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

Abstract

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.