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The myelin-associated inhibitory proteins (Nogo-A, MAG and OMgp) that prevent axon regeneration in adult CNS, mediate their effects via a receptor referred as NgR1. Beside their inhibitory role in the adult CNS, Nogo-A and NgR1 might also be functionally involved in the developing nervous system. At the present time, no detailed study is available regarding either the onset of NgR1 expression during development or its spatio-temporal pattern of expression relative to the presence of Nogo-A. Two homologs of NgR1, NgR2 and NgR3, have been recently identified, but their function in the nervous system is still unknown in adult as well as during development. We have examined the spatio-temporal expression pattern of both NgR1, NgR2 and NgR3 mRNAs and corresponding proteins in the developing rat olfactory system using in situ hybridization and immunohistochemistry. From E15-E16 onwards, NgR1 mRNA was expressed by differentiating neurons in both the olfactory epithelium and the olfactory bulb. At all developmental stages, including adult animals, NgR1 protein was preferentially targeted to olfactory axons emerging from the olfactory epithelium. Using double-immunostainings in the postnatal olfactory mucosa, we confirm the neuronal localization of NgR1 and its preferential distribution along the olfactory axons. The NgR2 and NgR3 transcripts and their proteins display similar expression profiles in the olfactory system. Together, our data suggest that, in non-pathological conditions, NgR1 and its homologs may play a role in axon outgrowth in the rat olfactory system and may be relevant for the confinement of neural projections within the developing olfactory bulb.

Commonly used experimental paradigms of environmental enrichment combine increased social interactions and sensory inputs and renewal of the objects present in the environment. However, the specific contribution of novelty to the effects of enrichment is unclear. Here, we show that repeated daily exposure to single novel odorants and not to an enriched but stable olfactory environment improves short-term olfactory memory and neurogenesis in the mouse olfactory bulb. In addition, these positive effects are mediated by noradrenalin as they are blocked by a noradrenergic receptor antagonist. These data suggest that novelty recognition and noradrenergic mechanisms are crucial in mediating neural plasticity induced by olfactory enrichment.

The present study examined the influence of pharmacological modulations of the locus coeruleus noradrenergic system on odor recognition in the mouse. Mice exposed to a nonrewarded olfactory stimulation (training) were able to memorize this odor and to discriminate it from a new odor in a recall test performed 15 min later. At longer delays (30 or 60 min), the familiar odor was no longer retained, and both stimuli were perceived as new ones. Following a post-training injection of the α2-adrenoceptor antagonist dexefaroxan, the familiar odor was still remembered 30 min after training. In contrast, both the α2-adrenoceptor agonist UK 14304 and the noradrenergic neurotoxin DSP-4 prevented the recognition of the familiar odor 15 min after the first exposure. Noradrenaline release in the olfactory bulb, assessed by measurement of the extracellular noradrenaline metabolite normetanephrine, was increased by 62% following dexefaroxan injection, and was decreased by 38%–44% after treatment with UK 14304 and DSP-4. Performance of mice in the recall test was reduced by a post-training injection of the β-adrenoceptor antagonist propranolol or the α1-antagonist prazosin, thus implicating a role for β- and α1-adrenoceptors in the facilitating effects of noradrenaline on short-term olfactory recognition in this model.

Neuroblasts born in the subventricular zone (SVZ) migrate along the rostral migratory stream, reaching the olfactory bulb (OB) where they differentiate into local interneurons. Several extracellular factors have been suggested to control specific steps of this process. The brain-derived neurotrophic factor (BDNF) has been demonstrated to promote morphological differentiation and survival of OB interneurons. Here we show that BDNF and its receptor TrkB are expressed in vivo throughout the migratory pathway, implying that BDNF might also mediate migratory signals. By using in vitro models we demonstrate that BDNF promotes migration of SVZ neuroblasts, acting both as inducer and attractant through TrkB activation. We show that BDNF induces cAMP response element-binding protein (CREB) activation in migrating neuroblasts via phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAP-K) signalling. Pharmacological blockade of these pathways on SVZ explants significantly reduces CREB activation and impairs neuronal migration. This study identifies a function of BDNF in the SVZ system, which involves multiple protein kinase pathways leading to neuroblast migration.

In the main olfactory bulb, stimuli are coded within the spatio-temporal pattern of mitral cells' activity. Granule cells are interneurons that shape the mitral cells' activity, and are continuously generated in the adult main olfactory bulb. However, the role of granule cell renewal remains elusive. We show here that an associative olfactory discrimination task reduces the survival of newborn neurons. However, when the olfactory task involves perceptually related odorants, the learning process is slower and does not induce such a reduction in the number of new neurons. Mapping newborn cells within the granule cell layer of the main olfactory bulb reveals a clustered distribution that evolves with learning as a function of odorant similarity and partly overlaps with the immediate-early gene Zif268 expression pattern. These data provide insight into the functional mechanisms underlying olfactory discrimination learning, and promote the importance of neurogenesis as a cellular basis for the restructuring of odor images in the main olfactory bulb.

The adult subventricular zone produces neuroblasts that migrate to the main olfactory bulb, where they differentiate into interneurons in the glomerular and granular layers. Using bromodeoxyuridine labeling, the survival of newborn cells was assessed in these two layers of the MOB in control mice and in mice unilaterally deprived from sensory input by naris occlusion. In control main olfactory bulbs, bromodeoxyuridine-positive cell density decreased about 70% between 15 and 180 days post-bromodeoxyuridine administration but earlier in the glomerular layer than in the granular layer. At all time points examined, newborn cell density was higher in the deep granular layer than in the superficial granular layer. Occlusion started at the age of 2 months and lasted for 15, 30, 45, 60 or 180 days. The newborn cell survival was similarly reduced in both layers by occlusion, during a critical period 15 and 45 days post-occlusion. Interestingly, olfactory deprivation decreased bromodeoxyuridine-positive cell density in the deep granular layer only, indicating a greater dependence of cell fate on sensory input in this sub-layer. Neuronal differentiation was assessed in the granular layer and glomerular layer by multiple double-labeling 45 days post-bromodeoxyuridine-injections, the time point at which the proportion of bromodeoxyuridine-positive cells expressing a neuronal marker reached approximately 85% in the granular layer and approximately 50% in the glomerular layer. Naris occlusion did not significantly affect these proportions. Taken together, our results reveal that the survival of newborn cells has a different time course in the glomerular layer and in the granular layer, but is similarly decreased in each layer by olfactory deprivation. In addition, our data suggest a functional heterogeneity of neurogenesis within the granular layer.

