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PubMed2003

The alteration of odor-induced c-Fos immunoreactivity in the rat olfactory bulb after olfactory nerve transection.

We used the rats in which one olfactory nerve had been transected and observed the odor (Propionic acid) -induced c-Fos immunoreactivity in the bulb at different times (2, 4, 8 weeks) after nerve transection. The exposure to odor produced a strong cluster of c-Fos positive cells in the mediodorsal region of the intact bulb. On the other hand, the transected bulb showed much less reactivity 2 weeks after neurectomy; however, a large number of positive cells were observed in the whole of the bulb from 4 weeks after neurectomy. Furthermore, we measured the levels of mRNA for tyrosine hydroxylase (TH), which was the marker of odor-induced olfactory nerve activity in the bulb, by using real-time PCR. The level of TH mRNA decreased on the transected side at 2 weeks but recovered to the level of the contralateral side at 4 weeks after neurectomy. We firstly demonstrated that projection mapping of odor receptors was altered after olfactory nerve transection by using an immunohistochemical method.

Animals↗
PubMed1996

Recovery of olfactory function in thirteen-day-old rats after olfactory bulb transplantation but not after olfactory bulb ablation.

Previous studies have shown recovery of olfactory ability along with reconnectivity of olfactory nerve (ON) following both olfactory bulb (OB) lesions and OB transplants (TX) when performed in newborn rats. The purpose of the present study is to correlate functional recovery with patterns of anatomical reconnectivity in older, postnatal (PN) 13-day-old rats (a possible critical period for plasticity in the system). Reinnervation of olfactory areas was seen in all OB TX animals regardless of the extent of functional recovery. Eight of nineteen animals with OB TXs demonstrated some degree of behavioral recovery. No reinnervation or behavioral recovery of OB lesion animals was observed. At this age, behavioral recovery is dependent upon reconnectivity within the system and transplantation may be required to facilitate this process.

Age Factors↗
PubMed1998

Changes in neurotransmitter release in the main olfactory bulb following an olfactory conditioning procedure in mice.

Olfactory learning is associated with substantial neural changes at the level of the accessory and main olfactory bulb, during both pheromonal learning in mated mice and lamb odour recognition in post partum sheep. These forms of learning occur during "sensitive periods" and an important question is whether similar neural changes occur in the olfactory bulb at other times. We used a classical conditioning procedure to establish an olfactory discrimination in adult mice and then measured changes in neurotransmitter levels in the main olfactory bulb in response to the presentation of the conditioned odours. Presentation of the conditioned, but not the non-conditioned, odour resulted in significant increases in the levels of certain transmitters, including glutamate from the mitral/tufted cells, GABA from the granule and periglomerular cells and noradrenaline from the centrifugal projection from the locus coeruleus. Overall, there was a decrease in the ratio of excitatory to inhibitory neurotransmitters in the olfactory bulb in response to the conditioned, but not the non-conditioned odour. Moreover, the magnitude of the decrease in this ratio was correlated with the level of behavioural response to the conditioned odour. These findings support the hypothesis that changes in the gain of the reciprocal synapses between mitral/tufted neurons and their inhibitory interneurons are a general feature of olfactory learning.

Animals↗
PubMed2006

Cholinergic modulation in the olfactory bulb influences spontaneous olfactory discrimination in adult rats.

