GABA-A receptor-dependent mechanisms prevent excessive spine elimination during postnatal maturation of the mouse cortex in vivo

•Elimination of pre-existing spines is modulated extensively in postnatal mouse cortex.•Decreased spine elimination decelerates net spine loss rate ~6-fold starting at ~4months of age.•Bicuculline blockade of GABA-A receptors enhances spine elimination but not spine formation.•Enhancement of spine e...

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Veröffentlicht in:FEBS letters 2014-12, Vol.588 (24), p.4551-4560
1. Verfasser: Chen, Yachi
Format: Artikel
Sprache:eng
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Zusammenfassung:•Elimination of pre-existing spines is modulated extensively in postnatal mouse cortex.•Decreased spine elimination decelerates net spine loss rate ~6-fold starting at ~4months of age.•Bicuculline blockade of GABA-A receptors enhances spine elimination but not spine formation.•Enhancement of spine elimination is reversible upon cessation of bicuculline treatment.•GABA-A receptor blockade enhances spine elimination at multiple postnatal developmental stages. Dendritic spine dynamics are implicated in the structural plasticity of cognition-related neuroconnectivity. This study utilized the transcranial in vivo imaging approach to investigate spine dynamics in intact brains of living yellow fluorescent protein-expressing mice. A developmental switch in the net spine loss rate occurred at ∼4months of age. The initially rapid rate slowed down ∼6-fold due to substantially reduced spine elimination with minor changes in formation. Furthermore, pharmacological blockade of γ-aminobutyric acid type A (GABA-A) receptors resulted in significantly increased elimination of pre-existing spines without affecting new spine formation. Spine elimination returned to normal levels following treatment cessation. Thus, GABA-A receptor-dependent mechanisms act as “brakes” – keeping spine elimination in check to prevent over-pruning, thereby preserving the integrity of cognition-related cortical circuits.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2014.10.023