Unilateral Bulbectomy Research Articles

The Grueneberg olfactory organ neuroepithelium recovers after injury

The Grueneberg organ (also termed Grueneberg ganglion) is an olfactory subsystem at the rostral nasal septum of rodents, and has been suggested to exist also in humans. Grueneberg organ neurons respond to coldness and alarm pheromones, but the anatomical arrangement and regenerative capacity are not fully characterised. We examined the relationship between the glia and the neurons using crosses of two transgenic mouse lines, S100ß-DsRed and OMP-ZsGreen, to visualise olfactory ensheathing cells (OECs) and Grueneberg olfactory neurons, respectively. Within the epithelium, Grueneberg organ OECs were in direct contact with Grueneberg organ neuron cell bodies. Individual axons from the neurons initially grew over the surface of the OECs before forming larger fascicles consisting of numerous axons and OECs. Considering the location of the Grueneberg organ so close to the external environment, it may be that the Grueneberg neurons are likely to be subject to damage suggesting that as in other olfactory regions there is a capacity for recovery after injury. Here, we used a well characterised model of olfactory nervous system injury, unilateral bulbectomy, to determine whether Grueneberg organ neurons degenerate after injury. We found that Grueneberg organ neurons degenerated in response to the axotomy, yet by 11 days post injury neurons and/or axons were detected again within the epithelium. Our results demonstrate that while Grueneberg organ neurons and glia have a distinct relationship in the epithelium, they have largely similar characteristics to that of the main olfactory neurons and glia.

Combined VEGF/PDGF improves olfactory regeneration after unilateral bulbectomy in mice.

The olfactory receptor neurons lining the nasal cavity have a remarkable capacity to regenerate throughout life. They are replenished continuously and their axons make new connections within the olfactory bulb. However, some factors such as head trauma and skull base surgery damage the olfactory nerve which lead to olfactory dysfunction. Losing the sense of smell has considerable effects on quality of life and life-expectancy. Therefore, there is a clear need to find a treatment for olfactory dysfunction. One such potential treatment is growth factor therapy which showed promising results in the spinal cord and brain injuries. The aim of the present study was to investigate whether combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor treatment can improve the olfactory neurons regeneration in mice. The degeneration of the olfactory neurons was induced by unilateral bulbectomy. The treatment group received 1.5 µg of the combined growth factors intranasally, while the control injured group received saline. Growth factor treatment significantly increased the number of immature neurons at 5 and 7 days post injury and also the number of mature olfactory neurons at 10 and 14 days post bulbectomy. Regenerating axons extended over a larger volume in the operated cavity in the treatment group compared to control group at 14 days post bulbectomy. The growth factor treatment also significantly reduced astrocytic glia scar in the operated cavity. The results indicate that the combined delivery of the growth factors has the potential to improve olfactory dysfunction.

Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system.

During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or overproject into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However, it is unclear when phagocytosis by OECs first commences. We investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons, and S100β-DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at embryonic day (E)13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mistargeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.

Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice

Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life, however, it remains unclear how OECs respond to a major injury. We have examined the proliferation and migration of OECs following unilateral bulbectomy in postnatal mice. S100ß-DsRed and OMP-ZsGreen transgenic mice were used to visualize OECs and olfactory neurons, respectively, and we used the thymidine analogue ethynyl deoxyuridine (EdU) to identify cells that were proliferating at the time of administration. Following unilateral bulbectomy, there was an initial phase of OEC proliferation throughout the olfactory pathway with a peak of proliferation occurring 2 to 7 days after the injury. A second phase of proliferation also occurred in which precursors localized within the olfactory mucosa divided to replenish the OEC population. We then tracked the positions of OECs that had proliferated and found that there was a progressive increase in OECs in the cavity for at least 12 to 16 days after injury which could not be accounted for solely by local proliferation of OECs within the cavity. These results suggest that OECs migrated from the peripheral olfactory nerve to populate the mass of cells that filled cavity left by bulbectomy. Our results demonstrate that following injury to the olfactory nervous system, the OEC population is replenished by migration of cells that arise from both local proliferation of OECs throughout the olfactory nerve pathway as well as from precursor cells in the olfactory mucosa.

