Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation
Science April 12, 2019 R. N. Moda-Sava, Mitchell H. Murdock, P. Parekh et al.
Ketamine rescues depression-like behavior in mice by reversing stress-induced loss of dendritic spines and restoring coordinated neural activity in the prefrontal cortex. Spine formation in this brain region is necessary for sustaining—but not for initially inducing—ketamine's antidepressant effects on motivated escape behavior. Optogenetically deleting newly formed spines eliminated the long-term behavioral benefits, while deleting random spines did not. The findings suggest that interventions aimed at preserving restored synapses could help maintain remission from depression.