Nitric oxide mediates the formation of synaptic connections in developing and regenerating olfactory receptor neurons

Nitric oxide (NO) is a diffusible free radical that functions as a second messenger and neurotransmitter. NO synthase (NOS) is highly and transiently expressed in neurons of the developing olfactory epithelium during migration and establishment of primary synapses in the olfactory bulb. NOS is first expressed at E11 in cells of the presumptive nervous layer of the olfactory placode. NOS immunoreactivity persists in the descendants of these cells that differentiate into embryonic olfactory receptor neurons (ORNs). Olfactory NOS expression in the ORN and in its afferents rapidly declines after birth and is undetectable by P7. Following bulbectomy, NOS expression is rapidly induced in the regenerating ORN and is particularly enriched in their outgrowing axons. Immunoblot and Northern blot analyses similarly demonstrate an induction of NOS protein and mRNA expression, respectively, the highest levels of which coincide with peaks of ORN regeneration. These data argue against a role for NO in odorant-sensitive signal transduction, but suggest a prominent function for NO in activity-dependent establishment of connections in both developing and regenerating olfactory neurons.     

Olfactory-evoked regional cerebral blood flow in Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). It was hypothesized that AD would reduce olfactory-evoked perfusion in mesial temporal olfactory (piriform) cortex, where neuropathology begins. Seven AD patients and 8 elderly controls (ECs) underwent olfactory threshold and identification tests and olfactory stimulation during positron emission tomography. Odor identification was impaired in AD, but threshold was not. Olfactory stimulation in ECs activated right and left piriform areas and right anterior ventral temporal cortex. AD patients had less activation in right piriform and anterior ventral temporal cortex but not in the left piriform area. Although orbital cortex did not activate in ECs, there was a significant between-groups difference in this area. Right piriform activation correlated with odor identification. Impaired odor identification likely reflects sensory cortex dysfunction rather than cognitive impairment. Given olfactory bulb projections to the mesial temporal lobe, olfactory stimulation during functional imaging might detect early dysfunction in this region. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The prenatal development of some of the visual pathways in the cat

Lesions were made in the visual system in a series of cat fetuses of known gestational age, and fiber and terminal degeneration were stained by the Eager method. The times of development of the retinal projection, of the thalamcortical and corticothalamic projections of area 17 of the visual cortex, and of the intrinsic fibers in the visual cortex were examined. Enucleation of one eye resulted in degeneration being detected bilaterally in the lateral geniculate nuclei (LGN), superior colliculi (SC) and optic tracts. The optic nerves reached the optic chiasm by the thirtieth embryonic day (E30) and the optic tract connections with the LGN and SC were made by E37. The projection always appeared stronger in the contralateral LGN and SC, and the amount of degeneration increased in both sides with increasing age. A parasagittal knife cut was made in the dorsomedial crest of the visual cortex. Where the lesion passed through the cellular layers of the cortex, intrinsic fibers were cut when these were present. The deeper part of the incision through the white matter undercut the medial wall of the visual cortex, interrupting thalamocortical and corticothalamic fibers when these were present. The longer horizontal fibers that were intrinsic to the visual cortex began to develop during the last two weeks of gestation but were not fully developed at birth. In the undercut visual cortex distant from the place of entry of the lesion, and before the intrinsic fibers of the cortex had developed, degeneration was found in layers 1 and 4, demonstrating the presence of a thalamocortical pathway. The youngest fetus to show this degeneration was operated at E48. This degeneration was not present three days earlier at E45. Fiber plexuses that have been described earlier in development (Marin-Padilla, '71; Cragg, '75) do not appear to degenerate after undercutting the cortex. The corticothalamic pathway to the lateral posterior nucleus medial to the LGN was developed at E45. The descending pathways to the ipsilateral LGN and SC were developed by E48, but it is not known whether they are present before this. Thus degeneration has been used to detect the development of axonal pathways in the fetus for the first time; the major afferent and efferent pathways are developed at an earlier stage than has previously been described.     

