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[A 75-year-old woman with multiple cranial nerve palsies and a paranasal mass].

We report a 75-year-old woman with multiple cranial nerve palsies. The patient was well until January, 1992 when she had an onset of deafness in her left ear; she developed left facial pain in September, 1992, and came to the ENT clinic of our Izunagaoka Juntendo Hospital. She had chronic sinusitis; she was referred to neurology clinic on September 25 because of decrease in the superficial sensation in the second division of the left trigeminal nerve. She developed blurring of her left vision, and was admitted to the neurology service of Juntendo Izunagaoka Hospital on December 7th, 1992. On admission, general physical examination was unremarkable. Neurologic examination revealed alert and mentally sound woman; higher cerebral functions were intact. In the cranial nerves, olfactory sensation was normal; the left vision was reduced to discriminate light and dark; the right vision was normal. Pupils were round and isocoric, but the light reflex was sluggish on the left side; the abduction of the left eye was impossible; other ocular muscles appeared intact. Sensation of the left face was almost completely lost; the corneal reflex was lost on the left side; no jaw deviation was noted. She had near complete left facial palsy of the peripheral type; the left ear was deaf. The movement of the left soft palate was slightly weak, but no deviation of the uvula was noted; she had no dysarthria or dysphagia.2/

Aged↗

Glucose-6-phosphate dehydrogenase and NADPH-consuming enzymes in the rat olfactory bulb.

The resistance to oxidative stress is a multifactorial reaction involving the clustering of transcriptionally regulated genes. Because glucose-6-phosphate dehydrogenase (G6PD), the principal enzyme responsible for reducing power, is highly expressed in the olfactory bulb (OB), it is of interest to verify whether other enzymes utilizing NADPH are also highly expressed. The level and localization of G6PD- and NADPH-consuming enzymes, such as NADPH-cytochrome P450 oxidoreductase (P450R), glutathione reductase (GR), and NADPH-diaphorase (NADPH-d), were analyzed in the rat olfactory bulb (OB) by quantitative histochemistry and immunohistochemistry. The highest concentration of G6PD, P450R, and GR was observed in the olfactory nerve layer (ONL), suggesting a correlation in the expression of these enzymes at the gene level. Correlation in staining intensity between G6PD and NADPH-d activities occurred only in part of the ONL, some glomeruli, and scattered periglomerular cells. This peculiar distribution of NADPH-d could reflect a spatial patterning of the nose to bulb projections. Taken together, these results indicate that G6PD expression in the ONL could be related to the importance of generating a substantial supply of NADPH to sustain the detoxifying systems represented by GR and P450R reactions and, only in discrete zones, by NADPH-d activity.

Animals↗

High-resolution 2-deoxyglucose autoradiography in quick-frozen slabs of neonatal rat olfactory bulb.

We have used rapid freezing and freeze-substitution fixation to permit electron microscopic study of [3H]2-deoxyglucose autoradiographs. The techniques minimize diffusion of label into processing fluids and, by inference, migration of label within tissue. Slabs of olfactory bulbs from 12-day-old rats were quick-frozen after one hour of exposure to physiological olfactory stimuli. In light microscopic autoradiographs at low magnification, the neuropil of individual olfactory glomeruli appeared uniformly labeled with different levels of labeling in different glomeruli. At higher magnification, glomerular neuropil labeling consisted of small unlabeled regions surrounded by label clusters, suggesting greater deoxyglucose uptake by olfactory nerve terminals as compared with their postsynaptic dendrites. Periglomerular neurons were labeled differentially. Some microglia and glia precursor cells were heavily labeled in all bulbar laminae. The ultrastructure of cells and neuropil in all bulbar laminae was well-preserved. Cell processes and organelles could be identified in both stained sections and unstained electron microscopic autoradiographs. These experiments demonstrate the feasibility of combining quick-freezing with freeze substitution, in order to extend the resolution of studies using diffusable tracers such as 2-deoxyglucose. The results suggest that this is a promising method for assessing several controversies concerning deoxyglucose incorporation and neuronal and glial metabolism.

Animals↗

[Psychopathology and neuro-ophthalmology in meningioma of the olfactory groove].