Microvillous cells expressing IP3 receptor type 3 in the olfactory epithelium of mice

Microvillous cells of the main olfactory epithelium have been described variously as primary olfactory neurons, secondary chemosensory cells or non-sensory cells. Here we generated an IP3R3(tm1(tauGFP)) mouse in which the coding region for a fusion protein of tau and green fluorescent protein replaces the first exon of the Itpr3 gene. We provide immunohistochemical and functional characterization of the cells expressing IP3 receptor type 3 in the olfactory epithelium. These cells bear microvilli at their apex, and we therefore termed them IP3R3 MV cells. The cell body of these IP3R3 MV cells lies in the upper third of the main olfactory epithelium; a long thick basal process projects towards the base of the epithelium without penetrating the basal lamina. Retrograde labeling and unilateral bulbectomy corroborated that these IP3R3 MV cells do not extend axons to the olfactory bulb and therefore are not olfactory sensory neurons. The immunohistochemical features of IP3R3 MV cells varied, suggesting either developmental stages or the existence of subsets of these cells. Thus, for example, subsets of the IP3R3 MV cells make contact with substance P fibers or express the purinergic receptor P2X3. In addition, in recordings of intracellular calcium, these cells respond to ATP and substance P as well as to a variety of odors. The characterization of IP3R3 MV cells as non-neuronal chemoresponsive cells helps to explain the differing descriptions of microvillous cells in the literature.

Tumor Necrosis Factor Alpha Inhibits Olfactory Regeneration in a Transgenic Model of Chronic Rhinosinusitis–Associated Olfactory Loss

Olfactory loss is a debilitating symptom of chronic rhinosinusitis (CRS). Although olfactory sensory neurons (OSNs) are normally regenerated constantly in the olfactory epithelium (OE), a transgenic model of CRS-associated olfactory loss (inducible olfactory inflammation [IOI] mouse) shows that inflammation causes widespread OSN loss without progenitor cell proliferation. In this study, we further examine whether the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) inhibits olfactory regeneration. IOI mice underwent either unilateral bulbectomy or sham surgery and then were induced to express TNF-alpha in the OE for 1 week. After death, the mice were assessed histologically and with bromodeoxyuridine staining to determine the effect of TNF-alpha on olfactory regeneration. In the absence of TNF-alpha, bulbectomy was associated with death of OSNs, followed by robust proliferation of neural progenitors and regrowth of the OE. At 12 days postbulbectomy, OE thickness on the operated side had recovered to >80% of the unoperated side. In mice in which TNF-alpha expression was induced, significantly reduced proliferation was observed, associated with failure of normal reconstitution of OE thickness. The mechanism of olfactory dysfunction in CRS remains incompletely understood. Previous studies with a transgenic mouse model suggested that inflammation inhibits progenitor cell proliferation and olfactory regeneration. Here, the role of the CRS-associated cytokine TNF-alpha was investigated using surgical ablation of the olfactory bulb to stimulate synchronous OSN turnover. We find that TNF-alpha expression prevents normal OE recovery, supporting the role of suppressed olfactory regeneration in the pathophysiology of CRS-associated olfactory loss.

Olfactory glia enhance neonatal axon regeneration

Olfactory ensheathing cells (OECs) migrate with olfactory axons that extend from the nasal epithelium into the olfactory bulb. Unlike other glia, OECs are thought to migrate ahead of growing axons instead of following defined axonal paths. However it remains unknown how the presence of axons and OECs influences the growth and migration of each other during regeneration. We have developed a regeneration model in neonatal mice to examine whether (i) the presence of OECs ahead of olfactory axons affects axonal growth and (ii) the presence of olfactory axons alters the distribution of OECs. We performed unilateral bulbectomy to ablate olfactory axons followed by methimazole administration to further delay neuronal growth. In this model OECs filled the cavity left by the bulbectomy before new axons extended into the cavity. We found that delaying axon growth increased the rate at which OECs filled the cavity. The axons subsequently grew over a significantly larger region and formed more distinct fascicles and glomeruli in comparison with growth in animals that had undergone only bulbectomy. In vitro, we confirmed (i) that olfactory axon growth was more rapid when OECs were more widely distributed than the axons and (ii) that OECs migrated faster in the absence of axons. These results demonstrate that the distribution of OECs can be increased by repressing by growth of olfactory axons and that olfactory axon growth is significantly enhanced if a permissive OEC environment is present prior to axon growth.

