VNO Function - Pheromone Communication: The Vomeronasal Organ or VNO is the receptor organ of a sensory system involved in chemical communication. Among mammals, sex pheromones that advertise sexual readiness to potential mates are often, although not exclusively, detected by the VNO. Odors that are produced by one individual and detected by another of the same species are called "pheromones" if the process is a real communication with benefit to both sender and receiver. Sexual communication is only one example. Other communications could include information on territorial or aggression signals. The detection of non-pheromones by the VNO is well established for snakes (see "Snake Vomeronasal Organ"- with Figure 3, and Extended-text) and is theoretically possible in other species. Genetic studies indicate that vomeronasal sensory neurons use different types of receptor proteins to bind and detect chemicals than are used by the main olfactory system. Electrophysiological studies suggest that these receptor proteins are highly specific in their sensitivity to pheromone chemicals. Whether humans have functional VNOs is a matter currently under investigation (see "Human Vomeronasal Organ"- with Figure 2, and Extended-text).
Access of stimulus molecules: The narrow VNO duct (black dot at left end of VNO in the mammalian VNO diagram), opens onto the "floor" of the nasal cavity just inside the nostril in hamsters and mice. It is the only access for stimulus chemicals. These are thought to enter the nostril and dissolve in nasal mucus when the moist nose contacts sources of chemicals. For example, male hamsters and mice sniff and contact the genital area of females during courtship/mating behavior. The constriction of large blood vessels enclosed within the VNO capsule can act as a pump to draw stimulus-containing mucus into the VNO lumen. The vasomotor autonomic nerves controlling the pump enter the VNO capsule at its posterior end (in the dark shadows to the right of the VNO in the diagram). A similar pump seems to exist in most mammals. In some species, from cattle to cats, the VNO duct opens into the nasopalatine (NP) canal. This canal connects the nose with the mouth so stimuli might also enter the VNO after the animal licks a stimulus-source. In hamsters and other rodents the NP canal opens into the nose about halfway along the length of the VNO (under the arrowhead in the diagram) and is not likely to be a route for VNO stimulation.
Stimulus molecules: In many cases, VNO communication involves the detection of large non-volatile molecules, and contact appears necessary for stimulation. In hamsters, a protein, Aphrodisin, probably coupled with a small lipid molecule, may be the effective female pheromone. However, other substances, including volatile stimuli (odors) can stimulate VNO sensory neurons if delivered to them (See VNO Sensitivity and Extended-text for further details). In mice, VNO sensory neurons respond with nerve impulses to urine, which these animals deposit for communication. A number of chemicals identified as behaviorally-active components of mouse urine are capable of stimulating some VNO sensory neurons in tests in vitro.
VNO Sensitivity: VNO sensory neuron sensitivity to identified pheromone chemicals has not been extensively tested. However, recent publications indicate that mouse vomeronasal neurons can be exquisitely sensitive to low concentrations of chemicals proposed as pheromones in this species. These neurons do not respond to closely-related chemicals or other substances even at high concentrations. The accessory olfactory bulb (AOB) is the brain region that receives information from the vomeronasal organ. In mice, different AOB neurons respond very selectively when the animal investigates males versus females, or mice of different breeds, also suggesting a high selectivity of the system to socially relevant chemosensory signals. This kind of special sensitivity and selectivity are also features of pheromone sensory neurons in insects. It is different from the looser specificity of main olfactory sensory neurons. For the main olfactory system, a particular chemical is characterized by the combination of the several types of sensory neurons that respond to it. Each sensory neuron in the main system also responds to a range of other chemicals. (See Molecular Receptors, Specialist versus Generalist Functions or Extended-text).
Molecular receptors: Chemosensory neurons respond to low concentrations of chemicals because the chemicals "bind" to receptor-protein molecules on the neurons' surface. The tightness and selectivity of the binding depends on the "fit" between stimulus chemical and receptor protein. Effective binding triggers a cascade of processes inside the sensory neuron, generating nerve impulses. These nerve impulses carry the message back to the brain. There are two different super-families of vomeronasal receptor (VR) genes in rodents, potentially coding for about 200 different receptor proteins. If these proteins were all highly specific in their binding, about 200 chemicals could be detected and identified. In the main olfactory system there are about 1000 genes coding for olfactory receptor (OR) proteins (in rodents). These could potentially detect and discriminate millions of odor chemicals because the lower specificity allows different chemicals to activate different combinations of the same set of receptors (see Generalist versus Specialist Receptors). In both main olfactory and vomeronasal systems, each sensory neuron probably "expresses" (turns-on) only one VR or OR gene. All the many receptor proteins on that neuron's surface would then be of one type. Genetic analysis in humans shows that almost all the VR genes (and over half of the OR genes) that appear to be functional in rodents have mutated into non-functional forms (pseudogenes) over the course of evolution. The accumulation of mutations is a normal process in genes that are not essential for survival. Evidence from non-rodent species suggests that they may have different sets of functional VR genes. In the limit, some species may have no functional VR genes in common with the intensively studied rodent species. Because some of these species appear to have a functional VNO, there may be other gene families of vomeronasal receptors yet to be discovered. Whether any of these hypothetical genes might also be found in humans is entirely speculative. Cellular mechanisms that generate electrical impulses to carry sensory information to the brain also differ between vomeronasal and olfactory neurons. Deletion of essential genes for these mechanisms by genetic engineering in mice, result in abnormal social behavior. see Extended text).
