Fig. 2.

Ketamine rapidly increases synaptic proteins and spine number. (A) Time course for ketamine (10 mg/kg, ip) induction of synaptic proteins ARC, synapsin I, PSD95, and GluR1 in synaptoneurosomes of prefrontal cortex (PFC), and (B) blockade by pre-treatment (30 min) with a selective mTOR inhibitor rapamycin (0.2 nmol, ICV) (values represent mean ± SEM, n = 4 – 6 animals; *P < 0.05; **P < 0.01, ANOVA.) (C) Ketamine increased spine density in medial PFC, analyzed by two-photon microscopy 24 hr after treatment. Representative images are shown of high magnification Z-stack projections of apical tuft segments of Neurobiotin-labeled layer V pyramidal cells (Scale: 5 μm). (D) Results are the mean ± SEM (8 cells from 4 rats in each group; *P < 0.05; **P < 0.01, t-test). (E) Ketamine enhanced mPFC layer V pyramidal cell EPSC responses. Sample whole cell voltage-clamp recordings of 5-HT and hypocretin-induced EPSCs in slices (24 hr post-ketamine). (F) Cumulative probability distributions showing significant increases in amplitude (p < 0.0001, KS-z vale = 6.5 for 5-HT and 6.7 for Hcrt) and (H) frequency of 5-HT- and hypocretin-induced EPSCs (n = 12 neurons/group; *P < 0.05, t-test). Ketamine-induction of spine density and function were blocked by rapamycin infusions (C–G)