Abstract: The projection targets of the olfactory bulb in pigeons and turtles were investigated using autoradiographic techniques. Despite the relatively smaller size of the olfactory bulbs in pigeons, the projection targets of the olfactory bulb are very similar to those in turtles. In both pigeons and turtles, the olfactory bulb projects to the entire rostrocaudal extent of a portion of the dorsolateral telencephalon (which is here recognized as the pyriform cortex in both birds and reptiles) and to portions of the medial telencephalic wall including the medial septal region. In addition, a projection to the olfactory tubercle of the ventral telencephalon is clearly present in turtles and also appears to be present in pigeons. Pigeons and turtles do differ significantly, however, in the extent of the projection to the amygdaloid region. In turtles, olfactory bulb input encompasses the entire mediolateral and rostrocaudal extent of the amygdaloid region, while in pigeons the input is restricted to a small dorsomedial portion of the amygdala termed nucleus taeniae of the archistriatum. The present results suggest that the olfactory bulb projections in birds are generally similar to those in reptiles, with the exception that secondary olfactory bulb projections to the amygdala may be much reduced in birds compared to those in reptiles. The functional significance of the reduction in olfactory input to the amygdala is presently uncertain.

Abstract: By a phenomenon called primary neural induction, the competent cubic epithelium of the ectoderm becomes the vertebrate nervous system upon contact with the roof of the a r c h e n t e r ~ n . ~ ~ . ~ ~ The simple cubic epithelium of the ectoderm gives origin subsequently to different populations of neurons which acquire such extreme morphologic and functional complexity that generalization about their behaviors requires great caution. Although some of the basic epithelial characteristics are maintained in the adult nervous system,52 the capacity to repair cellular losses is greatly impaired.8y10,34 On the other hand, in a system where specific cell recognition and storageretrieval of information are of paramount importance, anatomic stability of the cellular elements, after development, has been always considered essential. Consequently, the characterization of the neurons as perennial elements, first put forward by Bizzozero' in 1894, has been widely accepted until r e ~ e n t l y . ~ ~ ~ ~ ~ It was also established that in the central nervous system of mammals not only were neurons irreplaceable, but also severed axons could not regrow because of the intrinsic inability of the damaged central perikarya to sustain regeneration of their axons. The inability of the mammalian CNS to sustain recovery has been recently challenged by a number of new observations. Postnatal development of microneurons from the subependymal regions of the brain has been documented in rodent^.^-^-',^^ Transplantation experiments, resumed after the pioneering work done at the beginning of this ~en tu ry ,~* '~* ' ' have shown that lesioned neuronal populations can be substituted in selected brain region^.^.'^,^ 7 , 3 7 The phenomenon of sprouting4o360 and the capacity of the central neurons to regrow their axons when proper environment is provided l , I 7 have challenged the well-established rule proposed by Arnemann6 since 1787 that regrowth of nerve fibers cannot occur in the postnatal central nervous system. Even if reestablishment of new circuitries with recovery of function has not been so far obtained in mammals, the new observations have great practical and theoretical importance and provide hope for unsuspected capacity of repair of the nervous system. Furthermore, these results

Abstract: In 1962, Altmanl proposed that neurogenesis takes place in the cerebral cortex of adult rats. Between 1963 and 1969, Altman and coworkers found adult and juvenile neurogenesis to be especially prominent in the granule cell populations of both the hippocampus and olfactory Kaplan and Hinds” subsequently showed that these newly formed cells had the ultrastructural characteristics of neurons. In the meantime, Bayer and Altman” obtained circumstantial evidence that the number of granule cells in the hippocampus was increasing in the adult period, while Roselli-Austin and Altman” found the number of granule cells in the olfactory bulb to remain constant during adult life. This paper summarizes recent comparing the patterns of adult neurogenesis in these two populations of the rat brain.

