Closed-loop stimulation responses. (A) Biphasic current-controlled stimuli (cathodic, negative phase first; 400 μs per phase) were delivered to an electrode in CA1 of the hippocampus, and responses were recorded as seen here in CA3. Ten trials of every stimulus amplitude are overlaid in each panel. Stimulus duration is indicated by the red bar. The first action potentials appear at a certain stimulus threshold (≥6 μA, blue arrow), with the latency decreasing as current is increased (green arrowhead). Additional, less consistent action potentials are recruited at high stimulation intensities (purple asterisks). All traces were digitally filtered with the SALPA algorithm (Wagenaar and Potter, 2002). Stimuli were delivered at 1 Hz and in random order (to guard against neural adaptation). (B) The LFP of an electrode in CA3 was monitored for interictal spikes (IISs) and a single 10 μA biphasic current-controlled pulse was delivered to one microelectrode upon IIS detection (red X's in bottom panel). The displayed LFP trace (top panel) is from one electrode of an array implanted in CA1. The large amplitude is typical of LFPs during IISs and seizures. (C) A raster plot of action potentials recorded from all of the 16 electrodes during many IISs is shown, time-locked to the stimulus pulse. Action potentials are evoked by the stimulus at low latency following each pulse. The inset shows sample evoked AP waveforms recorded from one of the 16 electrodes during the experiment. This experiment is further characterized in Rolston et al. (2009a).