Cholinergic neuromodulation in the olfactory bulb has been hypothesized to regulate mitral cell molecular receptive ranges and the behavioral discrimination of similar odorants. We tested the effects of cholinergic modulation in the olfactory bulb of cannulated rats by bilaterally infusing cholinergic agents into the olfactory bulbs and measuring the rats' performances on separate spontaneous and motivated odor-discrimination tasks. Specifically, 6 microL/bulb infusions of vehicle (0.9% saline), the muscarinic antagonist scopolamine (7.6 mM and 38 mM), the nicotinic antagonist mecamylamine hydrochloride (3.8 mM and 19 mM), a combination of both antagonists, or the acetylcholinesterase inhibitor neostigmine (8.7 mM) were made 20 min prior to testing on an olfactory cross-habituation task or a rewarded, forced-choice odor-discrimination task. Spontaneous discrimination between chemically related odorants was abolished when nicotinic receptors were blocked in the olfactory bulb, and enhanced when the efficacy of cholinergic inputs was increased with neostigmine. Blocking muscarinic receptors reduced but did not abolish odor discrimination. Interestingly, no behavioral effects of modulating either nicotinic or muscarinic receptors were observed when rats were trained on a reward-motivated odor-discrimination task. Computational modeling of glomerular circuitry demonstrates that known nicotinic cholinergic effects on bulbar neurons suffice to explain these results.

Acetylcholine↗
PubMed1991

Calbindin-D-28k-like immunoreactive structures in the olfactory bulb and anterior olfactory nucleus of the human adult: distribution and cell typology--partial complementarity with parvalbumin.

Calbindin-D-28k and parvalbumin are calcium-binding proteins. The laminar distribution and morphological features of calbindin-D-28k-like immunoreactive structures were studied in 60-microns-thick sections of the human olfactory bulb. Except for the olfactory nerve layer, immunoreactive neurons were present in all layers of the olfactory bulb. They reached highest densities in the external plexiform layer and internal granule cell layer. Considerable numbers of calbindin-like nerve cells were also found in the olfactory tract and in distal portions of the anterior olfactory nucleus. When comparing the distribution of calbindin-positive structures to that of parvalbumin-positive ones a partially complementary distribution pattern was found. Calbindin-like immunoreactive portions of the anterior olfactory nucleus and olfactory tract were mirrored by immunonegative areas in adjacent sections stained for parvalbumin. Using the combined pigment-Nissl procedure we observed the presence of lipofuscin deposits in nearly 80% of all the calbindin-immunoreactive neurons analysed. Moreover, analysis of their lipofuscin deposits rendered the further differentiation of morphologically similar neuronal subpopulations possible. In contrast, all parvalbumin-like immunoreactive neurons remained free of lipofuscin granules.

Adult↗
PubMed2003

Grouping of odorant receptors: odour maps in the mammalian olfactory bulb.

The olfactory system is unique in that the sensory input is in the form of molecular information carried in a vast variety of odorants. Nearly 1000 types of odorant receptors mediate the initial detection and discrimination of odorants at the molecular-feature level. The discrimination at the molecular level is converted into that at the cellular level (olfactory sensory neurons) by the one sensory neuron-one odorant receptor rule, and then into that at the neuronal circuit level in the olfactory bulb by the specific olfactory axon connectivity pattern. Individual glomeruli in the olfactory bulb represent a single odorant receptor, and the glomerular sheet at the olfactory bulb surface forms odorant receptor maps. This review focuses on the spatial organization of the glomerular sensory map in the olfactory bulb. The analysis using the optical imaging method suggests that odorant receptors having a common molecular-feature receptive site are grouped together and represented by glomeruli that are localized in topographically fixed domains in the olfactory bulb. The domain organization may be a structural unit for the spatial organization of the glomerular sensory map, and might relate to the olfactory submodality.

Animals↗
PubMed1995

Evidence that pioneer olfactory axons regulate telencephalon cell cycle kinetics to induce the formation of the olfactory bulb.

Early olfactory axons follow a specific pathway to reach the developing telencephalon. We observed that a subpopulation of these axons, the pioneer olfactory axons, penetrate into the ventricular zone of a highly restricted region of the telencephalon at E13 and E14. At E15, this same telencephalic region evaginates to form the olfactory bulb. To investigate the possibility that the pioneer olfactory axons induce the olfactory bulb by influencing precursor cell populations, we compared cell cycle kinetics and differentiation in the olfactory bulb primordium and the adjacent neocortex using cumulative bromdeoxyuridine labeling. The results showed that, 24 hr after the arrival of the first pioneer axons, the duration of the cell cycle is prolonged significantly in the olfactory bulb primordium. In addition, twice as many cells have exited the mitotic cycle in the olfactory bulb primordium versus the adjacent cortex. These findings suggest that pioneer olfactory axons play a role in the induction of the olfactory bulb by selectively modulating cell cycle kinetics in the olfactory bulb primordium. Afferent axons may influence target morphogenesis by modulating target precursor cell proliferation in other developing neural structures.

