Abstract: In the mammalian forebrain, most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles, including a discrete area of the subventricular zone (SVZ). In this region, neurogenesis continues into adulthood. Most of the cells generated in the SVZ are neuronal precursors with progeny that migrate rostrally along a pathway known as the rostral migratory stream before they reach the main olfactory bulb (MOB) where they differentiate into local interneurons. The olfactory system thus provides an attractive model to investigate neuronal production and survival, processes involving interplay between genetic and epigenetic influences. The present study was conducted to investigate whether exposure to an odor-enriched environment affects neurogenesis and learning in adult mice. Animals housed in either a standard or an odor-enriched environment for 40 d were injected intraperitoneally with bromodeoxyuridine (BrdU) to detect proliferation among progenitor cells and to follow their survival in the MOB. The number of BrdU-labeled neurons was not altered 4 hr after a single BrdU injection. In contrast, the number of surviving progenitors 3 weeks after BrdU injection was markedly increased in animals housed in an enriched environment. This effect was specific because enriched odor exposure did not influence hippocampal neurogenesis. Finally, we showed that adult mice housed in odor-enriched cages display improved olfactory memory without a change in spatial learning performance. By maintaining a constitutive turnover of granule cells subjected to modulation by environmental cues, ongoing bulbar neurogenesis could be associated with improved olfactory memory.

Abstract: The peripheral olfactory system is able to recover after injury, i.e., the olfactory epithelium reconstitutes, the olfactory nerve regenerates, and the olfactory bulb is reinnervated, with a facility that is unique within the mammalian nervous system. Cell renewal in the epithelium is directed to replace neurons when they die in normal animals and does so at an accelerated pace after damage to the olfactory nerve. Neurogenesis persists because neuron-competent progenitor cells, including transit amplifying and immediate neuronal precursors, are maintained within the population of globose basal cells. Notwithstanding events in the neuron-depleted epithelium, the death of both non-neuronal cells and neurons directs multipotent globose basal cell progenitors, to give rise individually to sustentacular cells and horizontal basal cells as well as neurons. Multiple growth factors, including TGF-α, FGF2, BMPs, and TGF-βs, are likely to be central in regulating choice points in epitheliopoiesis. Reinnervation of the bulb is rapid and robust. When the nerve is left undisturbed, i.e., by lesioning the epithelium directly, the projection of the reconstituted epithelium onto the bulb is restored to near-normal with respect to rhinotopy and in the targeting of odorant receptor-defined neuronal classes to small clusters of glomeruli in the bulb. However, at its ultimate level, i.e., the convergence of axons expressing the same odorant receptor onto one or a few glomeruli, specificity is not restored unless a substantial number of fibers of the same type are spared. Rather, odorant receptor-defined subclasses of neurons innervate an excessive number of glomeruli in the rough vicinity of their original glomerular targets. Anat Rec (New Anat) 269:33–49, 2002. © 2002 Wiley-Liss, Inc.

Abstract: Objective To investigate the consequences of olfactory loss and explore specific questions related to the effect of duration of olfactory loss, degree of olfactory sensitivity, and cause of the olfactory loss. Patients A total of 278 consecutive patients with hyposmia or anosmia were examined. Results Causes of olfactory loss were categorized as follows: trauma (17%), upper respiratory tract infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%), idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease with increased duration of olfactory loss; and (3) the elderly are more prone to URI olfactory loss than younger patients. Regarding changes in quality of life (QoL), we found that (1) in most patients olfactory loss caused food-related problems; (2) loss in QoL did not change with duration of olfactory loss; (3) younger patients had more complaints than older ones, and women had more complaints than men; (4) complaint scores were higher in hyposmic patients than in anosmic patients; and (5) self-rated depression did not relate to measured olfactory function. Conclusions Among many complaints of olfactory loss, the predominant ones were food related. This loss in QoL seemed to be of greater importance in younger than in older people, and women seem to be affected more strongly than men.

