Burton M. Slotnick - US grants

Following axotomy, olfactory receptor cell neurons degenerate and then regenerate forming new axonal connections with the central nervous system tissue dorsal to the cribriform plate. If portions of the olfactory bulb are left intact, connections are established but the anatomical arrangement of glomeruli and mitral cells is highly abnormal. If not all axons are disconnected during surgery, the part of the bulb which the preserved axons innervate retains some normal morphology. Our preliminary studies have shown that regenerated olfactory axons of rats bulbectomized when neonates form new and aberrant connects in the forebrain but are unable to detect odors. However, if a remnant of disconnected bulb is left in place, it is reinnervated by olfactory cell axons and such animals are capable of detecting and discriminating odors. The purpose of the proposed research is to replicate and expand these findings. Behaviorally, the classes of odors tested will be expanded, and both the degree of sensitivity and the ability to discriminate among odors will be studied. These behavioral data will then be correlated with the anatomical organization of the olfactory bulb remnant, its innervation pattern, immunohistochemical and electron microscopic assessment of the olfactory reconnection, and with the afferent and efferent connections of the bulb remnants as compared with the normal situation. The experiments are designed to gain further information relating to the plasticity of the system and to the underlying mechanisms involved in olfactory processes of odor detection and recognition, particularly with regard to the proposed idea of topography in the system.

DESCRIPTION: (provided by applicant) The proposed studies will use behavioral and anatomical methods to examine potential mechanisms of odor quality coding at the level of the olfactory bulb in rats. Because perception of odor quality cannot be assessed using traditional odor detection and odor discrimination tasks, we propose using more sophisticated methods that allow rats to report on their recognition of individual components of a homologous series of odors (a recognition test using odor memory) and their classification of novel odors from different homologous series (a modified odor generalization test). The extent to which odor quality coding depends upon a discrete odotopic map will be assessed by testing rats with selective aspiration lesions or selective olfactotoxin-induced deafferentation of the bulb on odor recognition tasks. Behavior tasks will use precision olfactometry. Anterograde transport of horseradish peroxidase will be used to assess connections between the olfactory epithelium and olfactory bulb in experimental rats.

The proposed studies will use behavioral methods to assess deficits in taste detection, discrimination, taste sensitivity, and taste preference in rats with lesions of thalamic, amygdala, and neocortical taste centers of the forebrain. Behavioral tests are designed to provide separate measures of sensory (gustatory) capacity and hedonic value of tastants. For detection, discrimination and psychophysical tests, rats will be trained on an operant task in which tastants provide cues for discriminative responding. To assess taste preferences, rats are trained on a free operant choice procedure. A second experiment will test the effects of gustatory neocortical lesion on memory for tastes. In general, these experiments are designed to evaluate the hypothesis that the thalamic- neocortical taste system plays an important role in fine discriminative performance while the taste projections to the amygdala are important in determining the hedonic value or tastants.

taste; sensory mechanism; psychophysics; olfactions; food flavor; neural information processing; neocortex; avoidance behavior; acetates; thalamic nuclei; limbic system; olfactory lobe; amygdala; frontal lobe /cortex; chemical stimulation; sweetening agents; neuroanatomy; water solution; olfactory stimulus; operant conditionings; sensory discrimination; behavior test; laboratory rat; experimental brain lesion;

Sensory cells in the nose respond to odors and send signals back to the olfactory bulb of the brain. These cells live for only a few weeks and, when they die, they are replaced by maturing cells from a germinal cell layer in the olfactory tissue. The maturing cells extend their axons into the olfactory bulb where they replace the contacts made by the axons of the dying neuron. The ability of the olfactory receptor epithelium to reconstitute itself in this fashion is unique because neurons in other sensory systems are not replaced if they die. Of particular interest is the fact that if the olfactory bulb is removed, the axons of maturing sensory neurons will continue to grow until they reach brain tissue. They will then make synaptic contact with neurons that do not normally receive inputs from olfactory receptor cells.
While this remarkable example of neural plasticity has been demonstrated in anatomical
studies, it remains unclear whether these new synaptic contacts can be used by the brain to support the sense of smell. We propose to examine this issue by removing the olfactory bulb in neonatal rats and testing their ability to detect and discriminate odors when they are adults. Operated rats will be trained in a precision olfactometer device to determine their odor sensitivity and whether they can discriminate among odors. Behavioral results will be correlated with an anatomical analysis of forebrain connections originating from the olfactory bulb. A positive outcome would provide evidence for a hitherto unrecognized ability of the brain to utilize novel information and translate it into conscious sensory signal

We propose to develop and validate tests to assess olfactory function in gene-targeted mice. A simple, rapid and reliable test for odor detection, will be used as a phenotyping assay for both odor detection and odor discrimination in strains of commercially available mice. More sophisticated behavioral measures, including assessing odor detection threshold, odor discrimination, odor memory and, of particular interest, odor quality recognition will also be developed. To facilitate within- and cross-strain comparisons of identified glomeruli, we will construct a metric atlas of the mouse olfactory bulb. All behavior tests will be computer-controlled and yield multiple objective measures of performance. The reliability of the behavioral tests will be established for each wild-type strain and will be defined by intercorrelations of dependent measures and by variance of outcomes among strains. A final report of these studies will incorporate a detailed description of apparatus, methods protocol and files of raw data and summary statistics presented in database and spreadsheet format.