 weeks, mice were trained on trace eyeblink conditioning, a hippocampus-dependent temporal associative memory task. Following the completion of training, brain sections from these animals were stained for doublecortin, a marker for immature neurons, to quantify levels of neurogenesis. We found that male transgenic mice on valganciclovir had significantly decreased amounts of doublecortin relative to male control animals, indicating a successful reduction in levels of neurogenesis. In conjunction with this reduction in neurogenesis, the male transgenic mice on valganciclovir learned at a significantly slower rate than male control mice. The female Nes-TK mice on valganciclovir showed no significant decrease in neurogenesis and no behavioral impairment relative to female control mice. Ultimately, the results are consistent with, and expand upon, prior studies that demonstrated that adult-born neurons are involved in the formation of associative memories. This study also provides a foundation to continue to explore the physiological role of newborn neurons with in vivo recordings during behavioral training.

Original languageEnglish (US)
Article numberENEURO.0251-19.2019
JournaleNeuro
Volume6
Issue number5
DOIs
StatePublished - Sep 1 2019

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Neurogenesis
Stem Cells
Transgenic Mice
Neurons
Nestin
Hippocampus
Conditioning (Psychology)
Learning
Diet
valganciclovir
Brain

Keywords

  • Dentate gyrus
  • Learning
  • Memory
  • Neurogenesis
  • Trace eyeblink conditioning

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Genetic ablation of neural progenitor cells impairs acquisition of trace eyeblink conditioning",
abstract = "Adult-born neurons are believed to play a role in memory formation by providing enhanced plasticity to the hippocampus. Past studies have demonstrated that reduction of neurogenesis impairs associative learning, but these experiments used irradiation or neurotoxic substances, which may have had unintended off-target effects. Therefore, to investigate the role of these adult-born neurons more precisely, we used nestin-HSV-TK transgenic mice (Nes-TK) to selectively ablate newborn neurons. Nes-TK mice were fed a chow infused with valganciclovir to induce the ablation of neural progenitor cells. After being on this diet for 4 weeks, mice were trained on trace eyeblink conditioning, a hippocampus-dependent temporal associative memory task. Following the completion of training, brain sections from these animals were stained for doublecortin, a marker for immature neurons, to quantify levels of neurogenesis. We found that male transgenic mice on valganciclovir had significantly decreased amounts of doublecortin relative to male control animals, indicating a successful reduction in levels of neurogenesis. In conjunction with this reduction in neurogenesis, the male transgenic mice on valganciclovir learned at a significantly slower rate than male control mice. The female Nes-TK mice on valganciclovir showed no significant decrease in neurogenesis and no behavioral impairment relative to female control mice. Ultimately, the results are consistent with, and expand upon, prior studies that demonstrated that adult-born neurons are involved in the formation of associative memories. This study also provides a foundation to continue to explore the physiological role of newborn neurons with in vivo recordings during behavioral training.",
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Genetic ablation of neural progenitor cells impairs acquisition of trace eyeblink conditioning. / Miller, Lisa N.; Weiss, Craig; Disterhoft, John F.

In: eNeuro, Vol. 6, No. 5, ENEURO.0251-19.2019, 01.09.2019.

Research output: Contribution to journalArticle

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AU - Weiss, Craig

AU - Disterhoft, John F.

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