Mice with a "monoclonal nose": perturbations in an olfactory map impair odor discrimination.

We have altered the neural representation of odors in the brain by generating a mouse with a "monoclonal nose" in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced 20-fold. We observe that these mice can smell, but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

Interchromosomal interactions and olfactory receptor choice.

The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence in situ hybridization (FISH) experiments allow us to visualize the colocalization of the H enhancer with the single OR allele that is transcribed in a sensory neuron. In transgenic mice bearing additional H elements, sensory neurons that express OR pseudogenes also express a second functional receptor. These data suggest a model of receptor choice in which a single trans-acting enhancer element may allow the stochastic activation of only one OR allele in an olfactory sensory neuron.

Both processing speed and semantic memory organization predict verbal fluency in schizophrenia.

We systematically examined the relationship of both lexical retrieval and semantic memory organization to categorical verbal fluency performance in 40 outpatient schizophrenic subjects and 16 healthy controls. Mean choice reaction time (RT) on a lexical decision task was used as a measure of lexical retrieval efficiency. The complexity of semantic memory organization was measured using a Pathfinder semantic network analysis (calculated as the number of inter-node links obtained from a similarity rating task). In the schizophrenia group only, RT and semantic network links were each significantly negatively correlated with fluency and, together, accounted for 23% of the variance in fluency. RT and links were not significantly correlated with one another. Findings were unrelated to age, sex, education, or medication dose. Controlling for IQ reduced but did not abolish the relationship between fluency and network links. We conclude that the restricted verbal output of schizophrenic subjects is related both to impaired lexical retrieval and to variation in semantic memory organization, which partly reflects general intelligence. The statistical independence of the retrieval speed and organizational factors suggests that individuals with schizophrenia differ in the underlying processes that contribute to their reduced verbal fluency.