Investigation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone for in vivo and iIn vitro murine embryopathy and embryonic ras mutations

The evoked potential recorded in the rat piriform cortex in response to electrical stimulation of the olfactory bulb is composed of an early component occasionally followed by a late component (60-70 ms). We previously showed that the late component occurrence was enhanced following an olfactory learning. In the present study carried out in naive rats, we investigated the precise conditions of induction of this late component, and its spatiotemporal distribution along the olfactory pathways. In the anaesthetized rat, a stimulating electrode was implanted in the olfactory bulb. Four recording electrodes were positioned, respectively, in the olfactory bulb, the anterior and posterior parts of the piriform cortex, and the entorhinal cortex. Simultaneous recording of signals evoked in the four sampled structures in response to stimulation of the olfactory bulb revealed that the late component was detected in anterior and posterior piriform cortex as well as in entorhinal cortex, but not in the olfactory bulb. The late component occurred reliably for a narrow range of low intensities of stimulation delivered at frequencies not exceeding 1 Hz. Comparison of late component amplitude and latency across the different recorded sites showed that this component appeared first and with the greatest amplitude in the posterior piriform cortex. In addition to showing a functional dissociation between anterior and posterior parts of the piriform cortex, these data suggest that the posterior piriform cortex could be the locus of generation of this late high amplitude synchronized activity, which would then propagate to the neighbouring regions.     

Beta-frequency (15-35 Hz) electroencephalogram activities elicited by toluene and electrical stimulation in the behaving rat

Bursts of beta-frequency (15-35 Hz) electroencephalogram activity occur in the olfactory system during odour sampling, but their mode of propagation within the olfactory system and potential contribution to the mechanisms of learning and memory are unclear. We have elicited large-amplitude beta activity in the rat olfactory system by applying noxious olfactory stimuli (toluene), and have monitored the bursts via chronically-implanted electrodes. Following exposure to toluene, coherent bursts with a peak frequency of 19.8 +/- 0.9 Hz were observed in the olfactory bulb, piriform cortex, entorhinal cortex and dentate gyrus. The timing of the bursts and the phases of electroencephalogram cross-spectra indicate that beta bursts propagate in a caudal direction from the olfactory bulb to the entorhinal cortex. The time delays between peaks of bursts in these structures were similar to latency differences for field potentials evoked by olfactory bulb or piriform cortex test-pulses. Peaks of burst cycles in the dentate region, however, were observed just prior to those in the entorhinal cortex. Surprisingly, power in toluene-induced beta-frequency oscillations was not increased following long-term potentiation induced by tetanic stimulation of the olfactory bulb, piriform cortex and entorhinal cortex. The activity of local inhibitory mechanisms may therefore counteract the effects of synaptic enhancements in afferent pathways during beta bursts. Low-frequency electrical stimulation of the piriform cortex was most effective in inducing coherent oscillatory responses in the entorhinal cortex and dentate gyrus at stimulation frequencies between 12 and 16 Hz. The results show that repetitive polysynaptic volleys at frequencies in the beta band induced by either toluene or electrical stimulation are transmitted readily within the olfactory system. The propagation of neural activity within this frequency range may therefore contribute to the transmission of olfactory signals to the hippocampal formation, particularly for those odours which induce high-amplitude bursts of beta activity.     

Distribution and developmental changes of adenylate kinase isozymes in the rat brain: localization of adenylate kinase 1 in the olfactory bulb

Changes in the levels of three adenylate kinase isozymes (AK1, AK2, and AK3) in the rat brain during development were investigated by immunoblot analysis. The levels of AK1 and AK3 of the whole brain increased after birth, while AK2 was detected only in the early embryonic period. In the adult rat brain, high levels of AK1 were present in the olfactory bulb. Immunohistochemical analysis showed that AK1 was found predominantly in the olfactory nerve layer and the glomerular layer. In the olfactory bulb, AK1 gene expression was enhanced in the early postnatal days, whereas it remained low in the cerebellum during the first 10 postnatal days. These results suggest that the AK isozymes are involved in neuronal maturation and regeneration. The understanding of the physiological actions of adenosine and ATP as neurotransmitters/neuromodulaters in the central nervous system has improved. ATP and adenosine receptors have been found to be widely distributed over the whole brain, although the intra- and extracellular metabolism of these compounds has not been well elucidated.     

