1 Olfaction: new frontiers for cognitive sciences. Franco Orsucci Cognitive Science Department, Rome International University General remarks. The perception of odours in humans is often viewed as an aesthetic sense, a sense capable of evoking emotion and memory, leading to measured thoughts and behavior. Smell, however, is also a primal sense, and it can elicit innate and stereotyped behaviors likely to result from the non- conscious perception of odours. It is evolutionarily the most primitive of the senses and for most organisms is the central sensory modality allowing communication with the environment. Whether smell is primal or aesthetic, whether it is conscious or non-conscious, organisms must have evolved a sensory system that recognizes olfactory information in the environment and transmits these signals to the brain, where they are processed to provide an internal representation of the external world. In mammals olfactory sensory perception is mediated by two anatomically and functionally distinct organs: the main olfactory epithelium (MOE) and the vomero-nasal organ (VNO). The main olfactory system recognizes most odors and ultimately sends fibres to higher sensory centers in the cortex, resulting in the conscious perception of odors and measured thoughts and behaviors. The vomeronasal system, however, detects pheromones and transmits this olfactory information via a separate pathway of neuronal projections to the emotive brain, the amygdala and hypothalamus. Thus, the VNO pathway bypasses higher cognitive centers, resulting in innate and stereotyped behavioral and neuroendocrine responses. How are the diversity and specificity of olfactory perception accomplished? The initial step in the discrimination of odors involves the interaction of odor molecules with receptors on the dendrites of sensory neurons. A few years ago, a laboratory isolated two large families of genes likely to encode the odorant receptors. These genes provide insight into how the information of odor binding in the periphery in the nose is processed centrally in the brain, to permit the discrimination of odors. One gene family encodes the receptors expressed in the MOE; in mammals it may consist of as many as 1,000 genes. Each gene directs the synthesis of a distinct receptor protein that traverses the membrane seven times. An independently evolved family of about 100 genes is likely to encode the mammalian pheromone receptors. The identification of two extremely large repertoires of odorant receptor genes provides a mechanism for the recognition of the diverse array of odors. Discrimination among odors, however, requires that the brain determine which of the numerous receptors a given olfactory stimulus activates. Individual olfactory neurons express only one of the 1,000 receptor genes, such that neurons are functionally distinct. The problem of determining which receptors have been activated by an odorant can therefore be reduced to a problem of distinguishing which neurons have been activated. As in other sensory systems, spatial patterns of olfactory sensory neurons, or their projections, may provide a topographic map of receptor activation that defines the quality of a sensory stimulus. There are a number of possible scenarios for arranging neurons and their axons in the nose and brain. In one model, neurons that bear a given type of receptor would be localized in the olfactory epithelium. Activation of neurons at specific sites would then define the quality of an odor. Alternatively, neurons carrying one type of receptor could be randomly positioned in the epithelium, but their axons would converge on discrete areas in the brain. In this case, exposure to a particular odor would result in defined patterns of activity in the brain.