Recent work has shown that the physiological implications of continual olfactory receptor replacement are profound. Most of the previously published results of studies of receptor mechanisms and of coding in the primary neurons will require reevaluation. It now appears that there are two classes of receptor neurons which respond differently to chemical stimulation, the recently differentiated neurons and the mature neurons. The differences reside in the membranes of the cilia and in the capacities of the cells for spike generation. These experiments will determine the differences in response properties of the two cell types and how their responses combine in the stimulus-evoked electro-olfactogram (EOG) and epithelium impedance change. The experiments measure responses to chemical stimulation at different stages during epithelial regeneration following nerve section and necrosis ablation. The changing proportions of the different cell types during this process allows determination of the contributions of each to the response. The reasons for complex EOG waves, for two independent components of the impedance change, and for simple and complex types of single-cell spikes have never been determined. These experiments test the hypothesis that these complex responses result from simultaneous activities in different cell types. The ionic mechanisms contributing to the EOG and the impedance change will be determined using ion replacement in the isolated receptor organ. Differences in ionic components of action potentials at different stages of neuron maturity will be explored using ion replacement on tissue slice preparations. An attempt will be made to block mitosis during regeneration to produce an epithelium with cells of homogeneous maturation state. Such a preparation would simplify experimental studies and clarify their interpretation. Olfactory receptors are unique among neurons of the vertebrate nervous system in their capacity for renewal. This work will further our knowledge of the processes which occur in these cells and the mechanisms which account for the olfactory sense.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000352-06
Application #
3216647
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1985-09-01
Project End
1992-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Kleene, S J; Pun, R Y (1996) Persistence of the olfactory receptor current in a wide variety of extracellular environments. J Neurophysiol 75:1386-91
Kleene, S J (1995) Block by external calcium and magnesium of the cyclic-nucleotide-activated current in olfactory cilia. Neuroscience 66:1001-8
Kleene, S J (1994) Inhibition of olfactory cyclic nucleotide-activated current by calmodulin antagonists. Br J Pharmacol 111:469-72
Kleene, S J (1993) Origin of the chloride current in olfactory transduction. Neuron 11:123-32
Kleene, S J (1992) Basal conductance of frog olfactory cilia. Pflugers Arch 421:374-80
Kleene, S J; Gesteland, R C (1991) Transmembrane currents in frog olfactory cilia. J Membr Biol 120:75-81
Kleene, S J; Gesteland, R C (1991) Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 11:3624-9
Pun, R Y; Gesteland, R C (1991) Somatic sodium channels of frog olfactory receptor neurones are inactivated at rest. Pflugers Arch 418:504-11