Number Of Mitral Cells Research Articles

Neuronal scaling in the olfactory system of bats.

Comparative studies are a common way to address large-scale questions in sensory biology. For studies that investigate olfactory abilities, the most commonly used metric is olfactory bulb size. However, recent work has called into question the broad-scale use of olfactory bulb size. In this paper, we use three neuroanatomical measures with a more mechanistic link to olfactory function (number of olfactory sensory neurons (OSNs), number of mitral cells (MCs), and number of glomeruli) to ask how species with different diets may differ with respect to olfactory ability. We use phyllostomid bats as our study system because behavioral and physiological work has shown that fruit- and nectar-feeding phyllostomids rely on odors for detecting, localizing, and assessing potential foods, while insect-eating species do not. Therefore, we predicted that fruit- and nectar-feeding bats would have larger numbers of these three neuroanatomical measures than insect-eating species. In general, our results supported the predictions. We found that fruit-eaters had greater numbers of OSNs and glomeruli than insect-eaters, but we found no difference between groups in number of MCs. We also examined the allometric relationship between the three neuroanatomical variables and olfactory bulb volume, and we found isometry in all cases. These findings lend support to the notion that neuroanatomical measures can offer valuable insights into comparative olfactory abilities, and suggest that the size of the olfactory bulb may be an informative parameter to use at the whole-organism level.

Species Specific Structural Differences of the Main Olfactory Bulbs in Dog (Canis Familiaris) and Goat (Capra Hircus)

The structural characteristic of the main olfactory bulb (MOB) shows species-dependent variations. However, the correlation of such structure with olfactory function as well as with the ecological and evolutionary behaviours is less understood. Therefore, the aim of the current investigation was to elucidate the species differences of the structure of MOB in two ecologically diverse species, dogs and goats. For that purpose, thirteen heads of each species were obtained. The brains and the olfactory bulbs were dissected for anatomical, histological and immunohistochemical analyses for detection of glial fibril acidic protein (GFAP) and chromogranin A. Anatomically, the volume of the olfactory bulb to the whole brain volume was higher in dogs (1.74%) than goats (0.57%). Histologically, the main olfactory bulbs were organized in the following layers: the olfactory nerve layer (ONL), the glomerular layer (GL), the external plexiform layer (EPL), the mitral cell layer (MCL), internal plexiform layer (IPL) , the granule cell layer (GCL) and a periventricular layer (PVL). Enormous number of juxtaglomerular and mitral cells, thickness of GL, EPL and GCL were significantly greater in dogs than goats. Immunohistochemically, the integrated density percentage of GFAP and chromogranin A was significantly higher in dogs than goats. The average number of mitral cell neurons in a standard area was significantly higher in dogs (6 ±.37) than goats (3.16 ±.31). Therefore, our data suggested that such apparent structural difference of MOB between the dog and the goat could be correlated with superior olfactory sensitivity and subsequently the ecological and lifestyle behaviour of dogs.

Anatomical evidence for scent guided foraging in the turkey vulture

The turkey vulture (Cathartes aura) is a widespread, scavenging species in the Western Hemisphere that locates carrion by smell. Scent guided foraging is associated with an expansion of the olfactory bulbs of the brain in vertebrates, but no such neuroanatomical data exists for vultures. We provide the first measurements of turkey vulture brains, including the size of their olfactory bulbs and numbers of mitral cells, which provide the primary output of the olfactory bulbs. Comparative analyses show that the turkey vulture has olfactory bulbs that are 4× larger and contain twice as many mitral cells as those of the sympatric black vulture (Coragyps atratus), despite having brains that are 20% smaller. The turkey vulture has the largest olfactory bulbs in absolute terms and adjusted for brain size among birds, but the number of mitral cells is proportional to the size of their olfactory bulbs. The combination of large olfactory bulbs, high mitral cell counts and a greatly enlarged nasal cavity likely reflects a highly sensitive olfactory system. We suggest that this sensitive sense of smell allowed the turkey vulture to colonize biomes that are suboptimal for scavenging birds and become the most widespread vulture species in the world.