The major impediments to axonal regeneration in the central nervous system are growth-inhibitory proteins present in the myelin sheath, and Nogo-A is one of the most potent inhibitors synthesized by oligodendrocytes. However, neuronal expression of Nogo-A during development suggests that it may have an additional role. The spatio-temporal regulation of both Nogo-A mRNA and protein expression was examined by in situ hybridization and immunohistochemistry in the developing rat olfactory system. During embryonic and postnatal development (from E13 to P6), Nogo-A mRNA and protein were strongly expressed by differentiating neurons in the olfactory epithelium and in the olfactory bulb. From the second postnatal week, a progressive down-regulation of both Nogo-A mRNA and protein occurred, such that only a weak expression persisted in the adult olfactory system. Using double-immunostainings in the adult olfactory epithelium, we determined that Nogo-A was preferentially expressed by immature olfactory receptor neurons extending axonal processes toward the olfactory bulb. At all developmental stages, Nogo-A protein was preferentially targeted in olfactory axons emerging from the olfactory epithelium. Using an in vitro model of olfactory axon growth, we demonstrated that, in addition to its presence along the entire axon length, Nogo-A accumulated in axonal growth cone and at axonal branching points, with a distribution similar to that of microtubule-associated proteins. Moreover, Nogo-A was transiently expressed in dendritic processes in the postnatal olfactory bulb. Together, our data suggest that, in non-pathological conditions, Nogo-A may be involved in the processes of axonal growth and dendritic modeling through the regulation of microtubule dynamics.

Collapsin-response mediator proteins (CRMPs) are highly expressed in the developing brain where they take part in several aspects of neuronal differentiation. CRMPs are still present postnatally, but their function remains speculative in the adult brain. We studied the expression and localization of CRMP1, CRMP2 and CRMP5 in two areas of the nervous system with persistent neurogenesis in adult mice, the olfactory mucosa and the olfactory bulb. In the olfactory mucosa, we have established that CRMP expression is restricted to postmitotic cells of the olfactory neurons lineage. CRMP5 is coexpressed with growth associated protein of 43 kDa (GAP43) in immature olfactory neurons and is down-regulated in olfactory marker protein-positive mature neurons. In contrast, CRMP1 and CRMP2 persist at all stages of differentiation from immature GAP43-positive to fully mature olfactory neurons. In the olfactory bulb, CRMP1, CRMP2 and CRMP5 are abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons. In both areas, the subcellular distribution of CRMP1 or CRMP2 is different in mature vs. immature neurons, suggesting that these proteins are sequentially involved in various cellular events during neuronal lifetime. The variations of CRMP expression following axotomy are consistent with their differential localization and functional involvement in immature vs. mature neurons of the olfactory system. Our data bring new insight to the putative functions of CRMPs within areas of the adult nervous system with permanent neurogenesis, some related to differentiation of newly generated neurons but others occurring in mature neurons with a limited lifespan.

A dysfunction of noradrenergic mechanisms originating in the locus coeruleus has been hypothesised to be the critical factor underlying the evolution of central neurodegenerative diseases [Colpaert FC (1994) Noradrenergic mechanism Parkinson's disease: a theory. In: Noradrenergic mechanisms in Parkinson's disease (Briley M, Marien M, eds) pp 225-254. Boca Raton, FL, USA: CRC Press Inc.]. alpha(2)-Adrenoceptor antagonists, presumably in part by facilitating central noradrenergic transmission, afford neuroprotection in vivo in models of cerebral ischaemia, excitotoxicity and devascularization-induced neurodegeneration. The present study utilised the rat olfactory bulb as a model system for examining the effects of the selective alpha(2)-adrenoceptor antagonist dexefaroxan upon determinants of neurogenesis (proliferation, survival and death) in the adult brain in vivo. Cell proliferation (5-bromo-2'-deoxyuridine labelling) and cell death associated with DNA fragmentation (terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling assay) were quantified following a 7-day treatment with either vehicle or dexefaroxan (0.63 mg/kg i.p., three times daily), followed by a 3-day washout period. The number of terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling-positive nuclei in the olfactory bulb was lower in dexefaroxan-treated rats, this difference being greatest and significant in the subependymal layer (-52%). In contrast, 5-bromo-2'-deoxyuridine-immunoreactive nuclei were more numerous (+68%) in the bulbs of dexefaroxan-treated rats whilst no differences were detected in the proliferating region of the subventricular zone. Terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling combination with glial fibrillary acidic protein or neuronal-specific antigen immunohistochemistry revealed that terminal dideoxynucleotidyl transferase-catalysed 2'-deoxyuridine-5'-triphosphate nick end-labelling-positive nuclei were associated primarily with a neuronal cell phenotype. These findings suggest that dexefaroxan increases neuron survival in the olfactory bulb of the adult rat in vivo, putatively as a result of reducing the apoptotic fate of telencephalic stem cell progenies.

The rat olfactory bulb is innervated by basal forebrain cholinergic neurons and is endowed with both nicotinic and muscarinic receptors. The development of this centrifugal cholinergic innervation occurs mainly in early postnatal stages. This developmental time-course and the demonstration that acetylcholine can modulate some aspects of neuronal proliferation, differentiation or death, suggests the possible involvement of cholinergic afferents in the morphogenesis and/or plasticity of the olfactory bulb. The purpose of the present work was to assess whether acetylcholine could modulate neuronal morphogenesis in the olfactory bulb. Toward this aim, we developed a primary culture model of rat olfactory bulbs. Three major cell types were identified on the basis of their morphological and immunocytochemical phenotype: neuronal-shaped cells expressing the neuronal markers neuron specific enolase, microtubule associated protein 2, neural cell adhesion molecule and beta-tubulin III; glial-like cells immunoreactive for glial fibrillary acidic protein and flattened cells immunolabelled with antibodies against beta-tubulin III and nestin, most likely neuronal precursors. After three to six days of treatment with 100-microM carbachol, a cholinergic agonist, significant increase in neuritic length was observed in cultured olfactory bulb neurons. The neurite outgrowth effect of carbachol was abolished by co-treatment with 1 microM alpha-bungarotoxin, an alpha 7 subunit nicotinic receptor antagonist, but was not affected by the addition of 10 microM atropine, a general muscarinic antagonist. The effect of carbachol was also mimicked by the nicotinic agonists, nicotine (100 microM) and epibatidine (10 microM). This pharmacological profile suggested the involvement of nicotinic receptors of the alpha 7-like subtype as confirmed using 125I-alpha-bungarotoxin receptor autoradiography.Taken together, these data argue for a role for nicotinic receptors in neuritic outgrowth in the rat olfactory bulb and provide a cellular support to the previously described effects of acetylcholine on olfactory bulb plasticity in vivo.

