El-Boustani et al. reply

replying to S.-H. Lee, A. C. Kwan & Y. Dan Nature508,http://dx.doi.org/10.1038/nature13128(2014) Several recent studies have examined the function of parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) inhibitory neurons in V1 (refs 1, 2, 3). Although it is commonly agreed that these cell types alter the responses of pyramidal neurons in distinct ways—via divisive or subtractive inhibition—their specific roles remain a matter of debate. The Comment by Lee et al.4 presents new data suggesting that the differences between the results of Lee et al.2 compared to Atallah et al.3 and Wilson et al.1 could be explained by the strength and duration of laser stimulation used to optogenetically activate these two classes of inhibitory neuron. The data presented by Lee et al.4 now clarify that PV+ neurons, when probed with small amounts of optogenetic activation, do not significantly change the tuning of their target cells, confirming Atallah et al.3 and Wilson et al.1. The new SST+ results presented in the Comment4 show that SST+ neurons can subtract responses, consistent with Wilson et al.1, but we suggest that the switch of function of SST+ neurons in their data between short (1 s) and long (4–5 s) stimulation reveals a core principle of inhibition in cortical networks rather than simply being a peculiarity of stimulation protocols. The fundamental difference between these two conditions resides in the temporal overlap between inhibitory neuron activation and target-cell responses: when these overlap, inhibition is divisive (causing no change in tuning width of target neurons), but when they do not overlap, inhibition is subtractive (and reduces tuning width).