Figure 2.
Electrical stimulation utilizing MIMO predicted CA1 output patterns, facilitates DNMS performance. (A) Patterns of recorded CA3 cell firing in hippocampal array, shown as a heatmap (left), constitutes the input for online implementation of the MIMO model (center) to predict CA1 firing pattern (Figure 1C) indicated by red “tick” marks in hippocampal (CA1) layout (at right). This MIMO output pattern is fed to a programmable 8 channel stimulator (Supplemental Material) which delivers up to 3.0 s trains of bipolar electrical stimulation pulses (middle right) to the CA1 electrode locations showing the same firing pattern in each hemisphere. Stimulator output (photo display) is shown for 4 of the 8 channels to indicate different frequencies and intensities of stimulus trains delivered to separate CA1 locations (Supplemental Material). The time lag between CA3 recording, MIMO calculation and output of CA1 stimulation was approximately 50 ms. (B) DNMS performance graph of trained animals (n = 9) for delays of 1–60 s compares effects of 3.0 s stimulation delivered either: (1) at the time the SR occurred (Stim at SR) vs. No Stim [F(1, 731) = 11.50, p < 0.001], or (2) delayed for 3.0 s after the SR was made (Stim after SR) vs. No Stim [F(1, 731) = 3.17, n.s.] (see inset lower right). Asterisks (*p < 0.01, **p < 0.001) indicate significant difference in DNMS performance compared to control (No Stim.) trials (Berger et al., 2011). (C) Cumulative effects of MIMO generated SR stimulation over successive trials (Hampson et al., 2012a) shows progressive increase in overall mean (± s.e.m.) % correct performance in 30 trial blocks for animals (n = 5) receiving 25–30 SR stimulation trials (Stim Trials) per session for 15 sessions. Red curve (squares) shows overall performance on remaining trials within the same behavioral sessions in which no stimulation was delivered (No Stim). Inverted triangles (dotted line) shows performance over the same number of successive trials of equivalently trained animals (n = 20) that never received SR stimulation (Never Stim). Stim vs. Non-stim trials: F(1, 145) = 9.42, *p < 0.01,**p < 0.001, Stim. vs. Never Stim: F(1, 1349) = 15.72, p < 0.001, Non-stim vs. Never Stim. F(1, 1349) = 11.29, †p < 0.01, ‡p < 0.001.