Topographically localized over-expression of the human Bcl-2 protein in retinal glial Müller cells of a transgenic mice (line 71) leads to early postnatal apoptotic Müller cell death and retinal degeneration. Morphological, immunohistological and confocal laser microscopic examination of transgenic and wild-type retinas were achieved on paraffin retinal sections, postnatally. Apoptosis occurs two to three days earlier in the internal nuclear layer of transgenic retinae, than in wild-type littermates. In parallel there was a progressive disappearance of transgenic Hu-Bcl-2 over-expression, as well as of the Müller cell markers, cellular retinaldehyde-binding protein and glutamine synthetase. This phenomenon led to retinal dysplasia, photoreceptor apoptosis and then retinal degeneration and proliferation of the retinal pigment epithelium. The optic nerve, however, remains intact. Two complementary observations confirm the pro-apoptotic action of Bcl-2 over-expression in Müller cells: (i) in the peri-papillary and peripheral regions where the transgene Bcl-2 is not expressed, cellular retinaldehyde-binding protein or glutamine synthetase immunostaining persist and Müller glia do not die; and (ii) the retina conserves a normal organisation in these two regions in spite of total retinal degeneration elsewhere. We conclude that retinal dysplasia and degeneration are linked to primary Müller cell disruption. Besides its generally accepted anti-apoptotic function, over-expression of Bcl-2 also exerts a pro-apoptotic action, at least in immature Müller glia. One may suppose that Bcl-2 translocation resulting in its over-expression in retinal Müller cells could be a putative mechanism for early retinal degeneration.

The small stress protein Hsp27 is expressed during mammalian neural development. We have analyzed the role of this protein in immortalized rat olfactory neuroblasts. In the presence of dopamine a fraction of these cells differentiate into neurons while the remaining cells undergo apoptosis. We report here that the dopamine induced differentiation and apoptosis are associated with a transient and specific accumulation of Hsp27. Moreover, transfection experiments have shown that Hsp27 overexpression drastically decreases the fraction of cells undergoing apoptosis. In contrast, reduction of the endogenous level of Hsp27 led to abortion of differentiation and, therefore, drastically increased the number of apoptotic cells. Furthermore, in the normal cell population we show that Hsp27 accumulation takes place only in differentiating cells that were not undergoing apoptosis. We therefore conclude that Hsp27 may represent a key protein that controls the decision of olfactory precursor cells to undergo either differentiation or cell death.

Dopamine binding sites of D 1 and D 2 /D 3 subtypes had been detected in the rat peripheral olfactory system and postulated to account for dopamine-dependent enhancement of olfactory memory and retro-inhibition of olfactory input within the olfactory bulb, respectively. We further assessed, in the present study, the mechanisms of these dopamine actions by using adenylyl cyclase activity assay and [ 35 S]GTP radioautography in rat olfactory bulb and mucosa. The D 1 agonist SKF 38393 increased adenylyl cyclase activity on membranes of the olfactory bulb, but not on those of the olfactory mucosa. Stimulation of adenylyl cyclase by SKF 38393 in the olfactory bulb was dose dependent, with a half-maximal effect ( ec 50 ) at 0.16 μ M SKF 38393, reaching 40% over basal adenylyl cyclase activity, and was blocked by the D 1 antagonist SCH 23390. The D 2 agonists bromocriptine and quinpirole inhibited both basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. These adenylyl cyclase inhibitions were dose dependent, with ec 50 values of 0.1–0.3 μ M for bromocriptine and 1–3 μ M for quinpirole, equal to 25% of basal enzyme activity at concentrations of 1–10 μ M, and were blocked by the D 2 antagonist eticlopride. The D 2 antagonist was devoid of any effect on basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. Odorant-induced stimulation of adenylyl cyclase was blocked by D 2 agonist in olfactory mucosa membranes, which suggests dopaminergic regulation of odor detection in the olfactory mucosa. By using microdissected fractions of the olfactory mucosa, D 2 agonist-induced inhibition of adenylyl cyclase was shown to occur only in lamina propria, thus co-localizing with D 2 binding sites. [ 35 S]GTP radioautography on tissue sections revealed D 2 agonist-induced G-protein activation in olfactory nerve and glomerular layers of the olfactory bulb, and in the chorion of the olfactory mucosa. Taken together, these data demonstrate functional coupling of the dopamine receptors with adenylyl cyclase in both the olfactory bulb and mucosa, and document novel aspects of dopamine's physiological involvement in olfaction and of D 2 -mediated signal transduction.

The olfactory system provides a useful in vivo model for studying neuronal apoptosis. The synaptic target deafferentation (olfactory bulb ablation) of the sensory epithelium induces a massive and synchronous wave of retrograde apoptosis in the large population of olfactory sensory neurons. The proto-oncogene bcl-2 is involved in the regulation of cell death and is able to block apoptosis in motoneurones. We demonstrate here that olfactory neurons over-expressing the human Bcl-2 protein in transgenic mice are long-term protected from apoptotic death following ipsilateral olfactory bulbectomy. We kinetically assessed neuronal death 32 h, 50 h and 5 days following unilateral olfactory bulbectomy, in adult C57BL6 (wild-type) and transgenic mice with olfactory neurons over-expressing the Human bcl-2 gene. Using the TUNEL method and morphometric analysis of olfactory epithelium, we confirmed the occurrence of a wave of neuronal death in wild-type mice but failed to detect a significant rate of neuronal apoptosis in the olfactory epithelium of transgenic animals. Apoptotic death of olfactory neurons probably shares common pathways with apoptotic processes occuring in other neuronal types, including motoneurons.

The existence of possible relationships among the developmental profile of various cholinergic markers in the main olfactory bulb (OB) was assessed by using in vitro quantitative autoradiography. Muscarinic receptors were visualized with [3H]pirenzepine (muscarinic M1-like sites) and [3H]AF-DX 384 (muscarinic M2-like sites); nicotinic receptors by using [3H]cytisine (nicotinic 42-like subtype) and [125I] alpha-bungarotoxin (nicotinic 7-like subtype); cholinergic nerve terminals by using [3H]vesamicol (vesicular acetylcholine transport sites) and [3H]hemicholinium-3 (high-affinity choline uptake sites). These various cholinergic markers exhibited their lowest levels at birth and reached adult values by the end of the 4-5 postnatal weeks. However, the density of presynaptic cholinergic markers and nicotinic receptors at postnatal day 2 represented a large proportion of the levels observed in adulthood, and displays a transient overexpression around postnatal day 20. In contrast, the postnatal development of cholinergic muscarinic M1-like and M2-like receptors is apparently regulated independently of the presynaptic cholinergic markers and nicotinic receptors. Two neurochemically and anatomically separate olfactory glomeruli subsets were observed in the posterior OB of the developing rat. These atypical glomeruli expressed large amounts of [3H]vesamicol-and [3H]hemicholinium binding sites without significant amounts of muscarinic M1, M2, or nicotinic alpha 4 beta 2 receptor binding sites. A significant density of [125I] alpha-bungarotoxin binding sites could be detected only at early postnatal ages. A few olfactory glomeruli specifically restricted to the dorsal posterior OB expressed a high density of [3H]cytisine binding sites but lacked significant binding of the two presynaptic cholinergic markers used here, suggesting their noncholinergic but cholinoceptive nature.