Animals↗
PubMed2006

Long-term fate and distribution of newborn cells in the adult mouse olfactory bulb: Influences of olfactory deprivation.

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.

Analysis of Variance↗
PubMed2001

Bilateral olfactory deprivation reveals a selective noradrenergic regulatory input to the olfactory bulb.

Unilateral olfactory deprivation in the rat induces changes in the catecholaminergic system of the olfactory bulb. Nevertheless, evidence suggests that unilateral deprivation does not fully prevent stimulation of the deprived bulb. The present report analyses the response of the catecholaminergic system of the olfactory bulb in fully deprived rats obtained by bilateral naris occlusion. The complete deprivation produces more rapid and dramatic changes in both the intrinsic and extrinsic catecholaminergic systems of the olfactory bulb. Intrinsic responses involve a rapid decrease in dopamine-containing cells to about 25% of controls, correlated with a decreased Fos expression in juxtaglomerular cells of all olfactory glomeruli, with the only exception of those of the atypical glomeruli which maintain unaltered expression of both markers. In parallel with these events, there is a progressive increase in the density of extrinsic noradrenergic axons arising from neurons in the locus coeruleus, which shows, in parallel, a progressive increase in Fos expression. This model demonstrates plastic changes in the catecholaminergic system of the olfactory bulb forming a valid morphological substrate for lowering thresholds in the processing of olfactory information. In addition to this generalized response, there is another one, directed to a specific subset of olfactory glomeruli (atypical glomeruli) involved in the processing of odor pheromone-like cues related to behavioral responses, that could be responsible for keeping active this reduced and selected group of glomeruli carrying crucial olfactory information. These results indicate the existence of adaptive changes in the catecholaminergic system of the olfactory bulb as a response to the lack of afferent peripheral stimulation. These changes involve dopamine- and noradrenaline-immunoreactive elements, in a strategy presumably directed at maintaining to the highest possible level the ability to detect olfactory signals.

Afferent Pathways↗
PubMedDate not supplied

Developmental and aging aspects of the cholinergic innervation of the olfactory bulb.

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.

Acetylcholine↗
PubMed1989

Experimental studies on the olfactory marker protein. V. Olfactory marker protein in the olfactory neurons transplanted within the olfactory bulb.

The olfactory mucosa of neonatal rats was transplanted within the olfactory bulb of littermates to investigate whether the olfactory bulb would have played a role in the differentiation of the olfactory neurons and whether the olfactory axons, growing out from the transplant, would have interacted with the olfactory glomeruli of the host. The observations were conducted on sections stained with Gill's hematoxylin, Loots' silver method, and the immunohistochemical technique for the demonstration of the olfactory marker protein (OMP). The olfactory neurons of the transplant (those localized in the neuroepithelium and those migrating from it into the bulbar parenchyma) could become fully differentiated but only few of them were OMP positive. Numerous sensory axons originated from the transplanted olfactory mucosa, however, they did not form ectopic glomeruli nor did they interact with the glomeruli of the host. These results indicate that the olfactory bulb, in vivo, does not affect the number of olfactory neurons expressing OMP and that the ectopically located neurons lack the cues to recognize the host glomeruli.

Animals↗
PubMed2001

Distinct distribution of four Ca2+-dependent subtypes of protein kinase C in rat olfactory bulb; definite expression of betaII-subtype in the accessory olfactory bulb.