Abstract: A monoclonal antibody (Mab) has been developed which recognizes a family of cell surface glycoproteins found in high levels of rat olfactory receptor neurons. This Mab, designated 2B8, was produced by the fusion of X63-Ag8.653 myeloma cells and spleen cells of a mouse immunized with PC12 rat pheochromocytoma cells. Immunofluorescence analyses of cryostat sections of neonatal olfactory epithelium show prominent 2B8 binding to receptor neurons. Within the olfactory bulb only the glomerular and olfactory nerve layers show 2B8 binding. All other neural structures in the main olfactory bulb have background levels of reactivity. Analyses of 2B8 binding to particulate protein preparations from several central and peripheral nervous system components demonstrated highest 2B8 antigen specific activity in olfactory bulb and epithelium and detectable levels in dorsal root ganglia (DRG), whole cerebrum, cerebellum, and brainstem. However, 2B8 antigen could not be detected in non-olfactory structures by immunofluorescence. Some non-neural tissues also had the ability to bind 2B8 Mab in the particulate protein radioimmunoassay. In order to compare the 2B8-reactive molecules found in each tissue, Mab was applied to polyacrylamide gels of unlabeled membrane proteins. A family of molecules with diverse molecular weights was found. Some were unique to individual tissues whereas others were shared among tissues. Olfactory bulb and epithelium had a unique band with Mr = 215,000 and another band with Mr = 142,000. The 142,000-dalton band was also found with PC12 cells. PC12 cells also had several bands of lesser molecular weight, including 51,000 and 43,000. Testes membranes had immunoreactive bands only at Mr = 46,000 and 43,000. Bone marrow, perinatal liver, and DRG each expressed a single 2B8-reactive band with Mr = approximately 114,000. Salivary gland had four reactive bands, two common to it and only PC12 cells, the 114,000-dalton band which is similar to that found in adult rat bone marrow and DRG, and a unique band at Mr = 152,000. 2B8 immunoprecipitates of olfactory bulb and epithelium were analyzed for glycosyl groups by lectin reactivity. Wheat germ agglutinin and Ricinus communus agglutinin I bound the 2B8 antigens using two distinct assay methods. This suggests that the 2B8 antigens recognized in the olfactory system are glycoproteins having sialic acid and D-galactosyl components.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract: Serial sections of 13 embryos and fetuses of the harbor porpoise from 10 mm crown-rump length up to 167 mm total length were studied. Unlike the adult animals, ontogenetic stages of 18-27 mm crown-rump length still show a typical mammalian olfactory bulb. The olfactory bulb primordium is penetrated by olfactory nerve fibers, the latter passing through the cribriform plate. However, the olfactory bulb anlage is gradually reduced in later stages, its placodal component being largely uncoupled from the telencephalon. As a ganglionlike structure, the remains of the placodal component stay in contact with the nasal septum and mucosa via thin bundles of nerve fibers. The ganglion and plexus can be traced within the meninges until the adult stage of the porpoise. There is strong evidence that they represent the material of the terminalis system, which cannot be distinguished from the olfactory system in earlier stages. A vomeronasal organ could not be detected in the embryonal and fetal material investigated.

Abstract: The immunohistochemical characteristics of the human olfactory system were (OMP). OMP was detected in the olfactory receptor neurons and processes extending from the olfactory neuroepithelium to the olfactory bulb. The olfactory receptor cells located close to the epithelial surface also contained OMP. In severely degenerate regions, only a few OMP-containing cells were observed. Differences in OMP-staining intensity were noted among the olfactory receptor cells. The thick neuroepithelium. Proliferating olfactory neuroepithelium contained OMP reactive and nonreactive olfactory receptor cells. The presence of OMP reactive and nonreactive olfactory neurons indicates the coexistence of two functionally different phases of olfactory neurons. These findings suggest that continuous cell turnover is occurring in human olfactory neuroepithelium.

