Imaging mitral cell population activity in vivo in the mouse olfactory bulb

Odor inputs arriving in the olfactory bulb via axons of olfactory sensory neurons are transformed by bulbar circuits, and are conveyed to higher brain areas by mitral/tufted cell axons. This transformation, which involves several classes of interneurons, is not well understood. Recently, we have used real-time optical imaging in gene-targeted mice and a large set of odorants (~100), to shed light on the organization of odor inputs on the dorsal surface of the olfactory bulb (Nature Neurosci, 12:210). These studies have raised exciting questions about how odor inputs are transformed and represented at the level of mitral cells, which are the major output channels from the bulb. We have measured the activity of hundreds of mitral cells simultaneously using multiphoton microscopy in transgenic animals that express the genetically encoded indicator GCaMP2 in mitral cells. We compared the odor selectivity of mitral cells with that of glomerular inputs by using the same large panel of odorants used in our previous studies. We find that spatial patterns of population activity in mitral cell apical tufts are similar to the presynaptic maps constructed previously from OMP-synaptopHluorin mice. We were also able to record for the first time robust odor-evoked responses from a large population of individual mitral cell lateral dendrites, and find wide diversity in their responses. Intriguingly, the time courses of odor responses were significantly different in apical tufts and lateral dendrites. This may reflect different sources of calcium in the different compartments (synaptic vs. action potentials), and/or different patterns of electrical activity. Detailed characterization of the odor response maps and dynamics are underway. Measuring activity in different subcellular compartments of mitral cells - apical tufts, cell bodies and lateral dendrites - will reveal how odor representation is progressively transformed in freely breathing mice.