Online Lecture by Katie Ferguson

VIP interneuron contributions to state-dependent sensory processing

Visual information from the environment is rapidly and dynamically processed by a complex network of cortical neurons. Cortical activity patterns reflect not only changing sensory inputs, but also behavioral state (e.g., quiet wakefulness vs. active locomotion). Several lines of evidence suggest that inhibitory GABAergic interneurons (INs) may be key regulators of flexible cortical function. However, cortical GABAergic INs comprise several reciprocally connected, highly diverse subpopulations that are differentially activated during distinct states.

GABAergic INs expressing vasoactive intestinal peptide (VIP-INs) are strongly activated by neuromodulatory afferents during distinct behavioral states, and are thus uniquely situated to be key contributors to flexible cortical function. These cells predominantly inhibit somatostatin-expressing interneurons (SST-INs), but until recently methodological limitations prevented the study of IN-IN interactions in vivo. The relative impact of these highly non-linear cortical interactions may vary with behavioral or environmental context, and thus VIP-SST interactions may have a complex and largely unexplored role in the regulation of cortical activity.

We use two-photon calcium imaging in awake behaving mice to identify cell type-specific GABAergic IN contributions to sensory processing, to determine how behavioral state modulates the impact of GABAergic inhibition, and to identify how distinct GABAergic IN populations affect perceptual learning in a visual detection task. Our results uncover underlying state-dependent excitation of SST-INs and suggest a complex role for VIP-INs in regulating large-scale changes to sensory processing across behavioral states.