Abstract: The pattern of output of mitral and tufted cells of the rat olfactory bulb (OB) to layer Ia overlying the pars externa (pE) of the anterior olfactory nucleus (AON) has been studied in the rat by iontophoresis of horseradish peroxidase and Phaseolus vulgaris-leucoagglutinin. These agents labeled mitral and tufted cells and at least the proximal portion of their axons. In most cases we observed small branches from axons of the lateral olfactory tract that appear to terminate in the region of the pE AON, while the main axon could often be traced for considerable distances past these branches. These branches are assumed to terminate in the pE AON because they could not be traced to other terminal regions, because they ramify in layer Ia, and because they usually show small swellings characteristic of axons in terminal regions. Although each ramification could be extensive, we found that the positions of these small branches were related to the positions of the injections within the OB. Dorsal medial injections labeled dorsal branches. Ventral medial injections labeled ventral branches. Injections on the lateral face of the OB labeled intermediate branches. The centers of the regions within which branches were labeled were strongly correlated with the positions of the injection around the circumference. Comparison of the anterior-posterior axis of the OB produced no such strong correlation. Reconstructions of axons showed that terminal branches arise from both mitral and tufted cells, although at least some mitral cells are shown not to have such branches in the pE AON. Studies of the patterns of dendrites and terminals in the pE AON indicate that this region has the same pattern of layer Ia and Ib terminals seen in other olfactory cortical regions. The pE AON cell layer is intercalated just below the boundary between layers Ia and Ib. Since dendrites of the underlying pars lateralis of the AON (pL AON) penetrate into layer Ia over much of the pE AON, it is necessary to remember that at least part of the pL AON may also receive topographically organized inputs.

Abstract: • Ultrastructural alterations were present in biopsy specimens of olfactory epithelia taken from two patients with anosmia. In both cases, the olfactory epithelia presented a disorganized appearance when viewed by transmission electron microscopy. The number of ciliated olfactory receptors was reduced; few olfactory vesicles were present at the epithelial surface. Where present, the olfactory vesicles usually lacked cilia. Since both patients had a history of head trauma, we speculate that the fila olfactoria may have been severed at the level of the cribriform plate. The histopathologic changes in the olfactory receptors that were revealed by electron microscopy may have resulted from the inability of regenerating axons to reach their normal site of synaptic contact—the second-order neurons (mitral cells) in the olfactory bulb of the brain. (Arch Otolaryngol1985;111:122-126)

Abstract: The ciliated dendritic bulb of the olfactory neuron of the bullfrog was studied with the electron microscope, with emphasis on microtubular elements. Methods used included various fixation procedures with and without detergent extraction, serial sectioning, microtubule polarity assays, and an assay to demonstrate F-actin. Structural continuity exists, via microtubules, between the ciliary membrane and the perikaryon of the neuron. One type of structural link connects the distal end of the basal body to the plasma membrane and, in slightly oblique cross sections of the basal body, the link shows a highly characteristic tripartite profile resembling a claw hammer. The six to ten basal bodies of a dendritic bulb have a lateral foot that serves as an organizing center for microtubules, and these microtubules (totaling about 150) extend toward the perikaryon in the basal half of the epithelium. Polarity assays indicate that the attached or minus ends of dendritic microtubules are in the dendritic bulb, with their plus or fast-growing ends near or within the perikaryon of the neuron. It is shown that dendritic microtubules are depolymerized by direct osmium tetroxide fixation, in contrast to olfactory axonal microtubules, which persist after such fixation. F-actin appears to be abundantly present in the dendritic bulb of the neuron, and it is possible that this actin could play a role in shape changes of the dendrite. The various findings provide new information about the olfactory dendrite, its microtubule organizing centers, and the nature and relationships of its microtubules.

