To reliably encode information about the environment, neurons must modify their activity profiles and even connectivity to accurately interpret complex stimuli. Cortical feedback projections to the olfactory bulb are uniquely positioned at the interface between detection-based processing that is driven by sensory input and analytical processing occurring in the piriform cortex. This arrangement makes these projections an ideal target to study how learning reshapes neuronal activity profiles. I have developed an approach that will allow for a comprehensive analysis of the axonal activity of principal neurons in the piriform cortex, while mice learn a task requiring them to identify a specific odor embedded in complex mixtures, thereby providing unique insight into olfactory scene analysis. My approach will also provide a detailed analysis of the connectivity between cortical axons and their postsynaptic targets in the olfactory bulb, which will reveal how the olfactory bulb integrates processed information from the piriform cortex. The outcomes of these studies will provide novel insight to how the brain to updates its stimulus-encoding scheme from a synthetic to analytical representation of a stimulus environment.
This work is ongoing and is the mentored phase of a National Institutes of Health Pathways to Independence Award. This project is co-mentored by Profs. Venkatesh Murthy and Naoshige Uchida at Harvard University.
Animals, including humans, interact with their chemical environment through specialized receptor cells found within the nasal epithelium. Upon odorant binding, these neurons transmit information to the olfactory bulb, the initial site of sensory processing in the olfactory system. However, our understanding of how these cells ultimately communicate information about odor identity and concentration to the brain is limited.
In this project we first developed a theoretical framework describing how blends of odor stimuli are detected and encoded by olfactory sensory neurons, with a focus on antagonistic interactions. A key prediction of the model is that antagonism in sensory neurons could normalize input to the olfactory bulb. I then tested the hypotheses generated by our model using in vivo calcium imaging to measure the stimulus-evoked activity in olfactory sensory neurons in live animals. This work revealed that olfactory sensory neurons are far from simple relays and that their nonlinear interactions fundamentally affect olfactory processing. Another component of this project investigated the role of ion channels downstream of odor receptor binding to how olfactory sensory neurons detect odors and transmit odor information to the brain.
This work was completed as a postdoctoral research fellow in the laboratory of Prof. Venkatesh Murthy at Harvard University. These studies resulted in the following publications:
Input to the olfactory system arises from sensory neurons within the epithelium of the nasal cavity. Sensory neurons project axons to specialized networks in the surface of the olfactory bulb called glomeruli that each receive input from a single sensory neuron subtype. While each subtype of sensory neuron has a preferred odorant ligand, they may also bind other ligands across a range of affinities. Therefore, in the presence of any odor, a few glomeruli will receive strong input from sensory neurons, while many others will receive weaker input, thereby potentially obscuring the brain's interpretation the odor environment of an animal.
A potential mechanism to overcome this limitation is through filtering of weak signals from “non-preferred” ligands. In this project, I tested whether the local network of neurons that surround glomeruli could perform this function. These cells, which include glutamatergic external tufted cells (eTCs) and GABAergic periglomerular (PG) cells, act together as a signal detection mechanism that selectively filters weak sensory inputs in favor of strong signals. Two of the primary goals of this project were to (i) test whether PG cells or eTCs are preferentially activated by differential levels of sensory input. This allows for low-level olfactory input to selectively activate inhibitory PG cells, thereby filtering weak sensory input signals. (ii) To determine if PG cell activity can be modulated by local glutamate released from eTCs, which may increase the effectiveness of weak signals and produce temporal patterning in glomerular activity.
This work was completed as my dissertation work in the laboratory of Prof. Nathan Schoppa at the University of Colorado School of Medicine. These studies resulted in the following publications: