Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth

Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity.     

Targeting of olfactory neurons

Olfactory sensory neurons detect an enormous variety of small volatile molecules with extremely high sensitivity and specificity. The actual recognition and discrimination of odorous compounds is accomplished by specific receptor proteins located in the ciliary membrane of the sensory neurons. Axonal connections into the olfactory bulb, the first relay station for odor processing in the brain, are organized such that all neurons expressing the same odorant receptor converge their axons onto common glomeruli which are located at similar positions in all individuals from one species. For the establishment of this precise targeting of olfactory axons to their appropriate glomeruli, combinatorial functions of axon-associated cell adhesion molecules and odorant receptor proteins appear to be required. Odorants that stimulate distinct receptor cell populations will thereby activate a specific combination of glomeruli in the bulb; this characteristic activity pattern may be used by the system to encode the quality of a particular odorant.     

Electron microscopic observations on the olfactory mucosa of the cat

Résumé L'ultrastructure de l'épithélium olfactif du chat a été illustrée à l'aide d'observations avec le microscope électronique. L'auteur décrit les récepteurs olfactifs, les cellules de soutien et les cellules basales en soulignant quelques particularités de leur structure.      

Carnosine-like immunoreactivity in the primary olfactory neuron of the rat

Summary Using the peroxidase-antiperoxidase immunohistochemical technique, carnosine-like immunoreactivity was demonstrated to localize specifically within the primary olfactory neuron.This study was supported by grants from the Ministry of Education, Science and Culture, Japan (No. 61218016). Reprint requests to I. N., Department of Anatomy, School of Medicine, Fujita-Gakuen Health University, Toyoake, Aichi 470-11, Japan.     

Carnosine-like immunoreactivity in the primary olfactory neuron of the rat

Using the peroxidase-antiperoxidase immunohistochemical technique, carnosine-like immunoreactivity was demonstrated to localize specifically within the primary olfactory neuron.     

Neuronal plasticity and regeneration in the olfactory system of mammals: morphological and functional recovery following olfactory bulb deafferentation

The mammalian olfactory system has the unique property in the permanent turnover of the olfactory sensory neurons under normal conditions and following injury. This implies that the topographical map of the epithelium-to-bulb connections generated during ontogenesis has to be maintained despite neuron renewal in order to insure olfactory information processing. One way to investigate this issue has been to disrupt the peripheral connections and analyze how neural connections may be reestablished as well as how animals may perform in olfactory-mediated tasks. This review surveys the main data pertaining to both morphological and functional recoveries taking place in the peripheral olfactory system following olfactory bulb deafferentation. Conclusions from these studies are enlightened by recent data from molecular biology.     

Changes in olfactory perception during the menstrual cycle

The aim of the study was to find correlations between changes in olfactory sensitivity and the menstrual cycle. 14 young, healthy volunteers participated in the experiments. Subjects menstruated regularly and did not use oral contraceptives. Three odorants were investigated: phenylethyl alcohol, androstenone, and nicotine. Dilution series of the odorants were prepared, and presented to the subjects in order to determine the detection thresholds (triple forced choice). Additionally, the subjects' hedonic estimates of the odorants were measured, and mood states as well as hormonal levels of LH and estrogen were determined. Before the actual experiments started, subjects participated in three training sessions. One experiment was subdivided into 5 phases (two pre- and two postovulatory phases; one ovulatory phase). Only with regard to androstenone did trend analyses reveal a significant quadratic relationship between hedonic estimates and phases of the menstrual cycle, peaking at ovulation. Olfactory sensitivity was not significantly influenced by the menstrual cycle.     

Changes in olfactory perception during the menstrual cycle

Summary The aim of the study was to find correlations between changes in olfactory sensitivity and the menstrual cycle. 14 young, healthy volunteers participated in the experiments. Subjects menstruated regularly and did not use oral contraceptives. Three odorants were investigated: phenylethyl alcohol, androstenone, and nicotine. Dilution series of the odorants were prepared, and presented to the subjects in order to determine the detection thresholds (triple forced choice). Additionally, the subjects' hedonic estimates of the odorants were measured, and mood states as well as hormonal levels of LH and estrogen were determined. Before the actual experiments started, subjects participated in three training sessions.One experiment was subdivided into 5 phases (two pre- and two postovulatory phases; one ovulatory phase). Only with regard to androstenone did trend analyses reveal a significant quadratic relationship between hedonic estimates and phases of the menstrual cycle, peaking at ovulation. Olfactory sensitivity was not significantly influenced by the menstrual cycle.     