Abstract: Previous studies have quantified growth and atrophy of the olfactory bulb and olfactory epithelium of the Sprague-Dawley rat from maturity to senescence. Major events occurring in these structures include changes in the volume of mitral cells and changes in the number of septal olfactory receptors. These effects are large, consist of a growth phase followed by atrophy, and are temporally related in that events in the olfactory epithelium precede those in the mitral cells. A hypothesis of aging based on transneuronal effects would predict that these changes would be similarly transmitted to the next synaptic station in the olfactory pathway. Therefore, cells and synapses of the piriform cortex were studied in rats 3, 12, 18, 24, 27, 30, and 33 months of age. Alternate Vibratome sections through brains perfused with mixed aldehydes were processed for light and electron microscopy. No significant age effects were found for the volumes of cortical laminae Ia and Ib. Both numerical and surface density of synaptic apposition zones in layer Ia, formed primarily by mitral cell axons, were stable with age. A modest (18%) but significant decline in the proportion of layer Ia occupied by dendrites and spines was mirrored by an increase in the proportion of glial processes; no change in the proportion of axons and terminals was observed. Neither nuclear volume, nor soma volume, nor numerical density of layer II neurons changed with age. Thus, contacts made in the piriform cortex by mitral cell axons remain relatively stable in senescence, despite the marked volumetric changes in the mitral cell somata, changes which were confirmed again in this study. Age-related dendritic regression in layer II neurons may be attributable to functional deafferentation subsequent to reduced receptor input to mitral cells.

Abstract: Ultrastructural studies of single and serial sections of bullfrog olfactory axons showed that smooth endoplasmic reticulum (SER) tubules, which usually appear as single profiles in cross-sections of axons, are continuous over considerable distances, but that discontinuities do exist. Computer-assisted three-dimensional reconstruction of portions of axons indicated that the SER tubules show considerable variation in the volume of the cisternal space along the tubule, which often follows a tortuous path. Some branching and anastomosing appears to occur, and electron-dense material was present in the cisternal space of some tubules. SER tubules are often bridged to neurofilaments and less often to microtubules. The usual two to three microtubules in the axoplasm form a domain which is characterized by a clear area, or zone of exclusion, around the microtubules. Ultrastructural cytochemistry was used to demonstrate that SER tubules actively sequester Ca. The electron-dense product (calcium oxalate) was uniformly and specifically associated with the SER of axons at both proximal (closest to the perikarya in the olfactory epithelium) and distal (closest to the olfactory lobe of the brain) ends of the olfactory nerve. It is concluded that the primary function of SER tubules in these axons is to serve in the regulation of Ca in the axoplasm, probably to facilitate fast axoplasmic transport, and that a secondary function may be the translocation of material in the cisternal space. The observations are discussed as they may relate to the “microstream” hypothesis of axoplasmic transport, and it is argued that fast transport occurs through the zone of exclusion associated with the microtubule domain(s) of axons.

Abstract: In Experiment 1, rats with posterior lateral olfactory tract/anterior amygdala lesions or with control neocortical lesions were tested for retention of a preoperatively learned odor detection task and for learning on new odor discrimination problems. All rats had perfect or near-perfect retention of the detection task, and there were no discernible differences between groups in learning on the new odor discrimination problems. In Experiment 2, an intensity-difference threshold for olfaction was determined in 4 rats before and after lesions of the posterior lateral olfactory tract and anterior amygdala. There were no apparent differences between pre- and postoperative performances on this psychophysical test. These results indicate that lateral olfactory tract projections to the amygdala and posterior olfactory cortex are not essential for normal performance on simple olfactory discrimination tasks.