In 14 patients with a surgically nad histopathologically verified meningioma of the olfactory nerve groove (OGM) (12 women, 2 men), clinical findings and diagnosis were analysed, especially with respect to neuropathology and psychopathology. The apodictic theorem that an OGM leads to a Foster-Kennedy syndrome as well as to a psychopathological orbital brain syndrome cannot be maintained. The Foster-Kennedy syndrome does not occur in a characteristically high incidence, and psychopathologically an orbital brain syndrome can only be diagnosed in case of an anterior location of the OGM. The more the OGM shows starting point or growth development to or from the anterior chiasmal angle, the more is resembles that psychopathological syndrome that we have found and described for the meningioma of the Tuberculus sellae.

Brain Neoplasms↗

Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI.

Dynamic blood oxygenation level-dependent functional MRI was applied at 7 T in the rat olfactory bulb (OB) with pulsed delivery of iso-amyl acetate (IAA) and limonene. Acquisition times for single-slice and whole OB data were 8 and 32 s, respectively, with spatial resolution of 220 x 220 x 250 micrometer. On an intrasubject basis, short IAA exposures of 0.6 min separated by 3.5-min intervals induced reproducible spatial activity patterns (SAPs) in the olfactory nerve layer, glomerular layer, and external plexiform layer. During long exposures ( approximately 10 min), the initially dominant dorsal SAPs declined in intensity and area, whereas in some OB regions, the initially weak ventral/lateral SAPs increased first and then decreased. The SAPs of different concentrations were topologically similar, which implies that whereas an odor at various concentrations activates the same subsets of receptor cells, different concentrations are assessed and discriminated by variable magnitudes of laminarspecific activations. IAA and limonene reproducibly activated different subsets of receptor cells with some overlaps. Whereas qualitative topographical agreement was observed with results from other methods, the current dynamic blood oxygenation level-dependent functional MRI results can provide quantitative SAPs of the entire OB.

Animals↗

Soluble guanylyl cyclase appears in a specific subset of periglomerular cells in the olfactory bulb.

In the brain, nitric oxide acts as an atypical messenger in cellular nonsynaptic transmission. In the olfactory bulb, this gas is produced at the level of the olfactory glomeruli by a subpopulation of periglomerular cells that participates in the first synaptic relay of the olfactory information between the olfactory nerve and the dendritic tufts of principal cells. It has been proposed that nitric oxide modulates intraglomerular synaptic integration of sensory inputs, but its specific role in the glomerular circuitry remains to be understood. In this article, we demonstrate that, in the glomerular circuits, a specific subset of periglomerular cells, most of them expressing the calcium binding protein calbindin D-28 k, expresses the beta1 subunit of the soluble guanylyl cyclase. These cells could be the targets for the action of nitric oxide at the glomerular level via activation of soluble guanylyl cyclase and production of cGMP.

Animals↗

AMPA/kainate receptors drive rapid output and precise synchrony in olfactory bulb granule cells.

Gamma frequency (30-70 Hz) synchronized oscillatory activity in the olfactory bulb is widely believed to be important for odor detection and discrimination. As in other circuits with "gamma activity," the activity in the bulb is driven by GABAergic interneurons, specifically a class of axonless cells called granule cells. However, bulb granule cells appear to lack some key mechanistic features that promote rapid synchrony in other circuits, including direct electrical interconnections and dominant actions for fast neurotransmitter receptors. At least under "static" stimulus conditions, granule cells are driven by kinetically slow NMDA receptors. Here, I used patch-clamp recordings in rat olfactory bulb slices to better understand mechanisms that shape granule cell activity under "dynamic" stimulus conditions that mimic a natural odor stimulus. During a 4 Hz patterned stimulation of olfactory nerve afferents, activation of single granule cells was primarily controlled by two classes of AMPA/kainate receptor-mediated synaptic inputs derived from output mitral cells. The rapid kinetics of these receptors, together with inactivation of A-type potassium channels, ensured that granule cells had short spike-response times. Studies in cell pairs, moreover, indicated that excitatory inputs could synchronize granule cells on a rapid time scale (2-5 ms), in turn resulting in phase-locked GABA release onto mitral cells. The precision of granule cell synchrony was controlled by the same biophysical mechanisms that promoted rapid single-cell spiking. These studies demonstrate the mechanistic underpinnings that transform a circuit with slow, uncoupled activity under static conditions into a fast, dynamic circuit operating with high precision under physiological conditions.

