The sense of smell plays critical roles in mediating a variety of behaviors in animals including humans. Odor molecules activate olfactory sensory neurons (OSNs) in the nose, which carry the information to the olfactory bulb (OB) and subsequently to the olfactory cortical regions including the piriform cortex and anterior olfactory nucleus/tenia tecta (AON for simplicity). The connectivity of olfactory cortices to their downstream targets is presumably important for olfactory-guided behaviors, but little is known about anatomical connections and functional properties of these downstream targets. One such structure is the nucleus of lateral olfactory tract (NLOT), which connects reciprocally with some cortical and limbic areas and is implicated in olfactory-guided behaviors. We recently discovered that the NLOT is a major downstream target of the AON via anatomical tracing in a novel mouse line, which allows genetic access to AON neurons. In addition, we verified functional connectivity of this pathway since AON neurons make excitatory monosynaptic connections onto NLOT neurons. Further, ablation of glutamatergic NLOT neurons led to severe deficits in olfactory guided behaviors. The preliminary studies lead to the hypothesis that the NLOT is an essential neuroanatomical structure in an olfactory circuit that is critical for odor-guided behaviors. Multidisciplinary approaches (circuit tracing, in vitro electrophysiology, pharmacology, optogenetics, chemogenetics, in vivo fiber photometry, and behavior) will be used to pursue three specific aims. We will (1) delineate anatomical and functional inputs to NLOT neurons, (2) determine in vivo activity of NLOT neurons during olfactory-guided behaviors, and (3) determine loss-of- function effects of NLOT neurons on olfactory-guided behaviors. Overall, the current study will provide critical insights into the NLOT neural circuitry and its role in olfactory-guided behaviors.
Smell dysfunction has a negative impact on quality of life and may be a sign of more serious health conditions including neurodegenerative and neuropsychiatric diseases (e.g., Alzheimer's, Parkinson's, and Schizophrenia). A better understanding of the neural circuits underlying olfactory-guided behaviors may help to develop new interventions for olfaction-related diseases.
