Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection

II. Genetic covariation and identification of Nos1 as linking candidate gene

Julia Krebs, Benedikt Römer, Rupert W. Overall, Klaus Fabel, Harish Babu, Moritz D. Brandt, Robert Williams, Sebastian Jessberger, Gerd Kempermann

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The hippocampus of adult rodents harbors two systems exhibiting structural plasticity beyond the level of synapses and dendrites. First, the persistent generation of granule cells (adult neurogenesis); second, dynamic changes in the mossy fibers (MF), in particular in the infrapyramidal mossy fiber (IMF) tract. Because MFs are the axons of granule cells, the question arises whether these two types of plasticity are linked. In the first part of this study (Römer et al., 2011) we have asked how both traits are regulated in relation to each other. In the present part, we asked whether, besides activity-dependent co-regulation, there would also be signs of genetic co-regulation and co-variance. For this purpose we used the BXD panel of recombinant inbred strains of mice, a unique genetic reference population that allows genetic association studies. In 31 BXD strains we did not find correlations between the traits describing the volume of the MF subfields and measures of adult neurogenesis. When we carried out quantitative trait locus mapping for these traits, we found that the map for IMF volume showed little overlap with the maps for the other parts of the projection or for adult neurogenesis, suggesting that to a large degree the IMF is regulated independently. The highest overlapping peak in the genome-wide association maps for IMF volume and the number of new neurons was on distal chromosome 5 (118.3-199.2 Mb) with an LRS score of 5.5 for IMF and 6.0 for new neurons. Within this interval we identified Nos1 (neuronal nitric oxide synthase) as a cis-acting (i.e., presumably autoregulatory) candidate gene. The expression of Nos1 is has been previously linked with both IMF and adult neurogenesis, supporting our findings. Despite explaining on its own very little of the variance in the highly multigenic traits studied, our results suggest Nos1 may play a part in the complex genetic control of adult neurogenesis and IMF morphology.

Original languageEnglish (US)
Article numberArticle 106
JournalFrontiers in Neuroscience
Issue numberSEP
DOIs
StatePublished - Dec 1 2011

Fingerprint

Neurogenesis
Genes
Neurons
Nitric Oxide Synthase Type I
Chromosomes, Human, Pair 5
Inbred Strains Mice
Quantitative Trait Loci
Population Genetics
Genetic Association Studies
Dendrites
Synapses
Axons
Rodentia
Hippocampus
Genome

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection : II. Genetic covariation and identification of Nos1 as linking candidate gene. / Krebs, Julia; Römer, Benedikt; Overall, Rupert W.; Fabel, Klaus; Babu, Harish; Brandt, Moritz D.; Williams, Robert; Jessberger, Sebastian; Kempermann, Gerd.

In: Frontiers in Neuroscience, No. SEP, Article 106, 01.12.2011.

Research output: Contribution to journalArticle

Krebs, Julia ; Römer, Benedikt ; Overall, Rupert W. ; Fabel, Klaus ; Babu, Harish ; Brandt, Moritz D. ; Williams, Robert ; Jessberger, Sebastian ; Kempermann, Gerd. / Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection : II. Genetic covariation and identification of Nos1 as linking candidate gene. In: Frontiers in Neuroscience. 2011 ; No. SEP.
@article{9d3b17d2b0934379a61dc38608a9fc37,
title = "Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection: II. Genetic covariation and identification of Nos1 as linking candidate gene",
abstract = "The hippocampus of adult rodents harbors two systems exhibiting structural plasticity beyond the level of synapses and dendrites. First, the persistent generation of granule cells (adult neurogenesis); second, dynamic changes in the mossy fibers (MF), in particular in the infrapyramidal mossy fiber (IMF) tract. Because MFs are the axons of granule cells, the question arises whether these two types of plasticity are linked. In the first part of this study (R{\"o}mer et al., 2011) we have asked how both traits are regulated in relation to each other. In the present part, we asked whether, besides activity-dependent co-regulation, there would also be signs of genetic co-regulation and co-variance. For this purpose we used the BXD panel of recombinant inbred strains of mice, a unique genetic reference population that allows genetic association studies. In 31 BXD strains we did not find correlations between the traits describing the volume of the MF subfields and measures of adult neurogenesis. When we carried out quantitative trait locus mapping for these traits, we found that the map for IMF volume showed little overlap with the maps for the other parts of the projection or for adult neurogenesis, suggesting that to a large degree the IMF is regulated independently. The highest overlapping peak in the genome-wide association maps for IMF volume and the number of new neurons was on distal chromosome 5 (118.3-199.2 Mb) with an LRS score of 5.5 for IMF and 6.0 for new neurons. Within this interval we identified Nos1 (neuronal nitric oxide synthase) as a cis-acting (i.e., presumably autoregulatory) candidate gene. The expression of Nos1 is has been previously linked with both IMF and adult neurogenesis, supporting our findings. Despite explaining on its own very little of the variance in the highly multigenic traits studied, our results suggest Nos1 may play a part in the complex genetic control of adult neurogenesis and IMF morphology.",
author = "Julia Krebs and Benedikt R{\"o}mer and Overall, {Rupert W.} and Klaus Fabel and Harish Babu and Brandt, {Moritz D.} and Robert Williams and Sebastian Jessberger and Gerd Kempermann",
year = "2011",
month = "12",
day = "1",
doi = "10.3389/fnins.2011.00106",
language = "English (US)",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",
number = "SEP",