Action Potentials↗

Immunohistochemical localization of glutamate in the gerbil main olfactory bulb using an antiserum directed against glutamate.

Information on the localization and the roles of glutamate in the nervous system is becoming valuable because the axon terminals of the olfactory sensory neurons and the synapses of the mitral and tufted output cells appear to be glutamatergic. In this study, we have analysed the distribution of glutamate immunoreactivity in the main olfactory bulb (MOB) of the Mongolian gerbil using an antiserum directed against glutamate. Glutamate immunoreactivity in the MOB was present in the olfactory nerve layer (Onl), glomerular layer (GL), external plexiform layer (EPL) and mitral cell layer (ML), but not in the granule cell layer (GCL). Glutamate immunoreactivity detected in the Onl was thought to be terminal ramifications of glomeruli. Some neurons in the periglomerular region showed glutamate immunoreactivity. In the EPL, glutamate immunoreactivity was found in some neuronal somata (tufted cells) and processes. In addition, mitral cells in the ML were labelled by the glutamate antibody. The pattern of glutamate immunoreactivity in the mitral cells was similar to that in the tufted cells. In brief, glutamate in the gerbil MOB is the neurotransmitter used by primary afferents and output neurons.

Animals↗

Embryonic development of the gonadotropin-releasing hormone (GnRH) system in the chick: a spatio-temporal analysis of GnRH neuronal generation, site of origin, and migration.

We present a quantitative immunocytochemical study of GnRH migration by developmental stage. GnRH peptide was detected in cells of the olfactory epithelium at stage 19. Migration was initiated a few hours later at stage 20. Of interest is the observation that GnRH neurons paused at the central nervous system border for 3 days, entering the brain at stage 29. The major expansions of the GnRH population occurred at two points; stages 26 and 42. In one animal a third population expansion occurred after hatching, with the number of GnRH cells reaching 6600. To determine the site of origin of GnRH cells, embryos were exposed to tritiated thymidine and killed 5 h later. Most GnRH cells incorporated label in the olfactory epithelium; however, some autoradiographically labeled GnRH cells, possessing a neuronal morphology, were found in the olfactory nerve and the forebrain, suggesting that some GnRH neurons divide as they migrate. A cumulative labeling method employing tritiated thymidine was used to examine the birth date of GnRH neurons. Postmitotic GnRH cells were first detected at stages 19-21. At stage 24, a peak in GnRH neurogenesis preceded the increase in GnRH neurons expressing their peptide at stage 26. After stage 24, there was a gradual addition of postmitotic cells to the population through stage 35. A pulse-chase paradigm indicated that birth date did not influence the final GnRH cell distribution. Injections at stage 29, when 10% of the GnRH neurons are born, generated double labeled cells in all locations where placode-derived GnRH neurons reside.

Animals↗

Inverse expression of olfactory cell adhesion molecule in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat main olfactory bulb.

The projection of olfactory sensory neuron (OSN) axons from the olfactory epithelium (OE) to the olfactory bulb (OB) is highly organized but topographically complex. Evidence suggests that odorant receptor expression zones in the OE map to the OB about orthogonal axes. One candidate molecule for the formation of zone-specific targeting of OSN axon synapses onto the OB is the olfactory cell adhesion molecule (OCAM). OCAM(+) OSNs are restricted to three of the four zones in the OE and project their axons to the ventral OB where they form synapses with mitral/tufted (M/T) cells. To determine when this zonal connection is established, we have examined OCAM expression in rat olfactory system, during seminal periods of glomerular formation. OCAM(+) axons sort out in the ventral olfactory nerve layer of the OB before glomerular formation. Surprisingly, OCAM was also expressed transiently by subsets of M/T cell dendrites located in the dorsal OB. The expression of OCAM by OSN axons and M/T dendrites was asymmetrical; in the dorsal OB, OCAM(-) OSN axons synapsed on OCAM(+) M/T dendrites, whereas in the ventral OB, OCAM(+) OSN axons synapsed on OCAM(-) M/T dendrites. The restricted spatial map of OCAM(+) M/T cells appeared earlier in development than the zonal segregation of OCAM(+) OSN axons. Thus, OCAM on M/T cell dendrites may act in a spatiotemporal window to specify regions of the developing rat OB, thereby establishing a foundation for mapping of the OE zonal organization onto the OB.

