When searching for resources such as food animals accumulate information over time. How this is accomplished by the olfactory system is largely unknown due to two constraints. First, the sensory cues used for odor-guided searches (odor plumes) are notoriously complex and unable to be completely predicted by computational models. Second, the current technology for detecting odor plumes is too large to use with freely moving animals. These limitations mean that our understanding of how animals search with odors, an ability seen across numerous diverse species, is still in its infancy. This is especially true for mice, animals that are one of the major biomedical model species and that rely on odors to find food. This proposal will use new head-mounted odor sensors to accurately detect odor plume encounters by mice while they are using these sensory cues to search. We will combine these sensors with Neuropixels probes to record from hundreds of neurons simultaneously and chart the flow of information through the olfactory system and to cortical decision- making structures. Specifically, we will test the relationship between neural signatures of odor encounters in the olfactory cortex and the guidance of search behavior by the orbitofrontal cortex. We will assess how information is transmitted between these two connected structures as well as how the orbitofrontal cortex accumulates odor evidence. These goals will be accomplished by training mice to find the source of a volatile organic compound, ethanol, which will be detected by miniature sensors that we have altered to become fast response and head-mountable. While animals search for the source of this odor, the sensor will transmit any contact that they make with the odor plume. We will then reconstruct the information obtained by the animal during its search to ascertain how this information guides decisions. Using Neuropixels probes we will extend this analysis into the large-scale neural circuits that support this complex behavior. By recording neural activity simultaneously in the olfactory and orbitofrontal cortices we will test how odor information is routed from sensory to decision-making areas under multiple odor-guided search conditions. These conditions will include searches in complex environments with background odors. We will functionally test this circuit by targeted optogenetic inactivation of the feedback pathway from the oribitofrontal cortex to the olfactory cortex. We will measure the impact of this inactivation both behaviorally and neurophysiologically and quantify changes in odor information in both structures. We postulate that orbitofrontal cortex will accumulate information during odor-guided search and that feedback from the orbitofrontal to the olfactory cortex will suppress background odor input, enhancing search effectiveness. The successful development of this paradigm can serve as an innovative new model for studying the interactions between sensory and decision-making systems of the brain, enhancing understanding of how the brain accumulates information from complex sensory signals.
We will be studying the mechanisms through which the brain integrates and processes complex and dynamic sensory information to guide natural behaviors. These studies will have applicability to psychiatric disorders that involve deficits in sensory integration, such as schizophrenia and autism spectrum disorders and will provide insight into the cognitive deficits seen in pathological conditions such as Alzheimer?s disease and Parkinson?s disease.
