Imaging odor coding and synaptic plasticity in the mammalian brain with a genetically-encoded probe.

We have used the genetically-encoded fluorescent exocytosis indicator synaptopHluorin (spH), expressed selectively in mouse olfactory receptor neurons, to image odor representations at the input to the olfactory bulb. The olfactory bulb is a powerful system for in vivo fluorescence imaging because its inputs are segregated into receptor-specific functional units (glomeruli) that are optically accessible and receive massively convergent input from sensory neurons. In a line of transgenic mice expressing spH under the control of a receptor neuron-specific promoter (OMP), odorant-evoked patterns of receptor neuron input to approximately 10% of the olfactory bulb can be imaged with excellent spatial resolution and sensitivity during single brief odorant presentations. Odor representations are similar across mice and can be imaged repeatedly in the same animal for months. In olfactory bulb slices from OP-spH mice, shock-evoked spH signals are rapid and linear reporters of transmitter release, although control for changes in extracellular pH is critical for proper interpretation of the spH signals. These features have allowed us to characterize the functional organization and mechanisms of presynaptic modulation of transmitter release at the first olfactory synapse. The capacity for long-term chronic imaging permits the direct visualization of the function regeneration and remapping of input to the olfactory bulb after lesions of the nasal epithelium.