PA enhances network activity via increases in excitatory neurotransmission. A, Cell attached recordings of hippocampal neurons in dissociated cultured treated with vehicle or PA (100 μm, 45 min). Inset: enlarged region of recording (red box) showing individual spikes in a burst. B, C, Cumulative histogram of amplitude (pA) and interevent interval (msec) of mEPSCs recorded from neurons treated with vehicle or 100 μm PA for 45 or 90 min. Inset, mean (+ SEM) mEPSC amplitude and frequency in neurons after treatment with PA (100 μm) or vehicle. *p < 0.5 compared to vehicle treated controls. D, Representative recordings in neurons treated with PA (100 mm, 45 min) with or without 30 min pretreatment with rapamycin (200 nm), anisomysin (40 μm) or TrkB-fc (1 μg/ml). E, Time course of mean (+SEM) mEPSC amplitude and frequency of spontaneous mEPSCs at 45 m or 90 m exposure to PA with or without pretreatment, as indicated above. Sample sizes for the indicated groups: Vehicle (n = 7), PA 45 min (n = 9), PA45 min + rapamycin (n = 9), PA45 min + anisomycin (n = 5), PA45 min +TrKB-fc (n = 6), PA90 min (n = 6), PA90 min + rapamycin (n = 6), PA90 min + anisomycin (n = 9), PA90 min+ TrkBfc (n = 3), rapamycin alone (n = 7), anisomycin alone (n = 7), TrkB-fc alone (n = 6). Acute activation of mTORC1 signaling with PA enhances mEPSC frequency in a protein synthesis, mTORC1, and TrkB-dependent manner. F, Representative recordings of pharmacologically isolated (TTX 1 μm, CNQX 10 μm, APV 50 μm) spontaneous miniature inhibitory currents (mIPSCs) in cells treated with vehicle or PA. G, Mean (+SEM) mIPSC amplitude and frequency of cultured neurons treated with vehicle or PA (100 μm, 45 min). mIPSC control, n = 16; PA 45 min, n = 20. ns=not significant. H, Whole-cell current-clamp recordings showing example action potential traces from vehicle-treated control neurons (black) or cell treated with PA (red,). APs were evoked by injecting 1 s depolarizing current steps in the presence of excitatory and inhibitory synaptic blockers (CNQX 10 μm, APV 50 μm, Bicuculine 10 μm). I, J, Mean (± SEM) and maximum number of action potentials evoked by a series of depolarizing current steps in vehicle-treated (n = 14) or PA-treated (n = 12) cells. K, Box plots showing measures of capacitance (top) and resistance (bottom) for groups as indicated.