Figure 6.

Integration of Multi-input, multi-output (MIMO) nonlinear model (a) to calculate SR encoding via spatiotemporal firing relations between hippocampal CA3 and CA1 recordings (b), to predict CA1 firing (c) from CA3 recordings (d), and generate patterned stimulation (e) for feedback to Layer CA1. The anatomical diagrams at the left show placement of CA3 and CA1 multi-cell recording tetrodes into the associated transverse fields along the longitudinal axis of hippocampus. The recordings on correct DMS trials from these spatially distinct and layer specific tetrodes were fed into the MIMO model with CA3 as the input (blue arrow) and CA1 as the output pattern (red arrow). The MIMO model predicted correct CA1 output (i.e. “Strong Codes”) from CA3 input computed over the Sample Phase (shaded rectangles) based on fine temporal relationships between spike trains recorded on correct trials at different spatial locations within hippocampus. On stimulation trials, trains of electrical pulses mimicking the predicted Strong Code output spike trains were delivered to the same CA1 hippocampal electrode locations the patterns were recorded from. MIMO model controlled stimulation patterns applied to the respective CA1 recording locations consisted of multi-channel biphasic pulses of 10–50 μA, 1.0 ms duration with a minimum 50 ms between stimulation pulses, with no more than 20 stimulation pulses per second per channel.