50 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS OLFACTORY BULB ---.-------- GRANULAR CEL ! OLFAc TORY TRACT MITRAL CELL GLOMERULU5 OLFACTORY EPITHELIUM TO HIGHER BRAIN CENTERS RECEPTOR CELL Figure 2. Schematic illustrating the basic anatomical elements of the olfactory system plasma membranes. Resembling other cellular transduction systems, notably those of audition and vision, an important feature of the transduction events in chemoreceptors is that they are membrane phenomena (23). Delicate bundles of fine unmyelinated fibers, collectively called the olfactory nerve, pass from the receptor cells, enter at the olfactory bulb surface and terminate in the glomeruli level. The individuality of the olfactory information generated in a single receptor cell probably is retained up to the level of the glomeruli. A redistribution is believed to occur between the two levels of the glomeruli and the mitral cells, suggesting that the bulb processes the original in- formation before delivering it to the higher centers. At a deeper level within the bulb, the mitral and granule cell synapses are concerned both with olfactory processing and with integration of feedback information passing from the higher centers of the brain through the granule cells. It should be noted at this point that the human olfactory ca- pability generally rivals that of vision and audition. For example, in man there are circa 107 olfactory receptors, each of which can conduct up to ten impulses per second (24). Thus, the peak information capacity of the receptor membrane is approximately 108 bits per second, a figure quite close to the visual and hearing systems. 2.2 THE OLFACTORY CORTEX AND THE LIMBIC SYSTEM Whereas releaser pheromones exert their effect by rapid "recognition and association," primer pheromones somehow must affect the endocrine system. In this regard, let us examine the olfactory cortex, which is defined as the sites that receive direct synaptic outputs from mitral cells in the olfactory bulb. Despite overgrowth from the cerebral cortex, the phylogenetically primitive olfactory cortex mediates social and sexual be- havior of most mammalian species studied. Several areas of this primordial cortex receive direct projections from the mitral cells of the olfactory bulb via the lateral olfactory tract. The olfactory cortex serves as a powerful relay, since the outgoing in- formation channels are approximately 100 times more numerous than the incoming mitral fibers. The relationship between olfactory and limbic parts of the brain are simplistically di-

PHEROMONES (OLFACTORY COMMUNICATION) 51 OB Figure 3. Schematic relationship between olfactory and limbic systems (ref. 25). Olfactory Cortical Struc- tures (shaded circles), Limbic System (open circles), Olfactory Bulb (OB), Mitral Cell (M), Granular Cell (Gr), Glomerulus (Gl), Anterior Olfactory Nucleus (AON), Prepyriform Cortex (PP), Amygdala (AM), En- torhinal Cortex (ER), Olfactory Tubercle (OT), Septurn (SEP), Hypothalamus (HYP), Hippocampus (HIP), Lateral Olfactory Tract (LOT) picted in Figure 3 (25). These areas are interconnected in highly complex ways and only in the past few years has a number of new methods been acquired for studying them. Hence, it can be expected that a more sophisticated diagram will replace Figure 3 in the near future. It is fair to state that at this time a unanimity of opinion does not exist pertaining to the intricate relationships among the various parts of the olfactory and limbic systems. The limbic system is believed to be concerned with visceral and be- havioral mechanisms, particularly those associated with the expression of emotional states and with sensory and sexual functions. The anterior olfactory nucleus is thought to serve as part of a negative feedback loop that affects mitral cell output. Fibers from the olfactory tubercle (a rudimentary structure in man) passing to the septal area ap- pear to be principally non-olfactory. In fact, recent observations (26) suggest that the olfactory bulb has certain general modulatory functions in addition to its sensory role as a processor of olfactory information. One of the main inputs to the hippocampus comes from the entorhinal cortex, which in turn receives direct connections from the olfactory bulb. The hippocampus is well developed in such animals as the dolphin which lacks olfactory bulbs, but evidence indicates that the hippocampus receives inputs from the olfactory bulb, when present. The hippocampus may play a role in odor memory (27). Interestingly, olfactory memories are unique in that specific odors can be retained significantly longer than can visual or auditory memories (28). It is not uncommon for people to be vividly reminded of particular events, over long periods of time, which were associated with certain odors. The largest site in the olfactory cortex is the prepyriform cortex, or anterior pyriform cortex, generally regarded as the primary cortex in the olfactory pathway. Axons that leave this area distribute, inter alia, to the surrounding olfactory regions and parts of the hypothalamus. Consequently, the prepyriform cortex is strategically located to affect central brain structures that are cru- cially involved in many types of behavior. Recently it has been demonstrated that fibers project from the prepyriform cortex to the thalamus, one of the key relay centers of the brain to the frontal cortex (29). Such a thalamic connection to neocortex raises the possibility of greater sophistication and association with other stimulus events than