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Articles, Development/Plasticity/Repair

Subcortical Glutamate Mediates the Reduction of Short-Range Functional Connectivity with Age in a Developmental Cohort

Carmen Ghisleni, Steffen Bollmann, Simon-Shlomo Poil, Daniel Brandeis, Ernst Martin, Lars Michels, Ruth L. O'Gorman and Peter Klaver
Journal of Neuroscience 3 June 2015, 35 (22) 8433-8441; DOI: https://doi.org/10.1523/JNEUROSCI.4375-14.2015
Carmen Ghisleni
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
3Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland,
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Steffen Bollmann
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
3Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland,
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Simon-Shlomo Poil
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
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Daniel Brandeis
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
3Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland,
5Department of Child and Adolescent Psychiatry, University of Zurich, 8032 Zurich, Switzerland,
6Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/ Heidelberg University, 68159 Mannheim, Germany, and
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Ernst Martin
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
3Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland,
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Lars Michels
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
7Neuroradiology Clinic, University Hospital Zurich, 8091 Zurich, Switzerland
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Ruth L. O'Gorman
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
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Peter Klaver
1Center for MR-Research, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland,
2Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zürich, Switzerland,
3Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland,
4Department of Psychology, University of Zurich, 8050 Zurich, Switzerland,
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Abstract

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.

  • development
  • functional connectivity
  • GABA
  • glutamate
  • magnetic resonance spectroscopy
  • working memory
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The Journal of Neuroscience: 35 (22)
Journal of Neuroscience
Vol. 35, Issue 22
3 Jun 2015
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Subcortical Glutamate Mediates the Reduction of Short-Range Functional Connectivity with Age in a Developmental Cohort
Carmen Ghisleni, Steffen Bollmann, Simon-Shlomo Poil, Daniel Brandeis, Ernst Martin, Lars Michels, Ruth L. O'Gorman, Peter Klaver
Journal of Neuroscience 3 June 2015, 35 (22) 8433-8441; DOI: 10.1523/JNEUROSCI.4375-14.2015

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Subcortical Glutamate Mediates the Reduction of Short-Range Functional Connectivity with Age in a Developmental Cohort
Carmen Ghisleni, Steffen Bollmann, Simon-Shlomo Poil, Daniel Brandeis, Ernst Martin, Lars Michels, Ruth L. O'Gorman, Peter Klaver
Journal of Neuroscience 3 June 2015, 35 (22) 8433-8441; DOI: 10.1523/JNEUROSCI.4375-14.2015
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Keywords

  • development
  • functional connectivity
  • GABA
  • glutamate
  • magnetic resonance spectroscopy
  • working memory

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