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Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus.

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Title: Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus.
Authors: Marshall, Pepin (AUTHOR), Garton, Daniel R. (AUTHOR), Taira, Tomi (AUTHOR), Võikar, Vootele (AUTHOR), Vilenius, Carolina (AUTHOR), Kulesskaya, Natalia (AUTHOR), Rivera, Claudio (AUTHOR), Andressoo, Jaan‐Olle (AUTHOR)
Source: European Journal of Neuroscience. Apr2021, Vol. 53 Issue 8, p2469-2482. 14p. 4 Graphs.
Subjects: Glial cell line-derived neurotrophic factor, Spatial memory, Maze tests, Hippocampus (Brain), Long-term memory
Abstract: Parvalbumin‐positive interneurons (PV+) are a key component of inhibitory networks in the brain and are known to modulate memory and learning by shaping network activity. The mechanisms of PV+ neuron generation and maintenance are not fully understood, yet current evidence suggests that signalling via the glial cell line‐derived neurotrophic factor (GDNF) receptor GFRα1 positively modulates the migration and differentiation of PV+ interneurons in the cortex. Whether GDNF also regulates PV+ cells in the hippocampus is currently unknown. In this study, we utilized a Gdnf "hypermorph" mouse model where GDNF is overexpressed from the native gene locus, providing greatly increased spatial and temporal specificity of protein expression over established models of ectopic expression. Gdnfwt/hyper mice demonstrated impairments in long‐term memory performance in the Morris water maze test and an increase in inhibitory tone in the hippocampus measured electrophysiologically in acute brain slice preparations. Increased PV+ cell number was confirmed immunohistochemically in the hippocampus and in discrete cortical areas and an increase in epileptic seizure threshold was observed in vivo. The data consolidate prior evidence for the actions of GDNF as a regulator of PV+ cell development in the cortex and demonstrate functional effects upon network excitability via modulation of functional GABAergic signalling and under epileptic challenge. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus.
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  Data: <searchLink fieldCode="AR" term="%22Marshall%2C+Pepin%22">Marshall, Pepin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Garton%2C+Daniel+R%2E%22">Garton, Daniel R.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Taira%2C+Tomi%22">Taira, Tomi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Võikar%2C+Vootele%22">Võikar, Vootele</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vilenius%2C+Carolina%22">Vilenius, Carolina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kulesskaya%2C+Natalia%22">Kulesskaya, Natalia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rivera%2C+Claudio%22">Rivera, Claudio</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Andressoo%2C+Jaan‐Olle%22">Andressoo, Jaan‐Olle</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Apr2021, Vol. 53 Issue 8, p2469-2482. 14p. 4 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Glial+cell+line-derived+neurotrophic+factor%22">Glial cell line-derived neurotrophic factor</searchLink><br /><searchLink fieldCode="DE" term="%22Spatial+memory%22">Spatial memory</searchLink><br /><searchLink fieldCode="DE" term="%22Maze+tests%22">Maze tests</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Long-term+memory%22">Long-term memory</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Parvalbumin‐positive interneurons (PV+) are a key component of inhibitory networks in the brain and are known to modulate memory and learning by shaping network activity. The mechanisms of PV+ neuron generation and maintenance are not fully understood, yet current evidence suggests that signalling via the glial cell line‐derived neurotrophic factor (GDNF) receptor GFRα1 positively modulates the migration and differentiation of PV+ interneurons in the cortex. Whether GDNF also regulates PV+ cells in the hippocampus is currently unknown. In this study, we utilized a Gdnf "hypermorph" mouse model where GDNF is overexpressed from the native gene locus, providing greatly increased spatial and temporal specificity of protein expression over established models of ectopic expression. Gdnfwt/hyper mice demonstrated impairments in long‐term memory performance in the Morris water maze test and an increase in inhibitory tone in the hippocampus measured electrophysiologically in acute brain slice preparations. Increased PV+ cell number was confirmed immunohistochemically in the hippocampus and in discrete cortical areas and an increase in epileptic seizure threshold was observed in vivo. The data consolidate prior evidence for the actions of GDNF as a regulator of PV+ cell development in the cortex and demonstrate functional effects upon network excitability via modulation of functional GABAergic signalling and under epileptic challenge. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ejn.15126
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      – Code: eng
        Text: English
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        PageCount: 14
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      – SubjectFull: Glial cell line-derived neurotrophic factor
        Type: general
      – SubjectFull: Spatial memory
        Type: general
      – SubjectFull: Maze tests
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      – SubjectFull: Hippocampus (Brain)
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      – SubjectFull: Long-term memory
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      – TitleFull: Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus.
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              Text: Apr2021
              Type: published
              Y: 2021
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