A study ofthe morphogenesis & mitral cell population of human fetal olfactory bulbs

Abstract Background and Aims: Human fetal olfactory bulbs have a six layered laminar architecture where mitral cells are the largest neurons. Volume of the bulbs is considered as an indicator of olfactory function. Fetal bulb cell transplants are used to treat many diseases of the central nervous system. The present study aims to trace the development of the fetal bulbs with respect to it’s gross appearance, volume, arrangement and the number of mitral cells. Materials and Methods: Sixty two normal fresh aborted fetuses were collected from Obstetrics and Gynaecology department of Regional Institute of Medical Sciences, Imphal. The fetuses were dissected and olfactory bulbs were gently taken out and fixed in 10& formal saline. Once fixed, the volume of the bulbs were measured using a measuring cylinder and insulin syringe. This was followed by tissue processing and staining with Toluidine Blue and Cresyl Violet. Stained slides were photographed and number of mitral cells were counted using Image J software. The correlation of bulb volume with fetal age, crown rump length [CRL 1 and fetal body weight was analysed using SPSS software. Similar analysis was also done between mitral cell number and fetal age. Result: Fetal bulbs attained adult morphology at 20 weeks. Bulb volume was found to rise significantly with advancing fetal age until it slowed down 32 weeks onwards. Mitral cells were identifiable at 16 weeks and maintained a laminar arrangement and showed progressive increase in number until 28 weeks. There after the orderly arrangement of cells as well their number declined. Conclusion: Very few studies have been conducted so far regarding the fetal olfactory bulbs in India. The present study is expected to supplement known data and knowledge regarding the development of the fetal bulbs and the mitral cell population and help in the diagnosis and treatment of central nervous system diseases.

Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb.

Collapsin response mediator protein 4 (CRMP4), a member of the CRMP family, is involved in the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Here, we first compared layer thickness of the olfactory bulb between wild-type (WT) and CRMP4-knockout (KO) mice. The mitral cell layer (MCL) was significantly thinner, whereas the external plexiform layer (EPL) was significantly thicker in CRMP4-KO mice at postnatal day 0 (PD0) compared with WTs. However, differences in layer thickness disappeared by PD14. No apoptotic cells were found in the MCL, and the number of mitral cells (MCs) identified with a specific marker (i.e. Tbx21 antibody) did not change in CRMP4-KO neonates. However, DiI-tracing showed that the length of mitral cell apical dendrites was greater in CRMP4-KO neonates than in WTs. In addition, expression of CRMP4 mRNA in WT mice was most abundant in the MCL at PD0 and decreased afterward. These results suggest that CRMP4 contributes to dendritic elongation. Our invitro studies showed that deletion or knockdown of CRMP4 resulted in enhanced growth of MAP2-positive neurites, whereas overexpression of CRMP4 reduced their growth, suggesting a new role for CRMP4 as a suppressor of dendritic elongation. Overall, our data suggest that disruption of CRMP4 produces a temporary alteration in EPL thickness, which is constituted mainly of mitral cell apical dendrites, through the enhanced growth of these dendrites.

Tag1 deficiency results in olfactory dysfunction through impaired migration of mitral cells.

The olfactory system provides mammals with the abilities to investigate, communicate and interact with their environment. These functions are achieved through a finely organized circuit starting from the nasal cavity, passing through the olfactory bulb and ending in various cortical areas. We show that the absence of transient axonal glycoprotein-1 (Tag1)/contactin-2 (Cntn2) in mice results in a significant and selective defect in the number of the main projection neurons in the olfactory bulb, namely the mitral cells. A subpopulation of these projection neurons is reduced in Tag1-deficient mice as a result of impaired migration. We demonstrate that the detected alterations in the number of mitral cells are well correlated with diminished odor discrimination ability and social long-term memory formation. Reduced neuronal activation in the olfactory bulb and the corresponding olfactory cortex suggest that Tag1 is crucial for the olfactory circuit formation in mice. Our results underpin the significance of a numerical defect in the mitral cell layer in the processing and integration of odorant information and subsequently in animal behavior.

