Electrical stimulation of septohippocampal fibers induced fast-onset glutamatergic responses in CA3 pyramidal cells. Electrical stimulation of septohippocampal fibers induced fast-onset glutamatergic responses in CA3 pyramidal cells. Ai, The septohippocampal preparation containing a hemiseptum, ipsilateral hippocampus, and intact fornix-fimbria pathway was cut at an angle to reveal the CA3 pyramidal layer and placed in the recording chamber as shown. A stimulating electrode was positioned on the septal side of the fornix and CA3 pyramidal cells were recorded using a patch pipette. Aii, Aiii, CA3 pyramidal cells were identified by their location (Aiii) and electrophysiological criteria (Aii) (calibration: 20 mV, 250 ms). Bi, At −45 mV, in most cases fornix stimulation led to both an early-onset EPSP (inset) and a late-onset IPSP. Applying bicuculline (5 μm) revealed a potent EPSP that could depolarize some pyramidal cells to spike threshold (right). Bii, Some pyramidal cells responded with only the late-onset IPSP that was blocked by bicuculline. C, In those cells displaying both EPSP and IPSP, bicuculline was applied to isolate the EPSP and this component was subtracted from control to calculate the “IPSP” component. D, Examination of the onset latencies for EPSPs, calculated IPSPs, versus actual IPSPs indicates that the EPSPs occurred with a significantly faster onset compared with the other responses (p < 0.0001). Numbers in brackets indicate number of cells. E, F, The EPSP was mediated by glutamate as it was completely blocked by 20 μm DNQX (E), and repeated stimuli at 5 Hz could evoke rhythmic EPSPs (F). Calibration, unless otherwise noted: 2 mV, 50 ms. a.c., Anterior commissure. Carey Y. L. Huh et al. J. Neurosci. 2010;30:15951-15961 ©2010 by Society for Neuroscience