The encoding and neural integration of molecular signals are processes which underline all nervous system functions. As a sensitive, broad-spectrum molecular (odor) detector, the sense of smell serves as a model system for studying neural molecular receptors, information processing in synaptic circuits, and regeneration. CNS regions involved in olfaction mediate life- sustaininq behaviors such as food finding and mate recognition in animals and are the sites of devastating pathologies that include epilepsy, schizophrenia, and Alzheimer's disease in humans. In addition, odor siqnals are detected by receptor neurons that have the unique capacity to reqenerate, thus demonstrating a degree of plasticity not seen in other mammalian neuronal systems. Despite the clinical and basic neurobiological importance of these properties, little is known about the neural processing of molecular odor information. The long term aim of this research is to understand how odors are encoded and integrated in the olfactory pathway. To elucidate these mechanisms, one must study how factory neurons function as both single elements and as cooperative members of synaptic networks when stimulated with odors. To this end, the salamander animal model and controlled odor stimulation methods were developed in this laboratory. This preparation has permitted precise correlation of odors with extra- and intracellular receptor and mitral/tufted unit responses, and has allowed the observation of odor-mediated behavior in the same experimental species. What are now needed are additional intracellular and ensemble recordings from the bulb and epithelium and a correlation of unitary responses, population responses, and circuitry structure. Here it is proposed that the salamander model be further exploited: l) to measure global odor-elicited responses in the bulb and epithelium with a new method for imaging voltage-sensitive dyes recently developed in this lab; 2) to record intracellular odor-elicited responses from identified periglomerular and granule cells in the bulb; 3) to define the neurochemical properties of the bulb using immunohistochemical methods; and 4) to correlate the unit and global responses, with the synaptic organization of the bulbal circuits. These studies should yield new data on the processing of molecular/odor information which are relevant to understanding the principles by which neural integration occurs in the olfactory pathway as well as in other regions of the brain.