Re-evaluation of spontaneous regeneration of the lateral olfactory tract

Spontaneous regeneration of the lateral olfactory tract (LOT) was re-evaluated in newborn rats using a fluorescent retrograde neuronal tracer as objective indicators of complete LOT transection. Complete LOT transection was evidenced by the loss of the white myelinated band characteristic for adult LOT and the total lack of retrograde neuronal labeling of mitral cells by Fast Blue that was injected during LOT transection. In completely LOT-transected young adult rats, mitral cells were retrogradely labeled consistently only by Fluoro-Gold that was injected into the olfactory cortex at the adult stage. Moreover, an anterograde neuronal tracer, biotinylated dextran amine (BDA), was demonstrated to pass from the neonatally LOT-transected bulb, through the transected retrobulbar site, towards the olfactory cortex, far caudally at a level near the optic chiasm. The regenerated structures lacked immunoreactivity for myelin basic protein and electron-dense myelinated axon bundles, and were also characterized by the thinness of the BDA(+) terminal zone within the olfactory cortex and the lack of its caudal extension. Young adult rats subjected to unilateral bulbectomy contralateral to the neonatally LOT-transected side showed perfect ability to discriminate cycloheximide solution by olfaction. From these findings, we conclude that the spontaneously regenerated olfactory system is functional despite structural incompleteness.

The cell surface carbohydrate blood group A regulates the selective fasciculation of regenerating accessory olfactory axons

Cell surface carbohydrates are differentially expressed by discrete subpopulations of primary sensory axons in the mammalian main and accessory olfactory systems. It has been proposed that these carbohydrates provide a glycocode which mediates the sorting of these sensory axons as they project from the olfactory neuroepithelium to their central targets in the main and accessory olfactory bulbs during development. As the differential expression of cell surface carbohydrates on olfactory axons persists in the adult we have now investigated their role during regeneration. We have recently generated a line of transgenic mice, BGAT-Tg, that mis-express the blood group A (BGA) carbohydrate on all primary olfactory axons rather than just on accessory olfactory axons as in wild-type mice. Following unilateral bulbectomy, accessory and main olfactory axons regenerate and grow into the frontal cortex where they fill the cavity which remains after the olfactory bulb ablation. In wild-type mice, the regenerating BGA-expressing accessory olfactory axons selectively aggregated with each other in large bundles but clearly separated from the BGA-negative main olfactory axons. In contrast, in the BGAT-Tg transgenic mice in which all main and accessory axons express the BGA carbohydrate, the accessory olfactory axons failed to correctly separate from the main olfactory axons. Instead, these axons formed numerous small bundles interspersed with main olfactory axons. These data provide strong evidence that the restricted expression of BGA is in part responsible for the selective segregation of accessory olfactory axons.

Investigation of Initial Changes in the Mouse Olfactory Epithelium Following a Single Intravenous Injection of Vincristine Sulphate

To investigate initial changes in the olfactory epithelium, vincristine sulphate (VCR) was administered intravenously once to male BALB/c mice on day 1 in comparison with unilateral bulbectomy (UBT). The light and electron microscopy of the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed sequentially. Further, whole-body radioluminography was conducted at 1 and 24 hours postdose. Apoptosis and an increased number of mitotic cells with a tendency toward decreasing BrdU-positive olfactory epithelial cell counts were observed in olfactory epithelial cells at 6 hours postdose of VCR and became more pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but minimal axonal degeneration was seen in the olfactory nerve from day 4 onward. Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high drug retention even 24 hours after administration. In contrast, UBT showed no effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15. The above results suggest that the initial event of VCR-induced apoptosis in the mouse olfactory epithelium would be mitotic arrest with high drug retention, unlike that evoked by UBT.

Chemosensory Cues are Essential for Mating-Induced Dopamine Release in MPOA of Male Syrian Hamsters