Animals↗

Evidence for Ca(2+)-permeable AMPA receptors in the olfactory bulb.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), a subtype of glutamate receptor, contribute to olfactory processing in the olfactory bulb (OB). These ion channels consist of various combinations of the subunits GluR1-GluR4, which bestow certain properties. For example, AMPARs that lack GluR2 are highly permeable to Ca(2+) and generate inwardly rectifying currents. Because increased intracellular Ca(2+) could trigger a host of Ca(2+)-dependent odor-encoding processes, we used whole cell recording as well as histological and immunocytochemical (ICC) techniques to investigate whether AMPARs on rat OB neurons flux Ca(2+). Application of 1-naphthylacetyl spermine (NAS), a selective antagonist of Ca(2+)-permeable AMPARs (CP-AMPARs), inhibited AMPAR-mediated currents in subsets of interneurons and principal cells in cultures and slices. The addition of spermine to the electrode yielded inwardly rectifying current-voltage plots in some cells. In OB slices, olfactory nerve stimulation elicited excitatory responses in juxtaglomerular and mitral cells. Bath application of NAS with d,l-2-amino-5-phosphonovaleric acid (AP5) to isolate AMPARs suppressed the amplitudes of these synaptic responses compared with responses obtained using AP5 alone. Co(2+) staining, which involves the kainate-stimulated influx of Co(2+) through CP-AMPARs, produced diverse patterns of labeling in cultures and slices as did ICC techniques used with a GluR2-selective antibody. These results suggest that subsets of OB neurons express CP-AMPARs, including functional CP-AMPARs at synapses. Ca(2+) entry into cells via these receptors could influence odor encoding by modulating K(+) channels, N-methyl-d-aspartate receptors, and Ca(2+)-binding proteins, or it could facilitate synaptic vesicle fusion.

Animals↗

Synaptic organization in the teleost olfactory bulb.

Some aspects of the synaptic organization in the olfactory bulb of the goldfish were investigated morphologically by light and high voltage electron microscopy of Golgi-impregnated material, combined Golgi-electron microscopy and electron microscopy of the serial thin sections. In this paper we have analyzed two particular synaptic areas in the glomerular layer (and the superficial part of the plexiform layer), that is, the glomerular area and the nest (N), and five types of neurons participating in these two areas. The glomerular area consists mainly of olfactory nerve terminals (ON), mitral cell dendrites (M), and granule cell dendrites (G), which make a fundamental synaptic pattern in this area; ON leads to M in equilibrium G. In addition to these three elements, there are some other types of neuronal processes in the glomerular area. One is the ruffed cell dendrite (r), which frequently gives rise to glial sheet-like appendages coiling around and covering the mitral cell dendrites. Another is a type of thin cylindrical dendritic processes, which occasionally makes mixed synapses with the mitral cell dendrites, thus named here the dendrites of "the mixed-synapse cell". Another particular synaptic area, the nest, is around the initial unmyelinated portion of the axon (IP) of the ruffed cell, which has many protrusions on its IP. The nest consists mainly on the protrusions of the ruffed cell IP (R), the granule cell dendrites (G) and the perinest cell dendrites (PN). R make synapses with G very similar to those between M and G in the glomerular area. The basic synaptic pattern in the nest is R in equilibrium G leads to PN. The correlation between electron microscopically characterized neuronal processes and light microscopically observed cell types was attempted by serial thin sectioning-reconstruction studies and combined Golgi-electron microscopy studies. A part of the neuronal local circuit in the teleost olfactory bulb was described and compared to that in the mammalian olfactory bulb.

Animals↗

Odour-evoked [Ca2+] transients in mitral cell dendrites of frog olfactory glomeruli.

