[K2]: Signaling networks that control synapse development and cognitive function

Mammals can perceive a vast array of odor chemicals in the external world. We found that odor detection in the nose is mediated by ~1000 odorant receptors (ORs). The ORs are used combinatorially to encode odor identities, allowing discrimination of a multitude of odorants. We have asked how the nervous system translates these combinatorial codes into odor perceptions. We found that each sensory neuron in the nose expresses a singleORgene.Neuronswith differentORs are randomly interspersed in the nose, but their axons synapse in OR-specific glomeruli in the brain’s olfactory bulb, creating a stereotyped map ofOR inputs.We discovered another stereotypedmap ofOR inputs at the next level of the olfactory system, the olfactory cortex, but here inputs from different ORs partially overlap. Moreover, single cortical neurons receive multiple different OR inputs, potentially allowing integration of the components of an odorant’s combinatorial receptor code, and thereby a first step in the reconstruction of an odor image from its deconstructed features. In the cortex, individual odorants are represented by small subsets of neurons that are sparsely distributed over a relatively large area, but have similar patterns in different individuals. We recently found that binary odorant mixtures stimulate cortical neurons beyond those activated by their component odorants. This is consistent with a model in which cortical neurons act as coincidence detectors whose activation requires combinatorial OR inputs.