VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination.

In the olfactory bulb (OB), olfactory information represented by mitral/tufted cells (M/Ts) is extensively modulated by local inhibitory interneurons before being transmitted to the olfactory cortex. While the crucial roles of cortical vasoactive-intestinal-peptide-expressing (VIP) interneurons have been extensively studied, their precise function in the OB remains elusive. Here, we identify the synaptic connectivity of VIP interneurons onto mitral cells (MCs) and demonstrate their important role in olfactory behaviors. Optogenetic activation of VIP interneurons reduced both spontaneous and odor-evoked activity of M/Ts in awake mice. Whole-cell recordings revealed that VIP interneurons decrease MC firing through direct inhibitory synaptic connections with MCs. Furthermore, inactivation of VIP interneurons leads to increased MC firing and impaired olfactory detection and odor discrimination. Therefore, our results demonstrate that VIP interneurons control OB output and play critical roles in odor processing and olfactory behaviors.