We measured Ca2+ concentration, [Ca2+], transients in mitral cell distal apical dendritic tufts produced by physiological odour stimulation of the olfactory epithelium and electrical stimulation of the olfactory nerve (ON) using two-photon scanning and conventional wide-field microscopy of Ca2+-Green-1 dextran in an in vitro frog nose-brain preparation. Weak or strong ON shock-evoked fluorescence transients always had short latency with an onset 0-10 ms after the onset of the bulb local field potential, rapidly increasing to a peak of up to 25% fractional fluorescence change (DeltaF/F) in 10-30 ms, were blocked by 10 microM CNQX, decaying with a time constant of about 1 s. With stronger ON shocks that activated many receptor axons, an additional, delayed, sustained AP5-sensitive component (peak at approximately 0.5 s, up to 40% DeltaF/F maximum) could usually be produced. Odour-evoked [Ca2+] transients sometimes displayed a rapid onset phase that peaked within 50 ms but always had a sustained phase that peaked 0.5-1.5 s after onset, regardless of the strength of the odour or the amplitude of the response. These were considerably larger (up to 150% DeltaF/F) than those evoked by ON shock. Odour-evoked [Ca2+] transients were also distinguished from ON shock-evoked transients by tufts in different glomeruli responding with different delays (time to onset differed by up to 1.5 s between different tufts for the same odour). Odour-evoked [Ca2+] transients were increased by AMPA-kainate receptor blockade, but substantially blocked by AP5. Electrical stimulation of the lateral olfactory tract (5-6 stimuli at 10 Hz) that evoked granule cell feedback inhibition, blocked 60-100% of the odour-evoked [Ca2+] transient in tufts when delivered within about 0.5 s of the odour. LOT-mediated inhibition was blocked by 10 microM bicuculline.

Animals↗

PET shows that odors are processed both ipsilaterally and contralaterally to the stimulated nostril.

The olfactory nerve is the only cranial nerve with established ipsilateral primary cerebral anatomical projections. Whether these projections correspond to the functional pathways for monorhinal processing of odor perception is, however, unknown. We therefore studied cerebral blood flow (rCBF) with [15O]butanol-PET in 18 healthy females during monorhinal smelling of single odors (OS) and odorless air (AS). Compared with AS, OS activated right amygdala and piriform cortex (confluent cluster), right orbitofrontal cortex, left insula, right thalamus, and anterior cingulate. A post hoc analysis showed that the first three regions were activated independently of the stimulated side, but that right orbitofrontal rCBF was higher during the right nostril stimulations. Left insula was activated mainly by the right nostril stimuli, and right thalamus by the left nostril stimuli. Odors seem to be processed both ipsi and contralaterally, with a right hemisphere preponderance irrespective of the stimulated nostril.

Adult↗

Morphological relations between the receptor neurons, sustentacular cells and Schwann cells in the olfactory mucosa of the salamander.

The morphological characteristics of olfactory receptor neurons and their relations to the sustentacular cells and to the sheath cells of Schwann in the olfactory mucosa of the salamander (Ambystoma maculatum et tigrinum) were studied using a modification of the rapid Golgi technique. The bipolar receptor neurons had a fusiform-shaped cell body whose apical pole gave rise to a surface-reaching dendrite and a basal pole which gave rise to an axon. The length and width of the dendrite, although variable, were positively correlated with the relative depth at which the cell body was located in the sensory epithelium. Beyond the initial segment, the axon had a sinuous course prior to its entrance into the lamina propria. Within the lamina propria, the axons were associated with the sheath cells of Schwann to form the olfactory nerve fascicles. The processes of adjacent sheath cells formed an elaborate network of continuous cavities through which the axons coursed. Two morphologically distinct varieties of sustentacular cells, designated types I and II, were found in the sensory epithelium. Both types had a columnar profile consisting of an elongated cell body, a central stalk, and a basilar expansion of the stalk found at the junction of the epithelium with the lamina propria. The central stalk of type I sustentacular cells was unbranched, whereas that of type II cells gave rise to riblike processes from which cytoplasmic veils extended to envelop the cell bodies of receptor neurons. The basilar expansions were found in close apposition to the wall of capillaries or to acinar cells of Bowman's glands located in the most superficial region of the lamina propria. The morphological relationships and possible interdependencies among receptor neurons, the types of sustentacular cells, and the sheath cells are discussed.

Animals↗

Human responses to propionic acid. I. Quantification of within- and between-participant variation in perception by normosmics and anosmics.