Expression of the proto-oncogene c-fos is known to increase in granule cells of the olfactory bulb following a sustained olfactory stimulation. Most granule cells displaying high levels of Fos accumulation are located in the bulbar columns defined by the odour-induced foci of high 2-deoxyglucose glomerular uptake. The present studies were undertaken in order to assess the possible involvement of centrifugal afferents in the modulation of odour-induced patterns of either 2-deoxyglucose accumulation or c-fos expression in the olfactory bulb. A unilateral olfactory peduncle section had no effect on the odour-induced 2-deoxyglucose foci but induced a significant decrease in the number of Fos-containing neurons in odour-selective areas of both olfactory bulbs, ipsilateral and contralateral to the lesion. This suppressive effect was much more pronounced in the side ipsilateral to the peduncle section. It is concluded that c-fos expression induced by a sustained stimulation with propionic acid vapours is not only determined by the olfactory peripheral input but also by afferents of central origin. In order to estimate the contingent involvements of the cholinergic and noradrenergic afferents in this control of c-fos expression, we attempted to mimic the effects of the surgical deafferentation on odour-induced c-fos expression by using a pharmacological approach with selective cholinergic and noradrenergic antagonists. The beta-adrenergic antagonist propanolol induced a suppression of the odour-related patterns of Fos accumulation similar to the one caused by the surgical deafferentation of the olfactory bulb. The muscarinic antagonist scopolamine did not alter c-fos expression in the odour-selective area but increased significantly Fos labelling in the other bulbar aspects. Pharmacological investigations indicate that the noradrenergic and cholinergic centrifugal systems are likely involved in the central modulation of c-fos expression in the OB. The Fos protein could be expressed as an early nuclear signal triggering further long-term modifications of the neuronal phenotype, in certain conditions of sensory stimulation involving the activation of centrifugal systems.

Percu comme une mise en cause de la modernite, l’islam deroute, en particulier ceux d’entre nous qui s’inscrivent dans la tradition intellectuelle et spirituelle judeo-chretienne. Le discours dominant, si pertinent soit-il par ailleurs, traite de la question islamique sans vraiment tenir compte des fondamentaux de cette foi. Simplifie jusqu’a la caricature, quand il n’est pas meprise au nom d’une pretendue ouverture d’esprit, l’aspect doctrinal des religions est aujourd’hui largement ignore. Or c’est la doctrine qui definit l’identite et la vision du monde de chaque croyant. Pour remedier a cette carence qui nous empeche d’avancer, Francois Jourdan analyse ici les postulats essentiels de l’islam et du christianisme dans leur coherence propre. Cette mise a plat a le merite d’ouvrir la porte a la comprehension mutuelle et donc au dialogue. Car pour entendre l’autre, il faut avant tout reconnaitre sa difference. La coexistence pacifique entre les croyances et les religions ne peut se realiser sans une approche ouverte et decomplexee de ce qui les unit, mais aussi et surtout de ce qui les separe. Date de premiere edition : 2008.

The olfactory system provides a useful in vivo model for studying the influence of synaptic targets on the survival of relay neurones. The bipolar sensory neurones located in the olfactory mucosa project synaptically onto the ipsilateral olfactory bulb, and their survival depends on the integrity of this connection. We demonstrate here that the retrograde neuronal degeneration induced by olfactory bulb removal involves apoptosis. As revealed by typical nucleosome-sized fragmentations of the genomic DNA, the apoptosis rate reaches a maximum 32 h after bulbectomy. A transient c-fos mRNA accumulation was detected, peaking 16 h after bulbectomy, suggesting that c-fos is involved in the early steps of programmed cell death.

The Collapsin Response Mediator Proteins (CRMPS) are highly expressed in the developing brain, and in adult brain areas that retain neurogenesis, ie: the olfactory bulb (OB) and the dentate gyrus (DG). During brain development, CRMPs are essentially involved in signaling of axon guidance and neurite outgrowth, but their functions in the adult brain remain largely unknown. CRMP5 has been initially identified as the target of auto-antibodies involved in paraneoplasic neurological diseases and further implicated in a neurite outgrowth inhibition mediated by tubulin binding. Interestingly, CRMP5 is also highly expressed in adult brain neurogenic areas where its functions have not yet been elucidated. Here we observed in both neurogenic areas of the adult mouse brain that CRMP5 was present in proliferating and post-mitotic neuroblasts, while they migrate and differentiate into mature neurons. In CRMP5(-/-) mice, the lack of CRMP5 resulted in a significant increase of proliferation and neurogenesis, but also in an excess of apoptotic death of granule cells in the OB and DG. These findings provide the first evidence that CRMP5 is involved in the generation and survival of newly generated neurons in areas of the adult brain with a high level of activity-dependent neuronal plasticity.

Aging of olfactory function (discrimination and short-term memory) was studied in 2, 10, and 23-month-old mice. We also addressed the issue of the responsiveness of the aging system to olfactory experience-dependent plasticity by submitting mice of different ages to an enrichment paradigm, and assessed neurogenesis in the olfactory bulb and the status of the noradrenergic system, 2 effectors of enrichment. Discrimination ability and its response to enrichment were essentially preserved with aging. In contrast, memory and its improvement by enrichment were altered at 10 and 23 months. Regarding neurogenesis, we found less proliferation of progenitors at 10 months and then lower neuronal differentiation and survival at 23 months. Furthermore, enrichment did not improve neurogenesis beyond the age of 2 months. Noradrenergic markers and their response to enrichment were altered at 23 months in line with memory performance. Aging thus differentially affected olfactory discrimination and memory abilities and their responsiveness to enrichment. Bulbar neurogenesis was an early target of aging whose decline could contribute to age-dependent memory impairments.

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits.