The localization of four subtypes of Ca2+-dependent protein kinase C (PKC) in the main and accessory olfactory bulb was examined by immunocytochemistry by using specific antibodies against each PKC subtype. In the main olfactory bulb, alpha-PKC was densely localized in a large number of granule cells and in a few tufted cells, and faint immunoreactivity was seen in some periglomerular cells. betaI-PKC was intensely found in periglomerular cells and tufted cells. gamma-PKC immunoreactivity was present in the external plexiform layer, the internal plexiform layer, and the granular layer, but the immunoreactivity was found only in the neuropils. Little, if any, betaII-PKC was seen in the main olfactory bulb. On the other hand, the intense immunoreactivity for betaII-PKC was seen in periglomerular cells of the accessory olfactory bulb. The betaI-PKC and gamma-PKC were also present in periglomerular cells of the accessory olfactory bulb, while alpha-PKC was localized only in granule cells. Double staining study in the accessory olfactory bulb showed that betaII-PKC was present in the GABAergic periglomerular cells, while betaI-PKC localized to the non-GABAergic periglomerular cells; gamma-PKC was expressed in both GABAergic and non-GABAergic cells. These findings suggest that four calcium-dependent subtypes of PKC play different roles in the olfactory bulb and definite expression of betaII-PKC strongly suggested the involvement of this subtype in a specific function in the accessory olfactory bulb.

Animals↗
PubMed1984

Transneuronal degeneration in different inbred strains of mice: a preliminary study of olfactory bulb events after olfactory nerve lesion.

Cytological analysis of the olfactory bulb was performed in two inbred strains of mice SEC/1 ReJ and C57/B16J after the lesion of the olfactory nerve. The data show an enhanced transneural degeneration in C57 mice as compared to the controls, while in the SEC mice this phenomenon did not exceed the level of spontaneous degeneration previously described by other authors. On the basis of our findings two different genetically adaptive systems are hypothesized and correlated with onto-genetical data.

Animals↗
PubMed2006

Adjusting neurophysiological computations in the adult olfactory bulb.

The olfactory bulb receives signals from olfactory sensory neurons and conveys them to higher centers. The mapping of the sensory inputs generates a reproducible spatial pattern in the glomerular layer of the olfactory bulb for each odorant. Then, this restricted activation is transformed into highly distributed patterns by lateral interactions between relay neurons and local interneurons. Thus, odor information processing requires the spatial patterning of both sensory inputs and synaptic interactions. In other words, odor representation is highly dynamic and temporally orchestrated. Here, we describe how the local inhibitory network shapes the global oscillations and the precise synchronization of relay neurons. We discuss how local inhibitory interneurons transpose the spatial dimension into temporal patterning. Remarkably, this transposition is not fixed but highly flexible to continuously optimize olfactory information processing.

Animals↗
PubMed1988

Effects of locus ceruleus and olfactory bulb stimulation on rat olfactory tubercle neuron activity.

The effects of electrical stimulation of the olfactory bulb and the locus ceruleus on olfactory tubercle neurons were examined in rat models. Ipsilateral stimulation of the olfactory bulb produced excitation in 31% of olfactory tubercle neurons tested and inhibition in 17%. Twenty-two percent of the olfactory tubercle neurons were excited, whereas 9% were inhibited by ipsilateral stimulation of the locus ceruleus. Contralateral stimulation of the locus ceruleus produced similar responses in the same neuron entities. A negative-positive evoked potential was recorded in the olfactory tubercle after ipsilateral and contralateral stimulation of the locus ceruleus. Thirty-three percent of the olfactory tubercle neurons that responded orthodromically or antidromically to stimulation of the olfactory bulb were excited by ipsilateral stimulation of the locus ceruleus. In contrast, only 10% responded with excitation to ipsilateral stimulation of the locus ceruleus among the olfactory tubercle neurons that were unresponsive to stimulation of the olfactory bulb. These findings suggest that olfactory tubercle neurons that receive input from or sending output to the olfactory bulb are influenced by the noradrenergic system of the locus ceruleus. A possible role of the olfactory tubercle in olfactory transduction will also be discussed.

Animals↗