The visual scene is constantly changing, and the detection of novel stimuli among familiar ones can be crucial for survival. One strategy is to continuously adapt the sensitivity of sensory neurons to suppress responses to common stimulus features while enhancing responses to new ones.  We have recently demonstrated that fast contrast adaptation of pyramidal cell (PC) responses in V1 does not simply involve a reduction in gain over seconds (depression): as many neurons increase in gain (sensitization) reflecting their control by distinct inhibitory microcircuits1.  PC and interneuron responses also adapt over longer time-scales, for instance when the animal habituates to a neutral stimulus repeated over days2. We have investigated whether the local inhibitory circuits that generate fast contrast adaptation are also involved in habituation.
To answer this question, we presented mice with a 10 s visual stimulus repeatedly during 6 sessions while monitoring GCaMP6f activity. To causally test for interneuron connectivity, we expressed the inhibitory opsin ArchT. During the stimulus, we measured changes in response amplitude (ΔF/F) and adaptive properties expressed as an adaptive index (AI) positive for depressors and negative for sensitizers1. Experimental mice were humanely treated, and isoflurane was used as surgical anaesthesia according to UK legislation.
We found that PCs decrease their activity (ΔF/F: Session 1 [S1] 0.17 ± 0.006, n = 1195 cells; Session 6 [S6] 0.09 ± 0.005, n = 935 cells; p < 0.001 Mann-Whitney U test) and shift from depression to sensitization upon habituation to the stimulus (AI: S1 0.12 ± 0.009; S6 -0.11 ± 0.011; p <0.001 Mann-Whitney U test). Somatostatin interneurons (SSTs) increased their activity (ΔF/F: S1 0.40 ± 0.05, n = 51 cells; S6 0.67 ± 0.09 n = 94 cells; p < 0.01 T-test) undergoing a shift to sensitization (AI: S1 0.23 ± 0.04; S6 -0.26 ± 0.04; p < 0.001 T-test). Conversely, parvalbumin (PVs) interneurons dramatically decreased their activity (ΔF/F: S1 0.25 ± 0.02, n = 226 cells; S5 0.10 ± 0.01 n = 73 cells; p < 0.001 Mann-Whitney U test) as did VIPs (ΔF/F: S1 0.19 ± 0.03, n = 94 cells; S6 0.07 ± 0.02 n = 12 cells; p < 0.05 T- test). Optogenetically silencing SSTs we did not observe differences in PC inhibition when the stimulus was novel vs familiar (Delta Amplitude with Optogenetics: S1 0.13 ± 0.005, n = 993 cells; S6 0.13 ± 0.007 n = 690 cells; p = 0.605 Mann-Whitney U test). Conversely, silencing VIPs and monitoring SST activity revealed that SST adaptive properties are linked to VIP inhibition which is stronger when the stimulus is novel (Delta AI: S1 -0.40 ± 0.06, n=51 cells; S6 -0.24 ± 0.05 n = 94 cells; p PV->PC and VIP->SST ->PC.