How Does the Brain Smell?

transmembrane domain receptors encoded by a family Sensory stimuli are detected by specialized receptors of more than a thousand genes (Buck and Axel, 1991). in sensory organs, and the signals hence generated flow Convergent lines of evidence strongly suggest that indithrough multiple and interconnectedcenters of the brain vidual olfactory sensory neurons express only 1 or few where they are analyzed and processed into complex of the 1000 receptor genes (Ressler et al., 1993; Vassar sensory perception. Processing of the sensory informaet al., 1993). In addition, it has been demonstrated in tion requires the coding of sensory inputs into specific rodents that all neurons expressing the same receptor patterns of neuronal activity. A common mechanism for (and therefore presumably responsive to a small subset sensory information coding is provided by the topoof odors), although randomly distributed in domains of graphic organization of sensory neurons and their axothe epithelium, project their axons to one or a small nal projections, such that sensory centers represent an number of discrete loci or glomeruli within the olfactory internal map of the external sensory world: the body bulb (Ressler et al., 1993, 1994; Vassar et al., 1993, 1994; surface, the visual world, the frequency of sounds. In Mombaerts et al., 1996). The positions of specific glothat manner, the quality of sensory stimuli is encoded meruli are topographically fixed, and are conserved in by the spatial coordinates of neuronal activity in high the brains of all animals within a species. These data sensory centers of the brain, and the discrimination beprovide physical evidence that the olfactory bulb defines tween sensory signals results from the stimulation of a two-dimensional map that identifies which of the topographically distinct subsets of neurons. numerous receptors have been activated within the senThe olfactory system is a molecular analyzer that can sory epithelium. This led to an attractive model of olfacdiscriminate a vast array of odorants with large variety tory coding in the brain, according to which discriminain chemical structure. How does the brain determine tion of odor quality would result from the detection by which odor has been detected by olfactory sensory neuthe brain of specific patterns of glomeruli activity. rons? Olfactory discrimination raises a peculiar problem Testing the Molecular Model by Directly Looking since odorant molecules per se do not convey any spaat Odor Signal Processing in the Brain tial information. Molecular approaches, however sophisticated, provide Vertebrate and insect olfactory systems display coma view of sensory processing that lacks functional permon organizational and functional characteristics. The spective. In this regard, a milestone has recently been initial event in odorant detection requires the specific reached with two independent studies performed in the interaction of odorant molecules with odorant receptors zebrafish, Danio rerio (Friedrich and Korsching, 1997) expressed on the cilia of olfactory neurons. The verteand in the honeybee, Apis mellifera (Joerges et al., 1997), brate olfactory epithelium (and the insect antenna) condescribing the optical imaging of glomerular activation tains several thousand bipolar olfactory sensory neuafter exposure of olfactory sensory neurons to various rons, each projecting to one of several glomeruli in the natural odorants. Ingenious tricks allowed the use of main olfactory bulb (the antennal lobes of insects). OlCa21 indicators to directly monitor glomerular electrical factory glomeruli are distinctive bundles of neuropil activities in a significant portion of the fish olfactory bulb found in the olfactory system. Their number varies in and the honeybee antennal lobes when various odorant different species: rodent olfactory bulbs contain several stimuli are presented to the distant olfactory sensory thousand glomeruli; fishes and insects have 10-fold organs. These two publications are of special interest fewer. Glomerular structures result from the converbecause they confirm the topographic organization of gence in the bulb (or the antennal lobes of insects) of the olfactory system revealed by molecular genetics in thousands of axon terminals that originate from olfacrodents and reinforce, but also go beyond, the model tory sensory neurons and that establish synapses with of olfactory discrimination predicted from molecular dendrites of mitral and tufted cells (output neurons in studies. insects) and of various classes of interneurons. Zebrafish olfactory sensory neurons were loaded with Discrimination between odors requires the specific a Ca1 indicator that distributes throughout the neuronal interaction between odorant molecules and odorant recell bodies and axon terminal, resulting in presynaptic ceptors and theprecise recognition by the brain of which labeling of the fish olfactory bulb, which was observed subset of receptors has been activated by a given odorin explant preparation of the system. Experiments with ant. Independent molecular and functional approaches honeybees were performed by incubating the entire inhave recently provided a model for the specific recognisect brain in Ca indicators, which results in both pretion of odors by the brain, which involves the translation and postsynaptic labeling. After odors were delivered of odorant quality into arrays of topographically segreto the freely moving antennae, the fluorescent changes