Proliferation, migration and differentiation of neuronal progenitor cells in the adult mouse subventricular zone surgically separated from its olfactory bulb

The subventricular zone of the adult mammalian forebrain contains progenitor cells that, by migrating along a restricted pathway called the 'rostral migratory stream' (RMS), add new neurons to the olfactory bulb throughout life. To determine the influence of the olfactory bulb on the development of these progenitor cells, we performed lesions that interrupt this pathway and separate the olfactory bulb from the rest of the forebrain. By labelling cells born at several survival times after the lesions with the thymidine analogue bromodeoxyuridine (BrdU), we found that disconnection from the bulb influences the rate of BrdU incorporation by the progenitor cells. The number of labelled cells in lesioned mice was almost half that found in control mice. In the disconnected migratory pathway, the number of neurons expressing calretinin was increased indicating that neuronal differentiation was enhanced: newly born neurons occurred within and around the RMS, most of them expressed calretinin and left the pathway starting about 2 weeks after the lesion. Thereafter, these neurons preserving their phenotype, spread for long distances, and accumulated ectopically in dorsal regions of the anterior olfactory nucleus and the frontal cortex. Finally, transplantation of adult subventricular cells into the lesioned pathway showed that the lesion neither prevents neuronal migration nor alters its direction. Thus, although the olfactory bulb appears to regulate the pace of the developmental processes, its disconnection does not prevent the proliferation, migration and phenotypic acquisition of newly generated bulbar interneurons that, since they cannot reach their terminal domains, populate some precise regions of the lesioned adult forebrain.     

Hydroxylamine treatment increases glutathione-protein and protein-protein binding in human erythrocytes

Functional development of the rat whisker somatosensory system was studied by using the (14C) 2-deoxyglucose (2DG) metabolic mapping technique. Restrained rat pups had their left mystacial vibrissae stroked for 30 minutes and their brains harvested, sectioned, and autoradiographed from the level of the lower medulla to the frontal cortex. Subjects were tested at postnatal days (PNDs) 0-9 and 21. At birth, all subjects exhibited a significant increase of 2DG uptake in the left spinal trigeminal nuclei, the principal trigeminal sensory nucleus, and a portion of the right ventral posteromedial thalamic nucleus. The primary somatosensory cortex exhibited significant 2DG uptake contralateral to stimulation by PND 6, followed by the secondary somatosensory cortex at PND 7. The pattern of 2DG uptake in the somatosensory cortices became more intense and well defined by PND 9. Given that the somatosensory system develops in an orderly fashion from the periphery to higher brain structures, the present results show that brain structures mediating whisker sensory input are not metabolically active until projections from lower somatosensory centers are established. Neurons become responsive to whisker stimulation in the subcortical structures at birth and in the somatosensory cortex a few days later. This cortical activity follows the organization of the upper tier of thalamocortical fibers into a "barrelfield." Moreover, there is a gradual enhancement in functional activity of the vibrissa neurons at different somatosensory nuclei as rats mature. The present study elucidates the time course of functional development in the rat somatosensory system.     

An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons

Olfactory sensory neurons expressing a given odorant receptor project to two topographically fixed glomeruli in the olfactory bulb. We have examined the contribution of different cell types in the olfactory bulb to the establishment of this topographic map. Mice with a homozygous deficiency in Tbr-1 lack most projection neurons, whereas mice with a homozygous deficiency in Dlx-1 and Dlx-2 lack most GABAergic interneurons. Mice bearing a P2-IRES-tau-lacZ allele and deficient in either Tbr-1 or Dlx-1/Dlx-2 reveal the convergence of axons to one medial and one lateral site at positions analogous to those observed in wild-type mice. These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb.     

Deafferentation causes apoptosis in cortical sensory neurons in the adult rat

The present study provides an experimental model of the apoptotic death of pyramidal neurons in rat olfactory cortex after total bulbectomy. Terminal transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL), DNA electrophoresis, and neuronal ultrastructure were used to provide evidence of apoptosis; neurons in olfactory cortex were counted by stereology. Maximal TUNEL staining occurred in the piriform cortex between 18 and 26 hr postbulbectomy. Within the survival times used in the present study (up to 48 hr postlesion), cell death was observed exclusively in the piriform cortex; there was no evidence of cell death in any other areas connected with the olfactory bulb. Neurons undergoing apoptosis were pyramidal cells receiving inputs from, but not projecting to, the olfactory bulb. The apical dendrites of these neurons were contacted by large numbers of degenerating axonal terminals. Gel electrophoresis of DNA purified from lesioned olfactory cortex showed a ladder pattern of fragmentation. Inflammatory cells or phagocytes were absent in the environment of degenerating neurons in the early stages of the apoptotic process. The present model suggests that deafferentation injury in sensory systems can cause apoptosis. In addition, olfactory bulbectomy can be used for investigating molecular mechanisms that underlie apoptosis in mature mammalian cortical neurons and for evaluating strategies to prevent the degeneration of cortical neurons.     