The objective of this study was to fully characterize normosmic perception of stimuli expected to cause widely varying degrees of olfactory and nasal trigeminal stimulation and to directly evaluate the possible role of olfactory nerve stimulation in nasal irritation sensitivity. During each of four identical test sessions, four anosmic and 31 normosmic participants were presented with a range of concentrations extending from peri-threshold for normosmics to supra-threshold for anosmics. For each session, odor (O) and nasal irritation (NI) sensitivities were summarized in terms of the concentrations required to produce four sensation levels ('iso-response' concentrations). Within-participant variation in these iso-response concentrations was < 10-fold for 95% of normosmics, for both O and NI. For O but not NI, these apparent fluctuations in sensitivity were largely accounted for by the uncertainty surrounding the iso-response concentrations calculated for each session. Anosmics exhibited minimal within- and between-participant variation in NI and required, for all but the highest perceptual level, a higher concentration than almost all normosmics. Between-participant variation, expressed in terms of 90% confidence interval widths, was approximately 0.5 log units for both O and NI for the highest perceptual level, but increased to approximately 0.8 and 1.8 log units, respectively, for the lowest (peri-threshold) level. Our findings suggest that: (i) most apparent variation over time in O sensitivity is actually a reflection of the uncertainty surrounding estimates of sensitivity obtained for each session; (ii) within- and between-participant variation in O sensitivity is far less than is commonly reported; and (iii) low to moderate levels of NI in normosmics are the result of relatively weak trigeminal stimulation combined with much greater olfactory activation.

Adolescent↗

Olfactory bulb external tufted cells are synchronized by multiple intraglomerular mechanisms.

In rat olfactory bulb slices, external tufted (ET) cells spontaneously generate spike bursts. Only ET cells affiliated with the same glomerulus exhibit significant synchronous activity, suggesting that synchrony results mainly from intraglomerular interactions. The intraglomerular mechanisms underlying their synchrony are unknown. Using dual extracellular and patch-clamp recordings from ET cell pairs of the same glomerulus, we found that the bursting of ET cells is synchronized by several mechanisms. First, ET cell pairs of the same glomerulus receive spontaneous synchronous fast excitatory synaptic input that can also be evoked by olfactory nerve stimulation. Second, they exhibit correlated spontaneous slow excitatory synaptic currents that can also be evoked by stimulation of the external plexiform layer. These slow currents may reflect the repetitive release of glutamate via spillover from the dendritic tufts of other ET or mitral/tufted cells affiliated with the same glomerulus. Third, ET cells exhibit correlated bursts of inhibitory synaptic activity immediately after the synchronous fast excitatory input. These bursts of IPSCs were eliminated by CNQX and may therefore reflect correlated feedback inhibition from periglomerular cells that are driven by ET cell spike bursts. Fourth, in the presence of fast synaptic blockers, ET cell pairs exhibit synchronous slow membrane current oscillations associated with rhythmic spikelets, which were sensitive to the gap junction blocker carbenoxolone. These findings suggest that coordinated synaptic transmission and gap junction coupling synchronize the spontaneous bursting of ET cells of the same glomerulus.

Animals↗

Long-lasting depolarizations in mitral cells of the rat olfactory bulb.

We investigated the mechanisms of long-lasting depolarizing potentials (LLDs) generated in mitral cells with whole-cell patch recordings in the rat olfactory bulb slice. LLDs occur spontaneously and are evoked by either orthodromic stimulation of the olfactory nerve or antidromic stimulation of mitral and tufted (M/T) cells. LLDs are followed by a long refractory period, limiting LLD generation to approximately 1 Hz. LLD production does not appear to involve either intrinsic voltage-activated or metabotropic mechanisms. The initiation of LLDs requires activation of non-NMDA but not NMDA receptors. Dual recordings from the apical dendrites and somata of mitral cells show that LLDs are generated in the distal portion of the apical dendrite, most likely in the glomerulus. The rising phase of LLDs shows characteristics of polyneuronal input, including a high variability and sensitivity to charge screening. Paired recordings from adjacent mitral cells suggest that LLDs occur synchronously only in cells whose apical dendrites ramify in the same glomerulus. These findings suggest that LLDs involve recurrent, intraglomerular dendrodendritic interactions among M/T cells.

2-Amino-5-phosphonovalerate↗