Neural map formation in the mouse olfactory system

In the mouse olfactory system, odorants are detected by ~1,000 different odorant receptors (ORs) produced by olfactory sensory neurons (OSNs). Each OSN expresses only one functional OR species, which is referred to as the “one neuron–one receptor” rule. Furthermore, OSN axons bearing the same OR converge to a specific projection site in the olfactory bulb (OB) forming a glomerular structure, i.e., the “one glomerulus–one receptor” rule. Based on these basic rules, binding signals of odorants detected by OSNs are converted to topographic information of activated glomeruli in the OB. During development, the glomerular map is formed by the combination of two genetically programmed processes: one is OR-independent projection along the dorsal–ventral axis, and the other is OR-dependent projection along the anterior-posterior axis. The map is further refined in an activity-dependent manner during the neonatal period. Here, we summarize recent progress of neural map formation in the mouse olfactory system.     

Accumulation of taurine in the nasal mucosa and the olfactory bulb

Using whole-body autoradiography of 14C-taurine in mice we have observed a high concentration in the nasal mucosa followed by accumulation in the olfactory bulb at longer survival times. When 14C-taurine was administered in the nasal cavity unilaterally, a high accumulation was observed in the ipsilateral olfactory bulb.     

Electroencephalography of the olfactory bulb in relation to prespawn homing

Summary remarks It is evident that the bulbar EEG is a complex response which can be influenced by several methodological and stimulant variables. What EEG patterns tell us about actual behavior remains obscure. The bulbar EEG which is evoked by homestream water is not necessarily a reflection of olfactory memory. The evoked bulbar EEG also does not necessarily demonstrate the salmon has distinguished the home-water from another water in terms of migrational orientation. Despite lack of absolute specificity, a correlation between bulbar EEG and actual behavioral performance has been observed even though some non-home waters evoke responses similar to that of the home water. In general it has been found that the home water response can be distinguished from the response to other natural waters. Failure to obtain complete specificity may be due to a variety of variables which have been alluded to earlier in this section. Thus considering that the evoked EEG is a reflection of the integration of a diverse afferent input, further electrical and computer analyses may eventually permit the decoding of the EEG in terms of behavior. However, if the EEG proves to be more a quantitative rather than qualitative reflection of brain activity, relating EEG to behavior will prove to be of limited value. Since afferent responses in the olfactory bulb are influenced by impulses from higher brain centers, studies on centrifugal aspects during olfactory stimulation may be useful in gaining some qualitative understanding of the home water evoked EEG of the olfactory bulb.     

External nares and olfactory perception

Lower vertebrates have more widely separated external nares than higher forms and are thus better adapted to utilize olfactory tropotaxis, or stereolfaction, than higher vertebrates which, on account of their flexible necks, must utilize klinotaxis. Snakes and tubenosed bats break the rule on account of their specialized life styles.     

External nares and olfactory perception

Summary Lower vertebrates have more widely separated external nares than higher forms and are thus better adapted to utilize olfactory tropotaxis, or stereolfaction, than higher vertebrates which, on account of their flexible necks, must utilize klinotaxis. Snakes and tubenosed bats break the rule on account of their specialized life styles.     

Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions

The growth and guidance of primary olfactory axons are partly attributed to the presence of olfactory ensheathing cells (OECs). However, little is understood about the differences between the subpopulations of OECs and what regulates their interactions. We used OEC-axon assays and determined that axons respond differently to peripheral and central OECs. We then further purified OECs from anatomically distinct regions of the olfactory bulb. Cell behaviour assays revealed that OECs from the olfactory bulb were a functionally heterogeneous population with distinct differences which is consistent with their proposed roles in vivo. We found that the heterogeneity was regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolished the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell–cell recognition.     

Determination of the connectivity of newborn neurons in mammalian olfactory circuits

The mammalian olfactory bulb is a forebrain structure just one synapse downstream from the olfactory sensory neurons and performs the complex computations of sensory inputs. The formation of this sensory circuit is shaped through activity-dependent and cell-intrinsic mechanisms. Recent studies have revealed that cell-type specific connectivity and the organization of synapses in dendritic compartments are determined through cell-intrinsic programs already preset in progenitor cells. These progenitor programs give rise to subpopulations within a neuron type that have distinct synaptic organizations. The intrinsically determined formation of distinct synaptic organizations requires factors from contacting cells that match the cell-intrinsic programs. While certain genes control wiring within the newly generated neurons, other regulatory genes provide intercellular signals and are only expressed in neurons that will form contacts with the newly generated cells. Here, the olfactory system has provided a useful model circuit to reveal the factors regulating assembly of the highly structured connectivity in mammals.     

An efferent respiratory modulation demonstrated in the olfactory bulb of the rat

The multiunit activity from mitral cells in the Rat olfactory bulb is modulated according to the respiratory cycle. Respiration and neuronal activity still coincide in tracheotomized animals, provided the olfactory peduncle is left intact.