Abstract: 1. The electrical activity of the two olfactory receptor neurons in individual pheromone-sensitive sensilla on the antennae of male cabbage looper moths (Trichoplusia ni) was monitored extracellularly. Responses to single and multiple component stimuli containing up to three of the seven behaviorally active compounds for this species were obtained at several different stimulus intensities. 2. Neurons which produced large amplitude action potentials (A neurons) were more responsive to (Z)7-dodecenyl acetate, a major component of the female pheromone gland, than were their companion B receptor neurons. B receptor neurons were more responsive to (Z)7-dodecenol, a behavioral inhibitor of male orientation to calling females. Neither neuron was particularly responsive to stimuli containing only dodecyl acetate, a minor component of female glands, which has powerful synergistic effects on male behavior. 3. Some blends of these three compounds elicited responses which were not readily predicted from a knowledge of the cells' responses to individual components of the blend. 4. The average A receptor neuron was significantly more responsive to the blend containing (Z)7-dodecenyl acetate and 10% dodecyl acetate than it was to either component alone or, for that matter, to the algebraic sum of their individual responses. These enhancements were intensity-dependent, occurring to a significant extent only in the middle portion of a neuron's dose-response function. Although A recpetor neurons are not particularly responsive to either (Z)7-dodecenol or dodecyl acetate, a binary mixture of these components elicited significantly smaller responses than expected. Blends which contained all three compounds elicited responses in A receptor neurons which were also significantly smaller than those expected. These reductions were dose-dependent and occurred most reliably at the middle of the dose-response function. 5. The responses of B receptor neurons to blends were more variable than those obtained simultaneously in A receptor neurons. Although all of the various alterations in discharge magnitude observed in the typical A receptor neuron response to blend stimulation were seen in some fraction of the B receptor neurons sampled, only the trinary blend elicited responses which were significantly different from those expected. These reductions in the response of B receptor neurons were also intensity-dependent because they were more reliably observed in the middle portion of the neurons' dose-response function. 6. The sensory processing of complex chemical signals by the insect olfactory system has been postulated to involve a set of narrowly tuned, highly specific olfactory receptor neurons, one for each of the behaviorally relevant component compounds in the pheromone blend. Here we show that olfactory receptor neurons may also be responsive in unique ways to multiple component stimuli even in cases where an individual behaviorally relevant pheromone component is not processed by a separate class of receptor neuron.

Abstract: The fish anaesthetic tricaine methanosulfate destroyed the cilia on olfactory sensory epithelia of channel catfish, when fish were exposed to tranquilizing doses of the drug. Cilia on the non sensory epithelium appeared to be unaffected by multiple exposures of the drug. Sensory cilia regenerated within 28 days after exposure.

Abstract: Monoclonal antibody (mAb) 5B4 recognizes in the rat a large, developmentally regulated membrane glycoprotein. The larger form of this antigen (185-255 kD) occurs in the developing nervous system and is present in membranes of nerve growth cones, as determined by analysis of a growth cone particle fraction. An immunochemical characterization of this antigen and of a smaller form (140 kD), sparsely present in the mature nervous system, has been described (Ellis, L., I. Wallis, E. Abreu, and K. H. Pfenninger, 1985, J. Cell. Biol., 101:1977-1989). The present paper reports on the localization by immunofluorescence of 5B4 antigen in cultured cortical neurons, developing spinal cord, and the mature olfactory system. In culture, mAb 5B4 stains only neurons; it is sparsely present in neurons at the onset of sprouting while, during sprouting, it appears to be concentrated at the growth cone and in regions of the perikaryon. In the developing spinal cord, 5B4 labeling is faintly detectable on embryonic day 11 but is intense on fetal day 13. At this stage, the fluorescence is observed in regions of the cord where axonal growth is occurring, while areas composed of dividing or migrating neural cells are nonfluorescent. With maturation of the spinal cord, this basic pattern of fluorescence persists initially, but the staining intensity decreases dramatically. In the adult, faint fluorescence is detectable only in gray matter, presumably indicating the presence of the 140 kD rather than the fetal antigen. The only known structure of the adult mammalian nervous system where axonal growth normally occurs is the olfactory nerve. mAb 5B4 intensely stains a variable proportion of olfactory axons in the mucosa as well as in the olfactory bulb. Based on both immunochemical and immunofluorescence data, the 5B4 antigen of 185-255 kD is associated specifically with growing neurons, i.e., neurons that are generating neurites.

Abstract: Electroencephalographic olfactometry and behavioral olfactometry were developed to evaluate objectively the olfactory function of 12 dogs. These techniques were used to determined normative thresholds for benzaldehyde, a mixed olfactory and trigeminal stimulant, and eugenol, a suspected pure olfactory stimulant, in 12 dogs. Both techniques were effective in obtaining a mean threshold for clinically normal dogs. Electroencephalographic olfactometry was demonstrated to be more sensitive than was behavioral olfactometry. The techniques measured olfactory function by failure to evoke responses in dogs after ablation of olfactory mucosa. The contribution of trigeminal stimulation to the thresholds was not determined.