International audience; Regulation of microtubule dynamics is crucial for axon growth and guidance as well as for the establishment of synaptic connections. STOPs (Stable Tubule Only Polypeptides) are microtubule-associated proteins that regulate microtubule stabilization but are also able to interact with actin or Golgi membranes. Here, we have investigated the involvement of STOPs during the development of the olfactory system. We first describe the spatio-temporal expression patterns of N- and E-STOP, the two neuronal-specific isoforms of STOP. E- and N-STOP are expressed in the axonal compartment of olfactory sensory neurons, but are differentially regulated during development. Interestingly, each neuronal isoform displays a specific gradient distribution within the olfactory nerve layer. Then, we have examined the development of the olfactory system in the absence of STOPs. Olfactory axons display a normal outgrowth and targeting in STOP-null mice, but maturation of the synapses in the glomerular neuropil is altered.

Behavioral and physiological evidence indicates that odor processing in the main olfactory bulb is influenced by olfactory experience. At the cellular level, changes in inhibitory influence exerted by granular interneurons may contribute to restructuring odor representations. To assess experience-dependent modulation in the responsiveness of granule cells, we measured the level and spatial distribution of odor-induced expression of the immediate-early gene Zif268 in the granule cell layer of adult mice submitted or not to olfactory discrimination conditioning. We first show that stimulation by the reinforced odorant in conditioned animals did not induce any increase in Zif268 expression in contrast to stimulation with an unfamiliar odorant which induced an odor-specific three-fold increase in Zif268 expression. The same lack of Zif268 induction was observed in animals exposed to odorants without learning, indicating that familiarity to the odorant with or without conditioning similarly reduced responsiveness of granule cells to odorant stimulation. Second, conditioning induced a spatial reorganization of Zif268-positive cells leading to higher contrast and significant enlargement of their distribution pattern. The latter effect was also present in animals exposed to the odorants without conditioning but was significantly weaker. Taken together, these data indicate that distinct populations of granule cells are solicited by odorant processing, depending on its familiarity or behavioral significance. Finally, we report that the expression pattern of Zif268 in the granule cell layer is constrained by anteroposterior and dorsolateral gradients in cell density, pointing to anatomical and possibly functional disparity within the layer.

Olfactory deficiency has been reported in the early stages of Alzheimer's disease (AD) in humans but is very poorly understood due to the lack of investigations in animal models of AD. Recent studies point to the noradrenergic system as an important target of the AD pathological process. In addition, noradrenalin has been shown to influence adult neurogenesis which is implicated in cognitive functions. We have therefore investigated the olfactory neurogenesis and cognitive performances in young transgenic Tg2576 mice in relation with the status of the noradrenergic and the cholinergic systems. Tg2576 showed a deficit in neurogenesis in the olfactory bulb evidenced by an increased death of newborn cells and a reduced expression of PSA-NCAM. The locus coeruleus degenerated in Tg2576 between the age of 6.5 and 8 months. These changes were associated with olfactory memory impairments. Our findings indicate that a noradrenergic deficiency could play a role in the early stages of the pathological process in this transgenic model and induce olfactory cognitive impairments through an alteration of olfactory neurogenesis.

The olfactory bulb is the target of neural progenitor cells that are generated in the subventricular zone of the lateral ventricle in the adult brain. This permanent neurogenesis is likely influenced by olfactory input to the bulb since previous studies have shown that cell proliferation and/or apoptotic death are stimulated by naris closure or surgical transection of the olfactory nerve. Since the olfactory bulb is densely innervated by noradrenergic afferents originating in the locus coeruleus, we have studied the impact of pharmacologically activating this noradrenergic system on cell death and proliferation following unilateral olfactory axotomy in the adult mouse olfactory bulb. We found that noradrenaline release in the olfactory bulb was significantly increased by intraperitoneal injections of the selective alpha(2)-adrenoceptor antagonists, dexefaroxan (0.63 mg/kg) and 5-fluoro-methoxyidazoxan (F 14413; 0.16 mg/kg). A chronic treatment with either compound for 7 days following olfactory axotomy significantly reduced neuronal death, glial activation and cell proliferation in the deafferented olfactory bulb. These data (1) confirm that alpha(2)-adrenoceptor antagonists, presumably by facilitating central noradrenergic transmission, afford neuroprotection in vivo, as previously shown in models of cerebral ischemia, excitotoxicity and devascularization-induced neurodegeneration, and (2) support a role of the locus coeruleus noradrenergic system in promoting survival of neurons in areas of the brain where neurogenesis persists in the adult.

The main olfactory bulb (MOB) is the first relay on the olfactory sensory pathway and the target of the neural progenitor cells generated in the subventricular zone (SVZ) lining the lateral ventricles and which migrate along the rostral extension of the SVZ, also called the rostral migratory stream (RMS). Within the MOB, the neuroblasts differentiate into granular and periglomerular interneurons. A reduction in the number of granule cells during sensory deprivation suggests that neurogenesis may be influenced by afferent activity. Here, we show that unilateral sensory deafferentation of the MOB by axotomy of the olfactory receptor neurons increases apoptotic cell death in the SVZ and along the rostro-caudal extent of the RMS. The vast majority of dying cells in the RMS are migrating neuroblasts as indicated by double Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling/PSA-NCAM labeling. Counting bromodeoxyuridine-labeled cells in animals killed immediately or 4 days after tracer administration showed a bilateral increase in proliferation in the SVZ and RMS which was balanced by cell death on the operated side. These data suggest that olfactory inputs are required for the survival of newborn neural progenitors. The greatest enhancement in proliferation occurred in the extension of the RMS located in the MOB, revealing a population of local precursors mitotically stimulated following axotomy. Together, these findings indicate that olfactory inputs may strongly modulate the balance between neurogenesis and apoptosis in the SVZ and RMS and provide a model for further investigation of the underlying molecular mechanisms of this activity-dependent neuronal plasticity.

The olfactory epithelium of adult mouse, where primary sensory neurons are massively committed to apoptosis by removal of their synaptic target, was used as a model to determine in vivo mechanisms for neuronal cell death induction. A macro-array assay revealed that the death of olfactory neurons is accompanied with over-expression of the serine protease inhibitor Spi2. This over-expression is associated with decreased serine protease activity in the olfactory mucosa. Moreover, in vitro or in vivo inhibition of serine proteases induced apoptotic death of olfactory neuronal cells. Interestingly, Spi2 over-expression is not occurring in olfactory neurons but in cells of the lamina propria, suggesting that Spi2 may act extracellularly as a cell death inducer. In that sense, we present evidence that in vitro Spi2 overexpression generates a secreted signal for olfactory neuron death. Hence, taken together these results document a possible novel mechanism for apoptosis induction that might occur in response to neurodegenerative insults.