}

TY - JOUR

T1 - Adult hippocampal neurogenesis and plasticity in the infrapyramidal bundle of the mossy fiber projection

T2 - II. Genetic covariation and identification of Nos1 as linking candidate gene

AU - Krebs, Julia

AU - Römer, Benedikt

AU - Overall, Rupert W.

AU - Fabel, Klaus

AU - Babu, Harish

AU - Brandt, Moritz D.

AU - Williams, Robert

AU - Jessberger, Sebastian

AU - Kempermann, Gerd

PY - 2011/12/1

Y1 - 2011/12/1

N2 - The hippocampus of adult rodents harbors two systems exhibiting structural plasticity beyond the level of synapses and dendrites. First, the persistent generation of granule cells (adult neurogenesis); second, dynamic changes in the mossy fibers (MF), in particular in the infrapyramidal mossy fiber (IMF) tract. Because MFs are the axons of granule cells, the question arises whether these two types of plasticity are linked. In the first part of this study (Römer et al., 2011) we have asked how both traits are regulated in relation to each other. In the present part, we asked whether, besides activity-dependent co-regulation, there would also be signs of genetic co-regulation and co-variance. For this purpose we used the BXD panel of recombinant inbred strains of mice, a unique genetic reference population that allows genetic association studies. In 31 BXD strains we did not find correlations between the traits describing the volume of the MF subfields and measures of adult neurogenesis. When we carried out quantitative trait locus mapping for these traits, we found that the map for IMF volume showed little overlap with the maps for the other parts of the projection or for adult neurogenesis, suggesting that to a large degree the IMF is regulated independently. The highest overlapping peak in the genome-wide association maps for IMF volume and the number of new neurons was on distal chromosome 5 (118.3-199.2 Mb) with an LRS score of 5.5 for IMF and 6.0 for new neurons. Within this interval we identified Nos1 (neuronal nitric oxide synthase) as a cis-acting (i.e., presumably autoregulatory) candidate gene. The expression of Nos1 is has been previously linked with both IMF and adult neurogenesis, supporting our findings. Despite explaining on its own very little of the variance in the highly multigenic traits studied, our results suggest Nos1 may play a part in the complex genetic control of adult neurogenesis and IMF morphology.

AB - The hippocampus of adult rodents harbors two systems exhibiting structural plasticity beyond the level of synapses and dendrites. First, the persistent generation of granule cells (adult neurogenesis); second, dynamic changes in the mossy fibers (MF), in particular in the infrapyramidal mossy fiber (IMF) tract. Because MFs are the axons of granule cells, the question arises whether these two types of plasticity are linked. In the first part of this study (Römer et al., 2011) we have asked how both traits are regulated in relation to each other. In the present part, we asked whether, besides activity-dependent co-regulation, there would also be signs of genetic co-regulation and co-variance. For this purpose we used the BXD panel of recombinant inbred strains of mice, a unique genetic reference population that allows genetic association studies. In 31 BXD strains we did not find correlations between the traits describing the volume of the MF subfields and measures of adult neurogenesis. When we carried out quantitative trait locus mapping for these traits, we found that the map for IMF volume showed little overlap with the maps for the other parts of the projection or for adult neurogenesis, suggesting that to a large degree the IMF is regulated independently. The highest overlapping peak in the genome-wide association maps for IMF volume and the number of new neurons was on distal chromosome 5 (118.3-199.2 Mb) with an LRS score of 5.5 for IMF and 6.0 for new neurons. Within this interval we identified Nos1 (neuronal nitric oxide synthase) as a cis-acting (i.e., presumably autoregulatory) candidate gene. The expression of Nos1 is has been previously linked with both IMF and adult neurogenesis, supporting our findings. Despite explaining on its own very little of the variance in the highly multigenic traits studied, our results suggest Nos1 may play a part in the complex genetic control of adult neurogenesis and IMF morphology.

UR - http://www.scopus.com/inward/record.url?scp=84859582768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859582768&partnerID=8YFLogxK

U2 - 10.3389/fnins.2011.00106

DO - 10.3389/fnins.2011.00106

M3 - Article

JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

SN - 1662-4548

IS - SEP

M1 - Article 106

ER -