Fig. 2: Ultrafast optogenetic inhibition in freely moving animals.

A Injection, stimulation, and recordings in M1. B Activity of sorted units without (left) and with (middle) PVR management. The PVR management algorithm first subtracts an estimate of the PVR and then estimates in which trials the subtraction was incomplete. This remaining PVR trial percentage (green) is then used to weight the average across trials for each time point (lower left and right panel). The data shown are from animals 540, 548, and 549. C Relationship between opsin expression (red) and inhibition strength. To quantify the overall extracellular response, spikes were detected at a threshold of −30 µV on a per-channel basis without PVR management (PVR removed for visibility). GFAP immunostaining (green) was used to identify the BE probe location. Scale bar: 500 µm. D Single-trial extracellular traces for 40 inhibitions from one electrode channel (upper panel). Histogram of spikes detected with a threshold of −30 µV (lower panel). E Latency at different percentages of the pre-inhibition spike rate bootstrapped across all sorted units. n = 212 sorted units over two animals. Boxplots: central mark indicates the median, bottom and top edges refer to the 25th and 75th percentiles of the bootstrapped data. F Illustration showing that the spike inhibition latency can be shorter than the time constant of the hyperpolarizing function. G Percentage of pre-inhibition spike rate as a function of the total light power that exits the side-emitting fiber. n = 45, 45, 51, 63, and 63 sorted units with non-NaN-bins during stimulation for each light intensity, respectively. For a description of the Box-plot see panel E. H Comparison of inhibition in vivo for the BE probe (top) and the fiber matrix (bottom). Spikes were detected at a threshold of −30 µV on a per-channel basis without PVR management. I Inferring neuronal activity after inhibition onset from pre-inhibition activity. The units were divided into three groups corresponding to low (left, p = 0.98), moderate (middle, p = 0.0035), and high (right, p = 0.0249) average firing rates. *p < 0.05, **p < 0.01. Two-sided t-test. No adjustments for multiple comparisons. Source data are provided as a Source Data file.