Specialist versus Generalist Functions: The vomeronasal system may function as a specialist chemical detector system, where it is important to identify the chemicals. In such a system, the identity of the chemicals (or the identities and relative concentrations of a blend of chemicals) would carry pre-specified meaning. The sensory system of the receiving individuals would be expected to co-evolve with the capacity on the part of the "sending" individuals to produce specific chemicals. In a generalist system, like the main olfactory system, the identities of the chemicals may be unimportant so long as particular chemicals or mixtures can be discriminated from other chemicals or mixtures. Association of certain patterns of sensory input with particular circumstances or entities (presence of food sources, of predators, etc.) may be sufficient for adaptive behavior. Such an associational system works well with many different broadly-selective sensory neurons. Any two odors could be discriminated on the basis of relative similarities and differences in activity across many neurons of different specificity, but with no simple mechanism for identification. The ability of the main olfactory system to respond to newly synthesized molecules and the difficulty humans have in identifying odors except by their similarity to the odors of known objects are both consistent with this view.
Information pathway to the brain: The VNO sensory neurons have axons that leave the VNO capsule in bundles and extend dorsally across the nasal septum (red lines with yellow border) passing beneath the olfactory mucosa. The VNO axons carry these electrical signals to the accessory olfactory bulb (AOB - see diagram and Fig. 4). The AOBs process VNO input and lie dorsal and usually medial to the main olfactory bulbs, which process main olfactory (smell) input. The main olfactory bulbs (MOBs) receive their information from bundles of olfactory axons (thin blue lines) which come from olfactory sensory neurons in the olfactory mucosa within the nasal cavity. The VNO information from the AOB and the olfactory information from the MOB are carried by separate sets of "second-order" axons to the amygdala (red/yellow and thicker blue lines respectively). From there the VNO system projects directly to the preoptic area and to the hypothalamus; areas known to be involved in reproductive behavior (red/yellow lines). Further projections from the main olfactory system include the hippocampus, thalamus and cortex (blue lines). The VNO recipient areas of the amygdala and the preoptic area are active during VNO initiated mating behavior in rodents, and when males investigate female chemosignals. Initial evidence suggests the amygdala analyzes chemosensory input according to different criteria than the AOB. See Fig 4 and Extended-text).
Behavioral consequences of VNO Removal: After surgical removal of the VNOs under anesthesia and following full recovery, there is a serious impairment in mating behavior in sexually inexperienced (but not sexually experienced) male hamsters and mice. VNO removal in female mice and voles leads to a number of changes in reproductive behavior and physiology, including: failure of male stimuli to accelerate puberty in immature females, failure of adult group-housed females to influence each other's estrus cycles and failure of "foreign-strain" males to cause pregnancy block in recently impregnated females. In all these examples of sensory/hormonal interactions, the sensory component appears to be vomeronasal input (See Extended-text). Because VNO removal also damages the Nervus terminalis (NT), there is a slight possibility that some deficits attributed to loss of VNO function are due to loss of NT function. Experiments where the vomeronasal system was removed or damaged in new-born rabbits and in sheep show that the vomeronasal system is not involved in all pheromone communication. See Extended text.
Nervus terminalis: The Nervus terminalis (NT) or terminal nerve, is a complex of neurons and nerve fibers that extends from the nasal cavity to the brain along the course of the vomeronasal nerves. It by-passes the AOB and enters the forebrain behind the olfactory bulbs. Its nasal components are damaged when the VNO is removed so it is possible that some deficits in function attributed to VNO removal might be due to NT removal. However, specific damage to the NT without vomeronasal-system damage produces only slight deficits in mating behavior. Hormonal response to pheromones is not impaired. The NT is of interest in its own right even though its function is not clear. It follows the route by which the precursors of all forebrain GnRH (LHRH) neurons migrate into the brain during embryonic development, and remains in adults as an additional neural connection from nose to brain that is rich in GnRH containing cells and fibers. In some fish, especially elasmobranchs (sharks and rays) the NT ganglion contains the highest concentration of GnRH in the entire brain and in those species it may be the source of LH releasing actions on the pituitary (See description of "Terminal Nerve" in Encyclopedia of Neuroscience). The Nervus terminalis is present in all vertebrates whether or not they have a VNO and it has been suggested that the nerve fibers apparently innervating the human VNO are in fact NT fibers (See Human Vomeronasal Organ, Fig 2, and Extended-text).
Human VNO Function: Figure 2.
Humans have a VNO structure but recent studies have failed to find the types
of sensory neurons characteristic of VNOs in other species. One group of researchers
report that an electrical response can be recorded from the VNO pit in awake
humans in response to chemicals found in human skin. The researchers suggest
that the effective substances (steroids) are human pheromones but have not investigated
this possibility scientifically. The best documented examples of chemical (pheromonal?)
communication in humans is the synchronization of menstrual cycles among women
who live together, and the damping of irregularities in menstrual cycle length
by chemicals from males. However, in neither of these cases has the VNO been
clearly implicated. The arguments for and against a functional human VNO have
been explored in a recent review (Meredith2001). (See Extended-text
for further details, Mammalian Vomeronasal
Organ or Snake Vomeronasal Organ (Jacobson's
Organ) for additional illustrations).