The medial preoptic area (MPOA) is crucial for male sex behavior. Dopamine (DA) is released in MPOA during copulation, and contributes to the reinforcing effects of mating. The aim of the present study was to identify sensory stimuli responsible for mating-induced DA release. Specifically, we determined if chemosensory cues are essential for mating-induced MPOA DA release using in vivo microdialysis in male Syrian hamsters. Hamsters were used because chemosensory cues from the olfactory mucosa and vomeronasal organ are essential for sexual behavior in this species. Sexually experienced adult male hamsters were implanted with a microdialysis guide cannula over MPOA. At the same time, males received sham olfactory bulbectomy (Sham Bx, n = 11), bilateral bulbectomy (Bibx, n = 6), or unilateral bulbectomy (Ubx) ipsilateral (Ipsi Ubx, n = 9) or contralateral (Contra Ubx, n = 8) to the microdialysis probe. This model takes advantage of the predominantly ipsilateral projections of the olfactory bulbs. Microdialysis samples were collected from the MPOA during baseline, exposure to a receptive female, and after removal of female. Extracellular DA was measured using high-performance liquid chromatography with electrochemical detection. During mating, DA increased in MPOA of Sham Bx males (to 146.7 +/- 17.5% of baseline). Bibx males did not mate, and MPOA DA did not increase (96.1 +/- 15.8% of baseline). Although both groups of Ubx males mated to ejaculation, MPOA DA increased significantly only in Contra Ubx males (to 161.8 +/- 35.3% of baseline), and not in males with Ipsi Ubx (107.6 +/- 11.5% of baseline). The results demonstrate that chemosensory cues are essential for MPOA DA release during mating in male Syrian hamsters.

Trans-neuronal regulation of cortical apoptosis in the adult rat olfactory system

Previous work has identified a population of neurons within the anterior piriform cortex that undergo rapid apoptosis following de-afferentation by olfactory bulbectomy in adult rats. The specific initiation signal for apoptosis in this paradigm is unknown, but may include an activity-dependent trans-neuronal cascade. The present report examined the effect of adult-onset unilateral naris occlusion, which reduces olfactory bulb afferent excitation of piriform cortex, on apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) in the rat anterior piriform cortex. Adult Long-Evans hooded rats received unilateral naris occlusion or a control manipulation and were sacrificed after 1, 5, 7, 10 or 20 days later. For comparison, a second group of rats received a unilateral bulbectomy and were sacrificed 24 h later. Counts of TUNEL-stained cell profiles were performed for layers I/II and layer III of the anterior piriform cortex ipsilateral and contralateral to the manipulation. The results confirmed that unilateral bulbectomy produced a dramatic increase in TUNEL labeling in layers I/II of the ipsilateral piriform cortex 24 h after bulbectomy. Unilateral naris closure also produced enhanced TUNEL labeling, although the magnitude of the effect was less than that produced by bulbectomy, and enhanced TUNEL labeling was apparent both ipsilateral and contralateral to the sealed naris compared to controls. Deprivation-induced TUNEL labeling was detectable by 24 h post-closure, peaked at 5 days and was no different from controls by 20 days post-closure. Neither bulbectomy nor naris closure affected TUNEL labeling in layer III. Together, these results suggest that there is a population of superficial cells in piriform cortex whose survival is tightly regulated by sensory input.

Developmental characteristics in adult forebrain following neonatal unilateral olfactory bulbectomy

AbstractIn this study we performed neonatal unilateral olfactory bulbectomy to determine the influence of the olfactory bulb on the development of forebrain anatomical characteristics. Histological examination was used to examine the long‐term effect of the neonatal olfactory bulb removal on the rostral migratory stream general morphology in rats. BrdU‐immunohistochemistry presented here provides evidence of the proliferating cells topography throughout this migratory pathway. To analyse spatial distribution of the rostral migratory stream on bulbectomized versus intact side camera lucida drawing was used. The results show that although the migratory stream anatomical pattern of bulbectomized rats was similar to the control adult ones, an open olfactory ventricle was regularly present within it. These findings indicate that neonatal bulbectomy maintains the prosencephalic region developmental pattern till adulthood.

Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration

Netrin-1 is a bifunctional secreted protein that directs axon extension in various groups of developing axonal tracts. The transmembrane DCC (deleted in colorectal cancer) receptor is described as netrin-1 receptor and is involved in the attractive effects of netrin-1. In this study, we examined the spatio-temporal expression patterns of both netrin-1 and DCC in the rat olfactory system at different stages of development and during axonal regeneration following unilateral bulbectomy. High DCC expression was detected on the pioneer olfactory axons as they are extending toward the telencephalon. This expression was transient since from embryonic day 16 onwards, DCC was no longer detected along the olfactory nerve path. From embryonic day 14 until birth, DCC was also expressed within the mesenchyme surrounding the olfactory epithelium. During the same period, netrin-1 protein was detected along the trajectory of olfactory axons up to the olfactory bulb and its expression pattern in the nasal mesenchyme largely overlapped that of DCC. Moreover, netrin-1 continued to be present during the two first post-natal weeks, and a weak protein expression still persisted in the dorso-medial region of the olfactory epithelium in adult rats. While unilateral bulbectomy induced a transient up-regulation of netrin-1 in the lamina propria, particularly in the dorso-medial region of the neuroepithelium, no DCC expression was detected on the regenerating olfactory axons. In the developing olfactory bulb, the extension of mitral cell axons was associated with DCC presence while netrin-1 was absent along this axonal path. DCC was also highly expressed in the newly formed glomeruli after birth, and a weak DCC expression was still detected in the glomerular layer in adult rats. Taken together, these data support the notion that netrin-1, via DCC expressed on axons, may play a role in promoting outgrowth and/or guidance of pioneering olfactory axons toward the olfactory bulb primordium. Moreover, association of netrin-1 with mesenchymal DCC may provide a permissive environment to the growth of both pioneer and later-growing axons. The maintenance of netrin-1 expression in the nasal mesenchyme of adult rats as well as its regional up-regulation following unilateral bulbectomy infer that netrin-1, even in the absence of DCC, may be involved in the process of axonal growth of newly differentiated olfactory receptor neurons probably through the use of other receptors.

Decline and recovery of olfactory receptor expression following unilateral bulbectomy.

The effects of unilateral olfactory bulb ablation upon the odorant receptor expression were studied during the degeneration/regeneration process in the olfactory epithelium of adult rats. Using the in situ hybridization approach, we compared the time course of decay and recovery of expression for three different receptor subtypes (OR14, OR5, OR124). The number of neurons expressing receptor subtypes dramatically decreased in the olfactory epithelium on the lesioned side and reached a minimum at day 5 postsurgery. A progressive recovery was then observed from day 5 to day 15 postlesion, when a plateau was reached. Noticeable differences in the recovery level of receptor expression were observed according to the zonal patterning: the recovery level for neurons located in the lateral zone reached 70% of the control side value while the recovery levels in the dorsal and medial zones represented 35% and 53% of this value, respectively. Axotomy experiments suggest that zone-specific differences in receptor reexpression reported after bulbectomy might be related to the trophic influence of the olfactory bulb.

Alterations in the neurotrophic factors BDNF, GDNF and CNTF in the regenerating olfactory system.

Neurogenesis, axonal outgrowth and synapse formation are usually restricted to specific stages during central nervous system development, but the mature olfactory system maintains these capacities. The cycle of neuronal turnover can be experimentally induced by surgical ablation of the olfactory bulb (OB). We are interested in the growth factor regulation of these processes and the trophic role played by the target tissue, the OB. We studied the immunohistochemical expression of three neurotrophic factors, brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the rat olfactory neuroepithelium (ON) and OB and in target-deprived ON at 1, 3 and 12 weeks post unilateral bulbectomy. We found BDNF immunoreactivity (IR) was restricted to the basal cells and did not alter postbulbectomy. GDNF-IR was expressed by mature olfactory receptor neurons (ORNs), their axons and target cells in the OB in controls, but was absent from the ON postbulbectomy. Hence, the expression of GDNF by ORNs was found to be target-dependent. CNTF-IR was present in ORNs and their target cells in the OB, in basal cells and in some immature ORNs. Postbulbectomy, CNTF-IR was unaltered in the basal cells, and very low levels were detectable in maturing ORNs in the ON. Our results indicate that these three factors may contribute to the trophic regulation of this neuronal pathway in a coordinated fashion. Previous work has shown that BDNF promotes survival of ORNs in vitro, and TrkB expression has been found in both immature and mature ORNs. Hence, BDNF produced by basal cells may be acting locally on neurons expressing TrkB. Expression of CNTF by both the basal cells and the ORNs suggests that it may play an integral role in this neuronal differentiation pathway. Finally, the expression of GDNF exclusively by mature ORNs in the ON, its presence in the target cells in the OB and abolition of expression by bulbectomy, suggests that it may be target-derived. This provides a major mechanism by which the bulb could exert trophic influences on ORNs.

Upregulation of neural growth-associated protein and neural cell adhesion molecule in mouse olfactory epithelium and axons after unilateral removal of the olfactory bulb.