The olfactory bulb is a limbic paleocortex which receives monosynaptic sensory afferents from the olfactory mucosa, and a strong direct cholinergic input from the basal forebrain. This review focuses on the rat olfactory bulb as a suitable model to study cholinergic involvements in cortical processing, during development, adulthood and aging. Anatomical and biochemical data show that cholinergic influences upon the bulbar neuronal network are exerted through several types of target cells and receptors (muscarinic and nicotinic). Functional data indicate that cholinergic afferents to the olfactory bulb are involved in local events related to olfactory learning. Neurodegenerative disorders such as Alzheimer's disease involve early olfactory deficits and typical histopathological lesions in the olfactory bulb. In summary, with its exclusively extrinsic cholinergic innervation and direct sensory input, the rat olfactory bulb offers the opportunity to study the cellular and molecular mechanisms of cholinergic influences on cortical processing, in both normal and pathological conditions.

Olfactory bulb (OB) of mammals contains a large population of dopaminergic interneurons within the glomerular layer. Dopamine has been shown in vivo to modulate several aspects of olfactory information processing. The dopamine receptors of olfactory bulb and mucosa are assessed here at the levels of mRNAs and radioligand binding sites with presently available tools. D1A mRNA was found in OB glomerular-, plexiform-, mitral-cell and granular layers, but not in olfactory mucosa. D1B mRNA was absent in olfactory bulb and mucosa. D1-like binding sites were detected with two distinct radioligands, in glomerular-, plexiform-, mitral cell- and granular layers of OB but not in olfactory mucosa. We thus demonstrate the previously doubtful presence of D1-like receptors in OB. D2 mRNAs were localized in the glomerular and granular layers of OB and in olfactory mucosa; lesser amounts of D3 mRNAs were found in OB glomerular and granular layer, but not in olfactory mucosa. No D4 mRNA was detected in either structure. High densities of D2-like, [125I]Iodosulpride-labelled binding sites, were revealed within lamina propria of olfactory mucosa, and confirmed in the olfactory nerve- and glomerular layers of OB. A faint but significant density of [3H]7-hydroxy-dipropyl-aminotetralin (OH-DPAT) labelled, D3 binding sites was detected in olfactory nerve- and glomerular layers of OB, but not in olfactory mucosa. Competition of [125I]Iodosulpride specific binding by three D2/D3 selective drugs yielded kinetics typical of the D2 receptor subtype in olfactory bulb and mucosa. Olfactory nerve- and glomerular layers of OB are proved thus to contain a predominant contingent of D2 receptors and a minor population of D3 receptors, while olfactory mucosa expresses only D2 receptors.

To provide anatomical information on the complex effects of acetylcholine (ACh) in the olfactory bulb (OB), the distribution of different cholinergic muscarinic and nicotinic receptor sub-types was studied by quantitative in vitro autoradiography. The muscarinic M1-like and M2-like sub-types, as well as the nicotinic bungarotoxin-insensitive (alpha 4 beta 2-like) and bungarotoxin-sensitive (alpha 7-like) receptors were visualized using [3H]pirenzepine, [3H]AF-DX 384, [3H]cytisine and [125I] alpha-bungarotoxin (BTX), respectively. In parallel, labelling patterns of [3H]vesamicol (vesicular acetylcholine transport sites) and [3H]hemicholinium-3 (high-affinity choline uptake sites), two putative markers of cholinergic nerve terminals, were investigated. Specific labelling for each cholinergic radioligand is distributed according to a characteristic laminar and regional pattern within the OB revealing the lack of a clear overlap between cholinergic afferents and receptors. The presynaptic markers, [3H]vesamicol and [3H]hemicholinium-3, demonstrated similar laminar pattern of distribution with two strongly labelled bands corresponding to the glomerular layer and the area around the mitral cell layer. Muscarinic M1-like and M2-like receptor sub-types exhibited unique distribution with their highest levels seen in the external plexiform layer (EPL). Intermediate M1-like and M2-like binding densities were found throughout the deeper bulbar layers. In the glomerular layer, the levels of muscarinic receptor subtypes were low, the level of M2-like sites being higher than M1. Both types of nicotinic receptor sub-types displayed distinct distribution pattern. Whereas [125I] alpha-BTX binding sites were mostly concentrated in the superficial bulbar layers, [3H]cytisine binding was found in the glomerular layers, as well as the mitral cell layer and the underlying laminae. An interesting feature of the present study is the visualization of two distinct cholinoceptive glomerular subsets in the posterior OB. The first one exhibited high levels of both [3H]vesamicol and [3H]hemicholinium-3 sites. It corresponds to the previously identified atypical glomeruli and apparently failed to express any of the cholinergic receptors under study. In contrast, the second subset of glomeruli is not enriched with cholinergic nerve terminal markers but displayed high amounts of [3H]cytisine/nicotinic binding sites. Taken together, these results suggest that although muscarinic receptors have been hypothesized to be mostly involved in cholinergic olfactory processing and short-term memory in the OB, nicotinic receptors, especially of the cytisine/ alpha 4 beta 2 sub-type, may have important roles in mediating olfactory transmission of efferent neurons as well as in a subset of olfactory glomeruli.

Acetylcholinesterase (AChE) histochemistry in light and electron microscopy was used to identify cholinoceptive neurons in the olfactory bulb of adult and 15-day-old rats. Double-labelling experiments using AChE histochemistry and either tyrosine hydroxylase or GABA immunocytochemistry with light microscopy were also performed in order to specify the chemical nature of cholinoceptive neurons. Superficial short-axon cells and several morphological subtypes of deep short-axon cells (second-order interneurons) are the most numerous AChE-containing intrinsic neurons in the olfactory bulb. Short-axon interneurons seem to be the only neurons expressing AChE in the deep olfactory bulb since the numerous granule cells (first-order interneurons) were never found to be AChE-positive, even in electron microscopy. In the superficial olfactory bulb, cholinoceptive cells belong to several neuronal categories. In addition to the intensely labelled superficial short-axon cells, a few periglomerular cells (first-order interneurons) display weak but significant AChE expression, clearly visible in electron microscopy. Both ultrastructural and double-labelling observations support the hypothesis that a subset of superficial tufted cells is also cholinoceptive. The coexistence of AChE and tyrosine hydroxylase in large neurons located in the glomerular and superficial external plexiform layers indicates that some, if not all, cholinoceptive tufted cells belong to the dopaminergic population previously observed in this area. These observations indicate that several types of intrinsic neurons express AChE and can be tentatively considered as cholinoceptive. Our results provide an anatomical substrate for hypotheses concerning the complex effects of acetylcholine in the processing of sensory information in the olfactory bulb.

