Inhibition controls levels of pattern separation in granule cells through different neural codes.

(A) Single GCs were recorded twice in response to the same input set (P10Hz, R = 0.76 at τw = 10 ms, shown in Fig 1B): First in normal aCSF, then under conditions of partial inhibitory block (aCSF + 100 nM gabazine, gzn), without changing any other parameter (i.e. same stimulation location and intensity). (B) Partial disinhibition of GCs led to higher FR and a higher propensity to fire small bursts of spikes riding on the same EPSP, as illustrated in A and evidenced by an increased p(Burst) (probability of firing more than one spike between two input pulses). FR and p(Burst) were computed for each recording set (n = 7 GCs). Paired t-test (FR and p(Burst) respectively): p = 0.02, p = 0.04. (C) Pattern separation graphs showing the pairwise output similarity as a function of the pairwise input similarity, as measured by R, NDP or SF at the 10 ms time scale (mean+/-SEM) across recordings in 7 GCs. Data points below the identity line (dashed) correspond to pattern separation. Partial block of inhibition in GCs led to a significant decrease in pattern separation through all similarity metrics (ANCOVA with separate-lines model fitting 70 data points per treatment group: p (D) Cumulative frequency distributions of the distance of (pairwise Sinput, pairwise Soutput) data points to the identity line in pattern separation graphs as in C (insets show medians). Positive values of the x-axis correspond to pattern separation, and negative values to pattern convergence. Red curves (after gzn) are all shifted to the left of their black counterparts (before gzn), showing a decrease in pattern separation at all time scales. The shift is more pronounced at larger time scales for R and NDP, at smaller time scales for SF. ANCOVA on (pw Sinput, pw Soutput) data points with separate-lines model: p w up to 1000 ms for R and NDP, p (E) Average levels of pattern separation via Compactness, Occupancy or FR codes were measured for each recording set (as in Fig 6B). Surprisingly, partial block of inhibition did not significantly change the variations in FR or binwise Compactness of output spike trains, but it led to less pattern convergence or even pattern separation through variations of Occupancy (paired t-test: p = 0.008, 0.024, 0.031 for τw = 10, 20 and 50 ms respectively, p > 0.05 for larger τw).