Stimulus novelty uncovers coding diversity in visual cortical circuits

Abstract

The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli. Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well as behavioral and task information. At the population level, the direction of these changes is consistent with engagement of the Vip-Sst disinhibitory circuit. At the single cell level, we identify separate clusters of Vip, Sst, and excitatory cells with unique patterns of novelty-induced coding changes. This study and the accompanying open-access dataset reveals the impact of novelty on sensory and behavioral representations in visual cortical circuits and establishes novelty as a key driver of cellular functional diversity.

Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex

“…This public dataset contains 2-photon calcium imaging from transgenic mice expressing the calcium indicator GCaMP6f in excitatory neurons (Slc17a7-IRES2-Cre;Camk2a-tTa;Ai93), Sst inhibitory neurons (Sst-IRES-Cre;Ai148), and Vip inhibitory neurons (Vip-IRES-Cre;Ai148). The data was collected with the Allen Brain Observatory experimental pipeline which uses standardized data collection and processing (Garrett et al 2023;de Vries et al 2020).…”

“…Running had no bearing on the task. These mice learned the task through a standardized training pipeline and were selected for imaging based on a consistent criteria of minimum task performance (Garrett et al 2023;Groblewski et al 2020).…”

“…The dataset contains imaging while mice performed the task with both familiar and novel stimuli. Novel stimuli have dramatic effects on neural activity (Garrett et al 2023), so we restricted our analysis to imaging during familiar image sessions. Our neural dataset contains 8,619 excitatory cells (21 imaging sessions, 9 mice), 470 Sst cells (15 imaging sessions, 6 mice), and 1,239 Vip cells (21 imaging sessions, 9 mice).…”

“…The Allen Institute Visual Behavior -2p calcium imaging dataset also contains neural activity in response to novel stimuli. Garrett et al 2023…”

“…Here we investigate how the Vip-Sst circuit in visual cortex mediates strategy dependent demands. We used the recently collected Allen Institute Visual Behavior -2p calcium imaging dataset to examine how the activity of Vip, Sst, and excitatory cells depend on strategy preferences during a change detection task (Garrett et al 2023;brain-map.org). This dataset, collected with the Allen Brain Observatory experimental pipeline, contains two-photon calcium imaging in genetically defined cell types collected while mice performed a visual change detection task.…”