The ultrastructural organization of cholinergic afferents to the rat olfactory bulb (OB) was studied with the aid of choline acetyltransferase (ChAT) immunocytochemistry in electron microscopy. Particular attention has been paid to a subset of glomeruli characterized by a remarkably high density of cholinergic afferents. Numerous cholinergic terminals making symmetric or asymmetric synaptic contacts were observed in the periglomerular area. ChAT-labelled terminals have a diameter ranging from 0.3 to 1.5 micron and contain numerous clear agranular vesicles. Axo-somatic and axo-dendritic contacts were both observed in contact with several types of target neurons. Three types of cholinoceptive, noncholinergic neurons could be identified: periglomerular cells, superficial short-axon cells, and external tufted cells. Our results provide an anatomical substrate for the hypotheses concerning the complex effects of acetylcholine in the processing of sensory information in the olfactory bulb.

The olfactory bulb of adult male rats stimulated with propionic acid vapours displays a characteristic focus of high metabolic activity in the dorso-medial glomeruli, as revealed by the 2-deoxyglucose (2DG) method. Injection of the dopaminergic agonist apomorphine (1.5 mg kg-1) prior to odour stimulation completely abolishes this selective pattern of glomerular activation, while the metabolic activity of other bulbar areas is not significantly altered. This effect is abolished by a previous injection of the dopamine antagonist haloperidol (0.1 mg kg-1). These observations emphasize the probable involvement of dopamine and dopamine receptors in the bulbar processing of olfactory information.

The present study has defined the developmental time course and the distribution patterns of neuronal fibers and cell bodies displaying acetylcholinesterase (AChE) activity or choline acetyltransferase (ChAT) immunoreactivity in the rat olfactory bulb. The results indicate that the deployment of centrifugal AChE-containing fibers is essentially postnatal. The subset of atypical glomeruli, including the modified glomerular complex, is innervated as early as the first postnatal day while the normal ones are not reached by this type of afferent before postnatal day 6. The comparison of AChE labelling with ChAT immunoreactivity strongly supports the assumption that AChE-containing fibers represent mainly, if not exclusively, the cholinergic bulbopetal innervation emanating from the basal forebrain. A quantitative study has confirmed that the density of labelled fibers increases gradually in the postnatal period and spreads heterogeneously among the bulbar layers. The selective precocious innervation of atypical glomeruli is in favor of their involvement in the early processing of olfactory information in the olfactory bulb. Acetylcholinesterase is also expressed within a subset of ChAT-negative interneurons of the developing olfactory bulb. The number of neurons expressing AChE increases from birth to postnatal day 15 and then decreases to reach the adult value on about postnatal day 30. This neuronal population could constitute a cholinoceptive subset mediating the effects of cholinergic afferents on the bulbar neuronal network.

Numerous anatomical and electrophysiological studies have demonstrated a lack of simple point-to-point topographical relationships between the olfactory bulb and primary olfactory projection areas. They reveal instead, a complex pattern of divergence and convergence. Furthermore, several authors reported that a single mitral cell could project onto different widely spaced cortical regions of the olfactory cortex. In the present study, we attempted to label the projections of a few mitral cells so close together so that they might be assumed to be connected to the same glomerulus, and to determine if these cells had similar patterns of axonal projections. For this purpose small Phaseolus vulgaris leucoagglutinin (PHA-L) injections were performed in the olfactory bulb of adult rats. We found that labelling two to five mitral cells, lying close together in the mitral cell layer, resulted in well-delineated patches of labelled fibres in the cortex. The number of patches was not related to the number of labelled mitral cells but the fibre density in each patch increased with the number of PHA-L filled somata in the olfactory bulb. We conclude that mitral cells lying close together in the mitral cell layer have similar patterns of axonal projections. Functional implications of such an organization in olfactory coding is discussed.

La presence en France de populations issues de cultures tres differentes de la notre se traduit pour les medecins en general et les hospitaliers en particulier par la confrontation au comportement inattendu voire parfois agressif de certains patients. La connaissance de la conception du corps dans la sphere musulmane ne resout pas magiquement les problemes ainsi generes mais peut contribuer a les situer pour mieux les aborder.

The uptake of 14C deoxyglucose (2DG) has been studied in various hypothalamic and limbic structures of male rats exposed to female odors. Uptake differences were visualized by image processing and quantified by measurement of optical density ratios. With respect to the control group, an increase in uptake was observed in the lateral hypothalamic area (LHA), not only in the olfactory bundle, but also, and more obviously, in the parafornical part. This 2DG response is not a result of an odor-induced general motor activation, although it seems to depend on the behavioral reaction of the animal towards the odor. A similar correspondence was not observed for the 2DG response to odor in the ventromedial hypothalamus. Observations in the medial preoptic area, in the corticomedial amygdala, in the lateral septum, or in the dorsomedial hypothalamus did not reveal any significant change in 2DG uptake.

The labelling of olfactory bulb glomeruli following horseradish peroxidase lavage of the nasal cavity has been studied in the rat. In such conditions, atypical glomeruli, previously described according to their high acetylcholinesterase content, display a strong tracer accumulation. The course of afferent olfactory fibres could be followed along the lateral and dorsal surface of the olfactory bulbs. The primary olfactory axons ending in atypical glomeruli have been identified with horseradish peroxidase in electron microscopy. They differ significantly from classical olfactory terminals owing to the presence of large dense-cored vesicles accompanying small clear ones. Moreover, the olfactory terminals do not gather in dark nodules as they do classically in olfactory glomeruli. The study demonstrates that a subset of olfactory neuroreceptors displaying original ultrastructural characteristics projects selectively into atypical olfactory glomeruli. Ultrastructural features indicate that olfactory information processing taking place in the neuropil might be similar to that which occurs in typical glomeruli. Considered together, the atypical olfactory neuroreceptors, glomeruli and acetylcholinesterase-containing centrifugal fibres could constitute a new olfactory subsystem. This hypothesis is discussed by taking into account previous demonstration of other olfactory subsystems devoted to the processing of olfactory cues of fundamental biological importance.

We have developed a computer-assisted method for analyzing the 2-deoxyglucose (2-DG) autoradiograms of mice olfactory bulbs. The purpose of the study was to numerize the maps of glomerular activation in order to achieve a statistical comparison of the glomerular patterns evoked by different stimuli. The spatial distribution of glomerular activation was displayed on unfolded representations of the glomerular layer which were built up using glomerular optical densities (OD) measured systematically within 13 sections per bulb. Each bulbar sample was converted into an 'OD profile'. A matrix composed of 18 OD profiles was submitted to a principal component analysis. The first factor which accounted for 28% of the variance separated unambiguously two clusters corresponding to the bulbs issued from animals stimulated with amylacetate and isovaleric acid, respectively. The second and third factors which accounted for 14% and 12% of the variance segregated the control group (animals exposed to pure air) from the odor-stimulated ones. It was demonstrated that the cluster separation was actually due to the specific spatial distribution of the most-labelled glomeruli. A particular attention was paid to the well-delineated glomerular activation evoked by isovaleric acid. The results demonstrate the specificity and reliability of the glomerular 2-DG patterns. The method should be useful for further comparisons of patterns elicited by larger sets of odorant compounds.

