The senses start with the sensory organs. In the olfactory system, odors are detected by the olfactory sensory neurons (OSNs) in the nose. The OSNs project to the olfactory bulb, which relays information deeper into the brain. The OSNs respond to a subset of odors via the olfactory receptors they express on the tip of the ciliated dendrites. Each neuron expresses only a single type of olfactory receptor; this limit the repertoire of odorants it can respond to. On the other hand, each odorant can active a subpopulation of OSNs. Different odorants activate different subpopulations. Therefore, there is a unique combination of OSNs expressing different ORs to encode an odor stimulus. This forms a “combinatorial” odor code.
The combinatorial odor code can be visualized in the olfactory bulb because neurons expressing the same receptor project their axons into two places in each olfactory bulb, into structures call the glomeruli. Each glomerulus corresponds to a single type of olfactory receptor. The patterns of activity of the glomeruli therefore reflect the patterns of activation of the unique OSN ensembles. One fundamental question in olfaction is how does the glomerular activity encode odor information? And what is the neural computation in the bulb that generates the dynamic and spatial patterns that allows the animal to recognize odorants.
To answer these questions, we have generated transgenic mice that express the calcium sensor G-CaMP2. With an olfactometer custom-built in the lab, we can precisely control the imaged odor-evoked responses from live animals. We perform systems level examination of glomerular response to large dimensional odor stimuli. These analyses reveal the organization principle of glomeruli.
The mitral cells relay information transmitted from the glomeruli to the cortices. They are part of a network of interconnected neurons in the bulb. To investigate how the mitral cells respond to odors, we use multi-electrode arrays to record odor-evoked changes in the spiking patterns of the mitral cells. By comparing the response patterns between the glomeruli and the mitral cells, we ask how the odor code is transformed by the neural network in the bulb. Furthermore, we are adopting a transgenic approach using molecular tools such as channelrhodopsin and halorhodopsin to investigate the network interactions in the bulb.
There are two major groups of interneurons in the olfactory bulb. The periglomerular cells mediate inhibition and excitation among the glomeruli and the granule cells mediate inhibition among the mitral cells. Collectively, these neurons shape the response of the glomeruli and the mitral cells. With electrophysiological and optical approaches, we are interested in understanding the role of the interneurons in transforming the odor-evoked responses.
Stowers Institute | NIH | NIDCD | Kansas City