Odor enrichment sculpts the abundance of olfactory bulb mitral cells

Mitral cells are the primary output cell from the olfactory bulb conveying olfactory sensory information to higher cortical areas. Gene-targeted deletion of the Shaker potassium channel Kv1.3 alters voltage-dependence and inactivation kinetics of mitral cell current properties, which contribute to the “Super-smeller” phenotype observed in Kv1.3-null mice. The goal of the current study was to determine if morphology and density are influenced by mitral cell excitability, olfactory environment, and stage of development. Wildtype (WT) and Kv1.3-null (KO) mice were exposed to a single odorant (peppermint or citralva) for 30 days. Under unstimulated conditions, postnatal day 20 KO mice had more mitral cells than their WT counterparts, but no difference in cell size. Odor-enrichment with peppermint, an olfactory and trigeminal stimulus, decreased the number of mitral cells in three month and one year old mice of both genotypes. Mitral cell density was most sensitive to odor-stimulation in three month WT mice. Enrichment at the same age with citralva, a purely olfactory stimulus, decreased cell density regardless of genotype. There were no significant changes in cell body shape in response to citralva exposure, but the cell area was greater in WT mice and selectively greater in the ventral region of the OB in KO mice. This suggests that trigeminal or olfactory stimulation may modify mitral cell area and density while not impacting cell body shape. Mitral cell density can therefore be modulated by the voltage and sensory environment to alter information processing or olfactory perception.

Sparse Incomplete Representations: A Potential Role of Olfactory Granule Cells

Mitral/tufted cells of the olfactory bulb receive odorant information from receptor neurons and transmit this information to the cortex. Studies in awake behaving animals have found that sustained responses of mitral cells to odorants are rare, suggesting sparse combinatorial representation of the odorants. Careful alignment of mitral cell firing with the phase of the respiration cycle revealed brief transient activity in the larger population of mitral cells, which respond to odorants during a small fraction of the respiration cycle. Responses of these cells are therefore temporally sparse. Here, we propose a mathematical model for the olfactory bulb network that can reproduce both combinatorially and temporally sparse mitral cell codes. We argue that sparse codes emerge as a result of the balance between mitral cells' excitatory inputs and inhibition provided by the granule cells. Our model suggests functional significance for the dendrodendritic synapses mediating interactions between mitral and granule cells.

Stabilisation of beta and gamma oscillation frequency in the mammalian olfactory bulb

The dynamics of the mammalian olfactory bulb (OB) is characterized by local field potential (LFP) oscillations either slow, in the theta range (2-10Hz, tightly linked to the respiratory rhythm), or fast, in the beta (15-30Hz) or gamma (40-90Hz) range. These fast oscillations are known to be modulated by odorant features [1] and animal experience or state [2][3], but both their mechanisms and implication in coding are still not well understood. In this study, we used a double canulation protocol to impose artificial breathing rhythms to anesthetized rats while recording the LFP in the OB. We observed that despite the changes in the input air flow parameters (frequency or flow rate), the main characteristics of fast oscillations (duration, frequency or amplitude) were merely constant. We thus made the hypothesis that fast beta and gamma oscillations dynamics are entirely determined by the OB network properties and that external stimulation was only able put the network in a state which permits the generation of one or the other oscillations (they are never present simultaneously). To test this hypothesis, we studied a simplified OB model based on previous modeling studies. In particular it includes resonant mitral cells [4] and graded synaptic inhibition [5]. Detailed analysis and numerical simulations of the model showed that two oscillatory dynamical regime can be sustained. First, a low noise regime where at each cycle, a subset of mitral cells are tightly synchronized and yield a saturation of the graded inhibition, during which mitral cell discharge is prevented. Because of this saturation, the network frequency is governed by the dynamics of the graded inhibition decay. Interestingly, this dynamics is not very sensitive to the number of mitral cells that lead to the saturation. Consequently, there is a wide range of mitral cell firing rate during which the network frequency is stable. Using standard parameters in our model, we found an oscillation frequency stable between 25 and 30Hz while the average mitral cell firing rate increased from 5Hz to 25Hz. Second, a high noise regime can be observed where the mitral cell discharge is much less regular. In this case, the network oscillations are of lower amplitude compared to the low noise regime and thus the graded inhibition is never saturated by fluctuations around its mean. The network can then be well described by a mean field approach (as described in [ 6]) and is close to a previous model of in vitro gamma oscillations [4]. With our model parameters, oscillations in this regime have higher frequency, typically in the gamma range (50Hz-90Hz) but their frequency is highly sensitive to the level of input excitation to the mitral cells. This discrepancy with our experimental result could be relieved by the in vitro experimental observation that mitral cell stimulus excitatory input is all or none [7]. Indeed this could provide a stable external input to the network and thus also stabilize the gamma frequency. Finally, we have shown that our model can account for the two stable oscillatory regimes observed in the OB in vivo. However our model does not take into account the spatial activation of the OB and the study of how spatially segregated oscillatory generators interact and potentially synchronize is an ongoing work.

