Abstract
In mammals, odorants are detected by a large family of receptors that are each expressed in just a small subset of olfactory sensory neurons (OSNs). Here we describe a strain of transgenic mice engineered to express an octanal receptor in almost all OSNs. Remarkably, octanal triggered a striking and involuntary phenotype in these animals, with passive exposure regularly inducing seizures. Octanal exposure invariably resulted in widespread activation of OSNs but interestingly seizures only occurred in 30–40% of trials. We hypothesized that this reflects the need for the olfactory system to filter strong but slowly-changing backgrounds from salient signals. Therefore we used an olfactometer to control octanal delivery and demonstrated suppression of responses whenever this odorant is delivered slowly. By contrast, rapid exposure of the mice to octanal induced seizure in every trial. Our results expose new details of olfactory processing and provide a robust and non-invasive platform for studying epilepsy.
Highlights
Our senses evolved to provide useful information about the environment
M72-IRES-LacZ was expressed in about 5% of olfactory sensory neurons (OSNs), we observed very few lacZ positive fibers in the main olfactory bulb (MOB) (Fig. 1C, E)
In all cases, essentially the entire population of OSNs expressed high levels of c-fos. These results suggest that the variation in symptoms that we observed is more dependent on differences in signal processing in the MOB and higher brain centers than the overall extent of main olfactory epithelium (MOE)-activation
Summary
Our senses evolved to provide useful information about the environment. stimuli received outside their normal context often elicit undesirable effects: e.g. a bright flash of light temporarily blinds an individual adapted to dim conditions. Olfaction detects and distinguishes odorants through changes in activity of olfactory sensory neurons (OSNs) and provides mammals with exquisite ability to separate novel chemical signatures from a more constant but sometimes intense background. Mammalian olfaction is initiated by activation of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE) through detection of odorants by a large family of odorant receptors (ORs) [1,2]. Each OSN expresses a single OR [3,4] and neurons expressing the same OR project to stereotypic sites in the main olfactory bulb (MOB) forming structures known as glomeruli [5,6,7,8]. Axons of the M/T cells associated with a single glomerulus project to a distributed array of pyramidal cells in the piriform cortex. It has been suggested that an extensive recurrent excitatory network within the piriform cortex amplifies responses and results in the widespread representation of even minor olfactory stimulation [16,17]
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