The expression of synaptosomal-associated protein (SNAP-25), neural growth-associated protein (GAP-43) and neural cell adhesion molecule (NCAM) were studied in mouse olfactory cells and axons for 2 weeks following unilateral bulbectomy. The olfactory cells and axons in the control olfactory epithelium were positive for SNAP-25 but levels decreased in the atrophic olfactory epithelium 3 days after bulbectomy. There was no expression of SNAP-25 in the olfactory epithelium on the bulbectomy side 7 days after bulbectomy, indicating that this protein may be a good marker for the degeneration of olfactory cells. The expression of NCAM was still found in the atrophic olfactory epithelium at 7 days after bulbectomy, while the expression of NCAM in the olfactory epithelium of the bulbectomy side was stronger than that on the control side at 14 days after bulbectomy. The expression of GAP-43 in the olfactory axonal bundles of the bulbectomy side at 3 and 4 days after bulbectomy was stronger than that on the control side. These results suggest that upregulation of NCAM may be related to the regeneration of the olfactory cells, with upregulation of GAP-43 probably playing a role in axonal regeneration after bulbectomy.

Expression of the low affinity neurotrophin receptor, P75NGFR, in the rat forebrain, following unilateral bulbectomy

It has been hypothesized that the main olfactory bulb, with its relatively rich source of neurotrophins, may provide trophic support for neurons that project to the bulb. We monitored expression of the common, low affinity receptor for neurotrophins, p75NGFR, in the olfactory bulb and basal forebrain of unilaterally bulbectomized and sham-treated rats, 1–16 weeks post-surgery, using the monoclonal antibody MAb192. An induction of p75NGFR-immunoreactivity was observed in both the glomerular and olfactory nerve layers of the right, contralateral main olfactory bulb of lesioned animals. The naturally occurring regeneration taking place in the olfactory neuroepithelium is known to be altered by olfactory bulbectomy, with subsequent changes in the sensory input to the remaining bulb. These changes in expression of p75NGFR in the olfactory bulb support the hypothesis we have developed in previous papers, that changes in the extent of the peripheral input from the olfactory neuroepithelium to the main olfactory bulb regulate p75NGFR expression in both the glomerular and the olfactory nerve layers. Expression of p75NGFR in the basal forebrain of bulbectomized animals was found to be no different than sham-treated controls and does not support the hypothesis that the olfactory bulb provides trophic support to this region of the central nervous system.

Bulbectomy of neonatal mice induces migration of basal cells from the olfactory epithelium

Bulbectomy of neonatal mice induced cell migration from the olfactory epithelium in the nasal septum. We examined cell types of migrating clusters by immunohistochemistry using anti-keratin and anti-BrdU antibodies, and by electron microscopy. At 1–2 days after unilateral bulbectomy of P1 mice, cells migrated from the olfactory epithelium to the lamina propria of the septal olfactory mucosa. Horizontal basal cells that reacted specifically with anti-keratin antibody, and globose basal cells characterized by a round shape and poor content of organellae in their cytoplasm, were contained in the cluster. At 1 week, migrated clusters that contained keratin-positive horizontal basal cells were observed in both the lamina propria and olfactory bulb on the unoperated side. At 1 month, not only basal cells but also olfactory cells and presumed supporting cells were involved in the clusters in the lamina propria and olfactory bulb, suggesting that migrated cells do not transform to other phenotypes.

Short-Term Odor Memory: Effects of Posterior Transection of the Lateral Olfactory Tract in the Rat

Thanos, P. K., B. M. Slotnick. Short-Term Odor Memory: Effects of Posterior Transection of the Lateral Olfactory Tract in the Rat. Physiol Behav 61(6) 903–906, 1997.—Rats were trained on a series of novel 2-odor discrimination problems before and after combined unilateral bulbectomy and posterior transection of the contralateral lateral olfactory tract. In postoperative tests, experimental rats performed as well as controls when a short intertrial interval (30 seconds) was used but, in contrast to controls, failed to learn a 2-odor discrimination when the intertrial interval was 10 minutes. When tested on a reversal task, controls showed memory for original learning by making many errors while experimental rats quickly acquired the task. The results suggest that lateral olfactory tract afferents to posterior olfactory cortex may play a significant role in short-term memory for odors.