A practical demonstration of the computational benefits of biophysical diversity among neurons

Across a variety of brain areas, physiological characterizations of neurons have revealed that neurons of the same subtype often display different biophysical properties from one another. Here we propose that when considering a population of neurons these inter-neuronal differences can be utilized by the population to enhance encoding of a stimulus. Specifically, we demonstrate that a population of neurons with heterogeneous feature selectivity across the population can represent more about a stimulus than a population of neurons with identical feature selectivity. Using a paradigm of an identical frozen noise current injection stimulus delivered to a population of neurons, we simulated the responses of populations of neurons with differing degrees of heterogeneity in their feature selectivity. We simulated neurons using the Linear-Nonlinear-Poisson (LNP) neuron model and constructed neurons selective to different features of the stimulus by varying the stimulus filter of each LNP neuron. To calculate the information encoded in the spike responses of different populations of neurons, we used information theoretic measures as well as optimal Bayesian stimulus reconstruction methods. Stimulus reconstruction methods are particularly useful in this context because they allow us to visualize which particular stimulus features are able to be encoded by different populations. We found that stimulus reconstructions computed from responses of heterogeneous neurons were more accurate than responses from homogenous neurons. Finally, we recorded spike responses in vitro from a number of mitral cells from the mouse olfactory bulb while stimulating each cell with an identical current injection stimulus. Based on the similarity of each neuron’s spike triggered average, an indication of the neuron’s feature selectivity, we grouped neurons into virtual homogenous and heterogeneous populations. As above we found that populations composed of heterogeneous neurons encoded more information about the stimulus input than homogenous populations. Though inter-neuronal diversity is often thought of as a negative consequence of the inability of biology to make identical copies of the same neuron, our results indicate that neuronal diversity may in fact be utilized positively by the brain.

Morphological and quantitative features of mitral cells in the rat olfactory bulb after administration of propranolol.

To determine the cytoplasmic morphological changes in the mitral cells and quantitative changes (number of mitral cells and thickness of mitral cell layer in microns) in the rat olfactory bulb after administration of propranolol. Experimental study. The Department of Anatomy, University of Health Sciences, Lahore, from January 2006 to January 2007. Twenty samples were obtained from two randomly divided groups of rats, each comprising 10 animals for control and experimental work respectively. Each group was treated with normal saline (5 ml/kg) and propranolol (1 mg/kg) respectively for one month. The skull was fixed in 20% formalin for 10 days and decalcified in 10% formalin/10% nitric acid. The olfactory bulb along with olfactory cortex was dissected. After processing, 10 microns thick sections were obtained. The slides were stained with Hematoxylin and Eosin and Bielschowksy's silver stain (Glees-Marsland modification) and studied under light microscope. The morphology, quantitative analysis of mitral cell layer and the number of mitral cells were studied in the histological study and compared using t-test with significance at p < 0.05. In the propranolol treated group changes observed in the morphology of the mitral cells included presence of cytoplasmic vacuoles at the periphery of the cells. There was significant increase in the thickness of mitral cell layer and number of the mitral cell in the propranolol treated group (p < 0.05). This study showed morphological and quantitative changes in the olfactory bulb in response to treatment with propranolol, hence it has implications in odour induced learning.