The olfactory organ of tench is functionally divided in a vestibule and a gallery. Experimental observations are presented indicating that an unidirectional watercurrent is created from the vestibule to the gallery via the corridors which are formed by the leaves of the olfactory rosette. The conditions for creating the watercurrents are: oriented and symmetrical beats of cilia situated on the walls of the corridors, and appropriate spacing of the corridors. This principle for water sampling is found in the olfactory organs of trout, carp, roach, catfish, eel, rockling and dogfish. In some other fishes studied the olfactory organs have accessory olfactory sacs and there is no subdivision in vestibule and gallery. In these organs the watercurrents are achieved by a pumping mechanism of the sacs.

The intracranial course of the terminal nerve was studied in the sheep. Luteinizing hormone-releasing hormone (LHRH) immunohistochemistry and acetylcholinesterase (AChE) activity detected histochemically revealed the existence of a major bundle of neural fibers coursing along the anterior cerebral artery, from the olfactory tubercle to the olfactory bulbs, at the surface of which the fibers spread out in a dense plexus, before reaching the cribiform plate. There were ganglia along the nerve, which contained at least two separate populations of identified cells: one possessing AChE activity and the other presenting LHRH immunoreactivity.

Current models of sensory coding in the olfactory bulb are based on the notion of topographical specificity in the processing of stimuli. Part of this hypothesis comes from studies of patterns of radiolabelled 2-deoxyglucose uptake, and local morphometric variations of the mitral cell size observed following prolonged exposure to an odor. The present study explored the possibility that exposing young rats to a long-term stimulation with an odor would induce spatially distributed volumetric variations of the bulbar layers. Three groups of 5 rats have been studied: (1) stimulated with ethyl acetoacetate from birth to 1 month of age, (2) unilaterally deprived following early cauterization of one nostril, and (3) normal animals of same age. Fourteen frontal histological sections uniformly distributed along the rostrocaudal axis of the olfactory bulb were used for this study. Areas of the bulbar layers were measured with the aid of an image analyser and the volume of the corresponding layers deduced by computation. Following complete sensory deprivation, the volume of all bulbar layers, except the periventricular core, was homogeneously reduced along the rostrocaudal axis of the olfactory bulb. Following long-term stimulation with ethyl acetoacetate, volume reduction was significantly higher in anterior and middle regions than in the posterior part of the olfactory bulb. It is assumed that neuronal pathways activated by ethyl acetoacetate stimulation are mainly located in the posterior part of the olfactory bulb. Functional interpretations of these results are discussed with respect to the spatial dimension in olfactory coding.

International audience; An original pathway of centrifugal acetylcholinesterase-positive fibres is described in the olfactory bulb of the rat. A dense network of positive fibres spreads out superficially at the boundaries of the lateral olfactory tract and the glomerular layer. These labelled fibres converge towards atypical glomerular structures lying close to the classical olfactory glomeruli. The atypical glomeruli are located dorsally at the medial border of the accessory olfactory bulb, in the area previously described as the "modified glomerular complex", and in the ventrolateral bulbar area. They structurally differ from typical glomeruli, as suggested by observations on semithin sections. The ultrastructural distribution of acetylcholinesterases into axonal and dendritic profiles, around and inside atypical glomeruli, is consistent with the hypothesis of centrifugal modulatory influences at this level. This study illustrates several new aspects of morphofunctional heterogeneity in the olfactory system. The glomerular layer of the main olfactory bulb can no longer be considered as morphologically and functionally uniform. Atypical glomeruli located in the mediodorsal and the ventrolateral boundaries of the glomerular layer are characterized by both structural features and an uncommonly high convergence of acetylcholinesterase-positive centrifugal fibres. Such areas might be involved in the processing of specific olfactory signals as demonstrated elsewhere for the "modified glomerular complex".

A morphometric study of the glomerular population in the olfactory bulb of the mouse has been carried out by using stereological methods. On the basis of the assumption that the glomerular population is a polydispersed system of spheres, glomerular profile distributions obtained from profile measurements were subjected to a mathematical unfolding procedure to obtain the actual glomerular size distribution. We used a distribution-free method to account for the combined effects of overprojection due to section thickness and truncation (two missing profile mechanisms). Results proved better than those obtained directly from profile measurements without stereological analysis. Several new findings were obtained. First, significant variations of the glomerulus sizes were found along the rostrocaudal axis. The glomeruli are larger in the middle region of the olfactory bulb, whereas their numerical density decreases in the same region. Moreover, the profile density is homogeneous along the rostrocaudal axis. In other words, the relative surface occupied by the periglomerular cells in the glomerular layer is invariant. As a consequence, it may be concluded that the variations in size and numerical density are inversely correlated. Thus, since the glomeruli are larger in the middle region, their number per unit volume is logically smaller in this same area. Finally, the computerization of all these data has led us to estimate the number of glomeruli (1,810 +/- 41) in the olfactory bulb of the mouse. In order to get a comparative idea of their advantages and disadvantages, other standard stereological methods were used in the present study to determine this number. Functional interpretations of the variations of the size and numerical density along the rostrocaudal axis of the olfactory bulb are discussed with respect to ontogenetic and morphofunctional data obtained elsewhere.

A method has been developed for visualizing the patterns of uptake of radioactive 2-deoxyglucose (2-DG) induced in the glomerular layer of rat olfactory bulbs by various olfactory stimuli. Some characteristics of these patterns such as shape, contrast, symmetry, specificity and variability, are discussed. This method is thought to be useful for understanding olfactory coding at the glomerular level.

Jourdan François. La neurobiologie et ses acteurs : fantasmes, pouvoirs et principes de réalité. In: Raison présente, n°57, 1er trimestre 1981. Le matin des biologistes ? pp. 33-55.

We have studied the patterns of glomerular activation evoked in the olfactory bulbs of C57BL/6J and AKR/J mice by olfactory stimulations with amyl acetate or isovaleric acid. Patterns of glomerular activation were obtained with the 2-deoxyglucose method and subsequently compared using a computer-assisted image analysis. The mice of both inbred strains stimulated with amyl acetate or isovaleric acid were characterized by areas of high 2-deoxyglucose uptake in their glomerular layer. Statistical comparisons of the patterns demonstrated that they were odor-specific. Although C57BL/6J mice have been found to be specifically anosmic to isovaleric acid, our findings indicate that their olfactory system is topographically activated by olfactory stimulations with this odorant. However, patterns of glomerular activity evoked by isovaleric acid stimulations are not similar in the two studied strains.