Olfactory bulb development is altered in small-eye (Sey) mice

Small-eye (Sey) is a spontaneous, semidominant murine mutation that results from a point mutation in the Pax-6 gene. Both the eyes and the olfactory system fail to develop in homozygotes and these animals die neonatally. Heterozygotes (Sey/+) have different degrees of eye abnormalities including decreased lens size and cataracts. In the present study, we examined whether one mutated allele of Pax-6 also affects olfactory system development. By 42 days of age, main olfactory bulb volume was significantly decreased in Sey/+ animals compared with wild-type littermates, and this effect was even more dramatic in 70-day-old animals. In contrast, there was no effect on accessory olfactory bulb, olfactory epithelial, or vomeronasal organ development at any age in Sey/+ animals, demonstrating the specificity of the effect. In the main olfactory bulb, the largest differences in laminar volume were found in the glomerular and granule cell layers. These layers contain the olfactory bulb interneurons, and a subpopulation of these cells were found to be Pax-6 immunoreactive. Examination of the neurochemical consequences of this mutation showed that the number of both tyrosine hydroxylase (TH)- and gamma-aminobutyric acid (GABA)-immunoreactive profiles were dramatically decreased in Sey/+ animals as compared with controls. In contrast, neither calretinin nor calbindin immunoreactivity was affected by this mutation. Dual-labeling immunohistochemistry showed that nearly all TH-immunoreactive cells and a subpopulation of GABA-immunoreactive cells coexpressed Pax-6. However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive. These data indicate that two normal alleles of Pax-6 are required for normal olfactory bulb development and, as part of this effect, this gene may be involved in the development of specific neurotransmitter systems.     

Development of 5'-nucleotidase staining in the olfactory bulbs of normal and naris-occluded rats

The distribution of the adenosine-producing ecto-enzyme 5'-nucleotidase was investigated histochemically in the developing rat olfactory bulb. Rat pups underwent either unilateral surgical occlusion of the right external naris or sham surgery on postnatal day 1. At 10, 20, or 30 days postpartum, horizontal sections of the olfactory bulb were reacted histochemically to reveal the locus and intensity of 5'-nucleotidase activity. Relative staining levels were determined by optical densitometry in standardized bulb regions. A marked, age-related increase in staining density was observed. Reaction product was found primarily in neuropil areas. The P10 and P20 control animals did not exhibit right/left differences in bulb staining; however, some laterality was observed in P30 animals. Inter-glomerular and regional variations were observed throughout the developmental period, including (1) differences between neighboring glomeruli; (2) a gradient in the dorsal-ventral axis of the bulb; and (3) a higher staining density in the medial-caudal portion of the bulb. In subjects with occluded nares, asymmetries in right/left bulb 5'-nucleotidase staining patterns were detected throughout development. Bulbs ipsilateral to the blocked nares exhibited increased staining density, suggesting that the procedure enhanced enzymatic activity. Understanding these variations in 5'-nucleotidase staining may be important for a complete understanding of the mechanisms of olfactory bulb maturation and may give insight into the possible role of this enzyme in synaptic malleability during nervous system development and regeneration.     

Protein synthesis inhibitors delay transneuronal death in the piriform cortex of young adult rats

It has been demonstrated that apoptotic cell death is an active process that is dependent on RNA and protein synthesis. The question remains as to whether neuronal death in adult, mammalian brains can also be demonstrated in vivo to be dependent on protein synthesis. To address this question we have analysed transneuronal death in the piriform (olfactory) cortex. Following unilateral olfactory bulb ablation in young adult rats, layer IIa of the piriform cortex undergoes rapid degeneration, that commences 12 h after ablation and that is almost complete at 48 h. In order to block protein synthesis, three to six subcutaneous injections of the short acting protein synthesis inhibitor anisomycin, were given at 2 h intervals beginning just before the ablation of the olfactory bulb. In other cases a single injection of the long acting protein synthesis inhibitor emetine were made intracerebrally just before or after olfactory bulb ablation. The number of dying cells was then counted in sections through the rostrocaudal extent of the piriform cortex. Both anisomycin and emetine injections markedly reduced the number of pyknotic cells in layer IIa of the piriform cortex after olfactory bulb ablation. The effect of anisomycin was dose-dependent, near lethal doses leading to an almost complete absence of cell death (six injections of 100 mg/kg). As the doses of anisomycin were reduced, more dying cells were observed. Emetine was only effective at near lethal doses (10 mg/kg) and showed a greater capacity to reduce the levels of cell death when injected into structures near the piriform cortex (e.g., accumbens nucleus) than when injected into more distant structures. To further confirm that the cell death observed was due to apoptosis, we analysed sections by tunel staining to demonstrate DNA fragmentation. We found that tunel-positive cells were also always pyknotic, one of the landmarks of apoptosis. The appearance of pyknotic cells labelled by the tunel method demonstrated that the dying cells in the piriform cortex did indeed undergo apoptosis.     