Molecular diversity of deep short‐axon cells of the rat main olfactory bulb

Local circuit GABAergic interneurons comprise the most diverse cell populations of neuronal networks. Interneurons have been characterized and categorized based on their axo-somato-dendritic morphologies, neurochemical content, intrinsic electrical properties and their firing in relation to in-vivo population activity. Great advances in our understanding of their roles have been facilitated by their selective identification. Recently, we have described three major subtypes of deep short-axon cells (dSACs) of the main olfactory bulb (MOB) based on their axo-dendritic distributions and synaptic connectivity. Here, we investigated whether dSACs also display pronounced molecular diversity and whether distinct dSAC subtypes selectively express certain molecules. Multiple immunofluorescent labeling revealed that the most commonly used molecular markers of dSACs (e.g. vasoactive intestinal polypeptide, calbindin and nitric oxide synthase) label only very small subpopulations (< 7%). In contrast, voltage-gated potassium channel subunits Kv2.1, Kv3.1b, Kv4.3 and the GABA(A) receptor alpha1 subunit are present in 70-95% of dSACs without showing any dSAC subtype-selective expression. However, metabotropic glutamate receptor type 1alpha mainly labels dSACs that project to the glomerular layer (GL-dSAC subtype) and comprise approximately 20% of the total dSAC population. Analysing these molecular markers with stereological methods, we estimated the total number of dSACs in the entire MOB to be approximately 13,500, which is around a quarter of the number of mitral cells. Our results demonstrate a large molecular heterogeneity of dSACs and reveal a unique neurochemical marker for one dSAC subtype. Based on our results, dSAC subtype-specific genetic modifications will allow us to decipher the role of GL-dSACs in shaping the dynamic activity of the MOB network.

Molecular characterization of deep short-axon cells of the rat main olfactory bulb

Event Abstract Back to Event Molecular characterization of deep short-axon cells of the rat main olfactory bulb Mark Eyre1*, Katalin Kerti1 and Nusser Zoltan1 1 Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary The most diverse cell populations of neuronal networks are local circuit GABAergic interneurons, and our ability to selectively identify and study them has greatly advanced our understanding of their roles. Interneurons have been classified based on their morphologies, neurochemical content and electrical properties. We recently identified three major subtypes of deep short-axon cells (dSACs) of the main olfactory bulb (MOB) based on their axo-dendritic distributions and synaptic connectivity. Here, we investigated the molecular diversity of dSACs and asked whether distinct dSAC subtypes selectively express certain molecules. Immunofluorescent colocalization experiments revealed that the most commonly used molecular markers of dSACs (i.e. VIP, SOM, CB, NOS) label only very small subpopulations (<7%). In contrast, the voltage-gated potassium channel subunits Kv2.1, Kv3.1b, Kv4.3 and the GABAA receptor α1 subunit are present in 70-95% of dSACs. However, none of these molecules are dSAC-subtype-selective, despite their heterogenous expression levels. Further experiments revealed that mGluR1α labels 22% of the total dSAC population, mostly cells located in the internal plexiform layer. Whole-cell recorded and morphologically identified dSACs immunoreactive for mGluR1α were GL-dSACs, whereas immunonegative dSACs were not. Retrograde tracing of projection dSACs indicated heterogenous expression of several molecules, although none were subtype-selective. Using stereological methods, we estimated the total number of dSACs in the entire MOB to be ~13500, which is around one fourth of the number of mitral cells. Our results provide the first estimate of the total number of dSACs, demonstrate their large molecular heterogeneity and reveal a unique neurochemical marker for one dSAC subtype. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Developmental neurobiology and subcortical functions Citation: Eyre M, Kerti K and Zoltan N (2009). Molecular characterization of deep short-axon cells of the rat main olfactory bulb. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.052 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Feb 2009; Published Online: 27 Feb 2009. * Correspondence: Mark Eyre, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, eyre@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mark Eyre Katalin Kerti Nusser Zoltan Google Mark Eyre Katalin Kerti Nusser Zoltan Google Scholar Mark Eyre Katalin Kerti Nusser Zoltan PubMed Mark Eyre Katalin Kerti Nusser Zoltan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Age and gender-related differences in mitral cells of olfactory bulb.

