Harvard University - Department of Molecular & Cellular Biology


by Amy Gresser and Catherine Dulac

June 1st, 2006

Authors Amy Gresser and Catherine Dulac
When animals meet, how do they distinguish friend from foe? Such determinations must be made quickly, since any delay could mean a missed opportunity, but also accurately, since mistaking an enemy for a potential mate could have dire consequences. One way that animals communicate with each other is through the use of pheromones, chemical cues that carry information about the species, gender, and social status of the animal that produced them. When detected by another animal of the same species, pheromones trigger stereotyped, preprogrammed responses. These responses can be behavioral, such as the initiation of courtship or aggression, or they can affect the animal’s internal state, such as the changes in hormone levels associated with the onset of puberty. In this way, pheromones act as a sort of chemical language that both describes the producer and defines the response of the receiver.

Because responses to pheromones play such a critical role in the lives of animals and their interactions with others, a great deal of research has focused on trying to understand the nature of pheromonal compounds and how their detection is translated into specific responses. The vomeronasal organ (VNO), a pair of tubular structures located at the base of the nasal cavity, is thought to be specialized for the detection of pheromones. Neurons in the VNO each express a single type of receptor molecule from among a set of approximately 200 different members. A particular pheromone binds to only one or a few types of receptors similar to the way a specific key can open only one or a few locks. When pheromones bind to receptor molecules on a particular VNO neuron, the neuron is activated and a set of chemical changes begins that transmits the activation signal to connected neurons in the network. The main group of connected neurons consists of the mitral cells, which are located in a small region near the front of the brain known as the accessory olfactory bulb (AOB). These neurons, in turn, connect directly to areas of the amygdala, a part of the brain involved in the generation of unconscious responses.

In a set of experiments published in the June 1 issue of Neuron (Wagner et al., 2006), we examined connections between VNO neurons and mitral cells in an effort to better understand how the signaling network is organized within the AOB. By analyzing the relative locations of these connections, we found that the identity of the receptor expressed by a neuron plays a critical role in determining where connections will occur and that neurons expressing similar receptors will form connections that are clustered together in specific regions of the AOB. We also determined that each mitral cell makes connections to multiple VNO neurons that express different, but closely related, receptors.

These results suggest that the AOB is organized according to a spatial map, and they have important implications for our understanding of pheromonal signaling. First, they imply that signals arising from neurons that express different receptors, which would likely bind different pheromones, may be integrated in the AOB. Such signal integration at an early point in the neuronal network could be beneficial since pheromone-related responses occur without conscious brain processing and, as a result, there are few later sites where integration could occur. Second, the organization seen in the AOB hints that blends of pheromones, rather than single compounds, may be necessary to trigger responses. Since pheromone-induced responses are often costly to an animal from a health or safety standpoint, it is critical that an animal respond appropriately and only when truly necessary. A reliance on blends could introduce redundancy into the system and thereby ensure that responses occur solely when multiple signaling cues are detected.

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