Oncoprotein v-Myb and retinoic acid receptor alpha are mutual antagonists

The expression of nitric oxide synthase (NOS) in the olfactory bulb was compared between two mouse strains, CD-1 and BALB/c, that differ in the connectivity within their olfactory glomeruli, their content of tyrosine hydroxylase, and their response to olfactory deafferentation. Labelled cells were qualitatively and quantitatively analyzed by both immunohistochemistry for NOS and histochemistry for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (ND). Both periglomerular cells and short-axon cells were observed with both techniques employed, and their colocalization in the same neurons demonstrated that ND is a reliable marker for NOS-expressing cells in the mouse olfactory bulb (OB). The histochemical technique differentiates two types of glomeruli: ND-positive and ND-negative. Olfactory glomeruli in the CD-1 strain were about 7% larger than those in the BALB/c animals. While the density of NOS/ND-containing periglomerular cells was similar between both strains studied, more NOS/ND-labelled cells were observed in the ND-positive glomeruli (P = 0.002). Since periglomerular cells in the BALB/c strain do not receive direct olfactory receptors synapses, the present results indicate that such inputs do not regulate the expression of NOS and ND activity in the periglomerular cells. The different densities of NOS/ND-expressing periglomerular cells may indicate that nitric oxide is implicated in a differential modulation of the odor response within both types of chemically distinct glomeruli in the mouse olfactory bulb.     

Selective neuronal expression of green fluorescent protein with cytomegalovirus promoter reveals entire neuronal arbor in transgenic mice

In simple nervous systems, identified groups of neurons can be studied in depth. To allow the same advantage in the mammalian brain, we have generated green fluorescent protein (GFP) transgenic mice in which only a few types of neurons are strongly labeled with a fluorescent molecule, which the neurons synthesize internally, allowing the cells, their dendrites, filopodia, and axons to be identified in both living and fixed CNS, in slices and culture. The same neurons, with GFP expression controlled by part of the major immediate early promoter of human cytomegalovirus (CMV), show GFP beginning early in development, from one generation to the next, allowing cellular and physiological studies of axonal and dendritic growth, fate mapping, anatomical connections, and synapse formation in identified neurons. The human CMV promoter sequence we used was different from that used in previous work with other reporter genes and gave a dramatically different pattern of expression. Two transgenic lines with the same CMV promoter show similar anatomical patterns of expression in the present study. Strong GFP labeling was found in a subpopulation of mossy fibers that innervated parasagittal bands in the cerebellar cortex and olfactory axons that projected into the olfactory bulb, subsets of motoneurons and dorsal root ganglion cells, granule but not mitral cells of the olfactory bulb, and a group of neurons in the hypothalamic suprachiasmatic nucleus. A novel type of neuron was strongly labeled in the olfactory bulb external plexiform layer. In normal brains, CMV does not constitute a threat, but in the developing brain, CMV can cause debilitating neurodegeneration and death; studies using the CMV promoter aid in understanding the affinity of CMV that has been suggested for specific brain regions.     

Afferent and efferent connections of the nucleus sphericus in the snake Thamnophis sirtalis: convergence of olfactory and vomeronasal information in the lateral cortex and the amygdala

This paper is an account of the afferent and efferent projections of the nucleus sphericus (NS), which is the major secondary vomeronasal structure in the brain of the snake Thamnophis sirtalis. There are four major efferent pathways from the NS: 1) a bilateral projection that courses, surrounding the accessory olfactory tract, and innervates several amygdaloid nuclei (nucleus of the accessory olfactory tract, dorsolateral amygdala, external amygdala, and ventral anterior amygdala), the rostral parts of the dorsal and lateral cortices, and the accessory olfactory bulb; 2) a bilateral projection that courses through the medial forebrain bundle and innervates the olfactostriatum (rostral and ventral striatum); 3) a commissural projection that courses through the anterior commissure and innervates mainly the contralateral NS; and 4) a meager bilateral projection to the lateral hypothalamus. On the other hand, important afferent projections to the NS arise solely in the accessory olfactory bulb, the nucleus of the accessory olfactory tract, and the contralateral NS. This pattern of connections has three important implications: first, the lateral cortex probably integrates olfactory and vomeronasal information. Second, because the NS projection to the hypothalamus is meager and does not reach the ventromedial hypothalamic nucleus, vomeronasal information from the NS is not relayed directly to that nucleus, as previously reported. Finally, a structure located in the rostral and ventral telencephalon, the olfactostriatum, stands as the major tertiary vomeronasal center in the snake brain. These three conclusions change to an important extent our previous picture of how vomeronasal information is processed in the brain of reptiles.     