To investigate the age and gender-related differences in mitral cells of the human cadaveric olfactory bulbs. A cross-sectional study. The study was conducted in the Department of Anatomy, University of Health Sciences, Lahore, from August 2005 to July 2007. Sixty olfactory bulbs, 30 each from male and female (age 20-76 years) human cadavers divided into six groups of age and gender-wise were collected from the mortuary of the King Edward Medical University, Lahore. Mitral cells were counted and their diameter was calculated from 10 microm thick cresyl violet stained histological sections. Statistical analysis was done using ANOVA for age-related differences and independent t-test for gender-related differences. There was significant reduction in the number of mitral cells and diameter of their nuclei with age. There was significant decrease in the number of mitral cells in males, between groups I and II (p < 0.001); II and III (p < 0.001); and I and III (p < 0.001); statistically significant decrease also occurred in females, between groups IV and V (p < 0.001); V and VI (p < 0.001); and IV and VI (p < 0.001). In most cases, the distance between individual mitral cells was seen to be much greater than in younger group. In group VI, few mitral cells were observed in the cell layer. There was also significant decrease in the diameter of mitral cell nuclei in males, between groups I and III (p < 0.001); and II and III (p < 0.010); in females, between groups IV and VI (p < 0.001); and V and VI (p < 0.001). No gender-related differences were observed. The number of mitral cells and diameter of their nuclei decreased with advancing age.

Environmental prenatal stress alters sexual dimorphism of maternal behavior in rats

The prenatal external environment can affect fetuses, altering the maternal behavior that they express when mature. In the present study, environmental prenatal stress (EPS) was applied to pregnant rats in their final week of gestation, and when their female offspring reached maturity, the long latency effect of the stress on those offspring was ascertained on their induced maternal behavior (MB), accessory olfactory bulb (AOB) morphology and plasma levels of ACTH and corticosterone (Cpd B). EPS reduced: the percentage of these virgins that showed induced MB, their retrieval of foster pups, the time spent crouching, and the quality of nest building; it also increased the incidence of their cannibalism of foster pups. The EPS-treated females presented a male-like pattern of induced MB. They showed increased plasma levels of ACTH and Cpd B and increased numbers of mitral cells in the AOB. These findings provide evidence that stress applied to the pregnant rat produces long-lasting behavioral, neuroanatomical and hormonal alterations in the female offspring that can be observed when they reach maturity.

Deeply located granule cells and mitral cells undergo apoptosis after transection of the central connections of the main olfactory bulb in the adult rat

The main olfactory bulb (MOB) is the first relay station of the olfactory system: it receives afferents from sensory neurons and sends efferents to the primary olfactory cortex. The MOB also receives many centrifugal afferents from various regions. Transection of peripheral afferents to the MOB has been reported to induce cell death in granule cells. However, little is known about the effect of transection of these central connections of the MOB in adult rats. Here, we used a unilateral olfactory peduncle transection model in the adult rat to examine neuronal degeneration in the MOB. In the MOB ipsilateral to the surgery, the granule cell layer (GCL) was smaller, and the number of mitral cells was decreased compared with the contralateral MOB at 7 days after surgery. Many degenerating cells were present in both the mitral cell layer (MCL) and GCL in the ipsilateral MOB at 3 days after surgery, although there were no obvious changes in the gross morphology. We also found terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells in the MCL and GCL in the ipsilateral MOB at 3 days after surgery. The majority of the degenerating and TUNEL-positive cells were located in the deep, rather than the superficial, GCL. Immunohistochemistry for activated caspase-9 further supported the occurrence of apoptotic cell death in the mitral and deeply located granule cells. These results indicate that not only axotomized mitral cells, but also deeply located granule cells that were not directly injured, underwent apoptosis after transection of the central connections, and suggest that sensitivities to transection of the central connections differ among granule cells according to their depth in the GCL.

Neurobiological mechanisms involved in recognition of olfactory signature of the young in sheep.

