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 ∼4 months 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.