MR cholangiography in children after liver transplantation from living related donors

A highly specific anti-glutamate monoclonal antibody, mAb2D7, was used together with light and electron microscopy to elucidate the role played by the amino acid glutamate in the projection from the olfactory bulb to the piriform cortex in the rat. By light microscopy, glutamate-like immunoreactivity was observed in neuronal cell bodies and in the neuropil of the piriform cortex. Double labelling experiments which involved injections of wheat germ agglutinin-horse--radish peroxidase into the olfactory bulb and a post-embedding immunogold method for electron microscopy revealed anterogradely labelled terminals making asymmetric synaptic contacts on dendrites in the piriform cortex which contained high levels of glutamate as assessed by quantification. These results further support a role for glutamate as a neurotransmitter in the efferent pathway of the rat olfactory bulb.     

Changes in electrical activity of rabbit olfactory bulb and cortex to conditioned odor stimulation.

Rabbits with chronically implanted electrodes in olfactory bulb and cortex were classically conditioned to give an increase in relative frequency of sniffing to odor stimuli (CS+) reinforced with mild electric shock. Electroencephalographic high-frequency (35–85 Hz) bursts were recorded from an ensemble of nine bulbar depth electrodes and a second ensemble of 50 cortical surface electrodes. The olfactory cortex responded to the CS+ with sustained elevation of burst amplitude even though the olfactory bulb, from which it receives its primary centripetal input, underwent a marked decline in burst amplitude during the same time period. The amplitude reduction was not spatially uniform: The burst of the bulbar region that declined most in amplitude had the greatest phase lag with respect to the bulbar ensemble average burst. These effects were learning related because they did not occur for CS+ trials at the beginning of conditioning or for unreinforced control trials at any time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopaminergic modulation of olfactory bulb processing affects odor discrimination learning in rats.

Olfactory behavioral studies have shown that, when modulated through systemic injections, D1 and D2 receptors have opposing effects on odor discrimination learning. In the present study, cannulated male Sprague–Dawley rats were used to investigate how the modulation of these 2 types of dopaminergic receptors through direct infusion of D1/D2 agonists and antagonists into the olfactory bulb affect olfactory perception. Dopaminergic modulation was locally altered by manipulations of D1 (agonist SKF 82958: 14.6, 43.8, & 143.6 mM; antagonist SCH-23390: 13.4, 40.1, & 60.1 mM) and D2 (agonists quinpirole: 78.2, 117.3, & 156.4 mM; antagonist sulpiride: 0.3, 0.9, & 2.9 mM) receptors during a simultaneous odor discrimination task. The authors found that modulation of D2, but not D1, receptors significantly affected rats’ odor discrimination performance. A significant positive correlation between blockade of D2 receptors and discrimination performance, as well as a significant negative correlation between D2 receptor activation and discrimination performance, was observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory bulb glycogen metabolism: noradrenergic modulation in the young rat

The olfactory bulb exhibits high glycogen phosphorylase activity, the rate-limiting enzyme in the mobilization of glycogen. The bulb also receives dense noradrenergic innervation and noradrenaline is known to stimulate glycogen breakdown. We determined the levels of glycogen in the bulb over the course of development and then determined the ability of noradrenaline to mobilize bulb glycogen. At birth, olfactory bulbs have very high levels of glycogen, with levels declining as the pups develop. Picomolar levels of noradrenaline mobilize glycogen in the bulb,. Initially, beta-adrenergic receptors mediate teh glycogenolysis and subsequently, the alpha-noradrenergic receptors in the bulb stimulate the breakdown of glycogen. Carnosine is involved in the repletion of bulb glycogen levels. The stimulation of glycogen breakdown by noradrenaline may play a role in allowing the increased activity that accompanies early olfactory stimulation.