The following review focuses on neurobiological mechanisms responsible for the individual recognition of the olfactory signature of the young by the ewe at parturition. Steroids and vaginocervical stimulation are responsible for neurochemical and electrophysiological changes within the olfactory bulb that are part of the learning mechanisms of the individual lamb odour, thus allowing the establishment of a selective bond between the ewe and her lamb. There is an increase in the number of mitral cells, the principal cells of the olfactory bulb that respond to lamb odours, which is associated with increased release of glutamate and gamma-aminobutyric acid from the dendrodendritic synapses between the mitral and granule cells. The relation between the release of the two transmitters after birth suggests an increased efficacy of glutamate evoked gamma-aminobutyric acid release. Parturition is also accompanied by increased oxytocinergic, cholinergic and noradrenergic neurotransmitter release that are essential for selective recognition of lambs. These increases in transmitter release depend on maternal experience, so that greater amounts have been found in multiparous than primiparous ewes. Therefore maternal experience seems to induce a neural maturation process that facilitates effective transmitter release in the olfactory bulb.

Functional consequences following infection of the olfactory system by intranasal infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM.

The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a `go, no-go' successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 μl of the OBLV stock per nostril for a total of 1.5 × 106 p.f.u. in 600 μl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals.

Focal denervation alters cellular phenotypes and survival in the developing rat olfactory bulb

Several studies have demonstrated that contact between the olfactory nerve and the forebrain is critical for normal olfactory bulb development. Removal of the embryonic olfactory placode results in a failure of the olfactory bulb to form, as well as causing other forebrain malformations. The current study introduces a technique that permits removal of contact between specific regions of the olfactory nerve and the bulb early in development, without causing damage to other brain regions, and without removing the peripheral olfactory organ. The manipulation, which involves insertion of a small Teflon chip between the cribriform plate and the bulb, prohibits growth of new axons into the "shadow" region behind the implant. Focal denervation of the olfactory bulb causes a decrease in bulb and layer sizes, a reduction in mitral cell number, and changes to bulb architecture. Using a battery of antibodies (OMP, MAP2, TuJ1, calretinin, calbindin, parvalbumin, TH, and GAD), we further demonstrated that 1) focal denervation alters the relationship between the olfactory nerve and the bulb, 2) the fine structure of cells in denervated regions is disrupted, and 3) cellular phenotypes change in response to loss of afferent contact. These results suggest that contact between the olfactory nerve and the bulb is important for maintaining bulb architecture and cell survival, structure, and phenotype. They also point to focal denervation as a useful technique for examining the role of neural contact in olfactory development and maintenance of the central nervous system.

Effects of Alcohol and Nicotine on Developing Olfactory Bulb: Loss of Mitral Cells and Alterations in Neurotransmitter Levels

Previous research from our laboratory has shown that [ethanol (EtOH)] exposure during the brain growth spurt is detrimental to olfactory bulb development. This study extends those findings by examining the effects of EtOH, nicotine (NIC), and the combination of these drugs (EtOH/NIC) on olfactory bulb mitral cell numbers, as well as on various major neurotransmitter levels in neonatal rats. An artificial rearing paradigm was used in the present studies. These artificially reared pups were given 4 g/kg/day of EtOH and/or 6 mg/kg/day of NIC on postnatal day (PD) 4 to PD 9, except in the case of the acute neurochemistry study, in which the pups received treatment on PD 9 only. An artificially reared gastrostomy control group (GC) and a suckle control group were included. The mean total numbers of mitral cells in the EtOH and NIC groups were significantly reduced from that of the GC, as well as the volume of the left main olfactory bulb. There was no difference among any of the groups in mitral cell density. As for neurochemistry data, there was no difference in neurotransmitter levels among any of the groups in the repeat exposure regimen. There were, however, changes after the acute exposure (exposure on PD 9 only). Both serotonin and GABA levels were significantly increased only after NIC exposure. However, norepinephrine levels were significantly decreased after acute exposure in all three drug treatment groups, compared with that of the control group. Except for the GC control group, dopamine levels were not detected consistently after acute exposure to EtOH, NIC, or EtOH/NIC. Collectively, these findings demonstrate that exposure to EtOH or NIC individually during the brain growth spurt results in developmental deficits in the olfactory bulb, suggesting that both EtOH and NIC are neuroteratogens. Furthermore, this study demonstrated the capability of NIC to antagonize (protect) EtOH-induced mitral cell loss in the developing olfactory bulb.