Project Summary Sensory perception, being aware of a stimulus, varies depending on brain state. During sleep, individuals fail to perceive many of the sensory stimuli that they would during wakefulness, a process referred to as state- dependent sensory gating. Most sensory modalities rely on the thalamus to act as a sensory gate during sleep; however, olfactory information can reach the cortex without the relay of the thalamus making it unclear how the olfactory system achieves sensory gating. Odor perception begins with the binding of odorants to the olfactory sensory neurons (OSNs) in the nose, which then project to the olfactory bulb (OB). From the OB, olfactory information is transmitted to the olfactory cortices (including the piriform cortex, PC) then to the orbitofrontal cortex (OFC). In this proposal, we will use optogenetics, electrophysiology, and natural odor stimulation in freely behaving mice to understand how the rodent olfactory system is able to gate sensory information. Preliminary studies suggest that olfactory information can reach the cortex without attenuation during sleep, as measured by larger evoked local field potential (LFP) amplitudes during sleep. Additionally, there is an increase in gamma oscillations following stimulation during wake but not sleep. We hypothesize that sensory responses (except for gamma oscillations) are largely preserved in olfactory cortices during sleep due to reduced top-down cortical inputs to the OB, which primarily function to decrease OB outputs by enhancing local inhibition. We will test this hypothesis in two aims. In Aim 1, during natural sleep and wake states, LFPs will be recorded simultaneously from multiple olfactory regions and single-unit recordings will be performed in the anterior PC in response to both an optogenetic stimulation and a natural odor stimulation that is delivered into the nasal cavity as to avoid the confounds of changed breathing in different brain states. In Aim 2, to further understand the role of the OB local inhibition in this process, instead of activating multiple OSN types (ie multiple glomeruli) by optogenetic stimulation, a single glomerulus will be stimulated to minimize the effect of lateral inhibition. Additionally, recordings will be performed under anesthesia to reconcile this result with previous studies on this topic. Together, these experiments will reveal the differences in olfactory information processing in natural sleep/wake states and provide a mechanism for these differences.