Abstract: The subventricular zone remains mitotically active throughout life in rodents. Studies with tritiated thymidine, which is incorporated into the DNA of mitotic cells, have revealed that the rodent subventricular zone produces neuroblasts that migrate toward the olfactory bulb along the rostral migratory stream. A similar migratory stream has been documented in monkeys by using the thymidine analogue BrdUrd. The same approach showed that neurogenesis occurred in the dentate gyrus of adult primates, including humans. In the present study, experiments combining injections of BrdUrd and the dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindo-carbocyanine, with the immunostaining for molecular markers of neurogenesis (polysialylated neural cell adhesion molecule, β-tubulin-III, collapsin response mediator protein-4, neuronal nuclear protein) in New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have revealed that new neurons are produced in the amygdala, piriform cortex, and adjoining inferior temporal cortex in adult primates. These newborn neurons expressed the antiapoptotic protein Bcl-2 and formed a more-or-less continuous pathway that extended from the tip of the temporal ventricular horn to the deep portion of the temporal lobe. The production of newborn neurons in the amygdala, piriform cortex, and inferior temporal cortex seems to parallel the continuing addition of neurons in the olfactory bulb. These two concomitant phenomena may ensure structural stability and functional plasticity to the primate olfactory system and temporal lobe.

Abstract: Olfactory signal transduction has been well-studied and is generally similar in vertebrates, insects, crustaceans, and nematodes (Ache 1994; Hildebrand and Shepherd 1997; Prasad and Reed 1999). In all of these systems, odorant molecules are detected through interactions with specific G-protein-linked receptors present on the dendrites of olfactory receptor neurons. G-protein activation then produces a second-messenger cascade leading to ion channel activation and receptor neuron depolarization. How is the olfactory system capable of perceiving and discriminating among a myriad of different airborne odorants? One possibility is that these odorants are recognized by a correspondingly large number of receptors. In fact, large numbers of different odorant-receptor genes are found in both mammals (∼1000 genes in mice and rats; Mombaerts 1999) and the roundworm Caenorhabditis elegans (∼800 genes; Bargmann 1998; Robertson 2000). In contrast, recent analyses of the Drosophila melanogaster genome revealed far fewer potential odorant-receptor genes: 60 genes of which only 43 are expressed in the antenna or maxillary palp (Clyne et al. 1999; Gao and Chess 1999; Vosshall et al. 1999, 2000; Vosshall 2001). A related family of 56 receptors is expressed primarily in gustatory neurons (Scott et al. 2001). Why is the variety of odorant-receptor diversity in Drosophila more than an order of magnitude lower than it is in either mammals or C. elegans? Perhaps odorant receptors are not the only molecules involved in odorant recognition by insects. One attractive possibility is that another class of molecules, the odorant-binding proteins (OBPs), contributes substantially to the recognition of odorants in insects. OBPs are small, soluble proteins present at high levels in the fluid surrounding olfactory-receptor neurons (Pelosi 1994). They are generally thought to solubilize hydrophobic odorants and shuttle them to the underlying receptors (Vogt et al. 1991; Pelosi 1994; Prestwich et al. 1995). However, they could potentially function in odorant recognition, perhaps by presentation of the odorant molecule to the underlying receptor (Pelosi 1994; Prestwich et al. 1995). In fact, there is increasing evidence that OBPs do play an active role in odorant recognition rather than merely serving as passive odorant shuttles. One line of evidence is the large number of OBPs present within a variety of insect species. For example, five OBPs have been described in the moth Antheraea pernyi (Breer et al. 1990; Raming et al. 1990; Krieger et al. 1991, 1997). Several studies have shown that the different OBPs found within a single insect species display distinct odorant-binding specificities (Du and Prestwich 1995; Prestwich et al. 1995; Maibeche-Coisne et al. 1997; Plettner et al. 2000). Furthermore, Drosophila that lack the “LUSH” OBP show specific deficits in response to the odorants ethanol or benzaldehyde (Kim et al. 1998; Wang et al. 2001). Also, different OBPs show differential expression patterns in distinct subsets of the olfactory sensory hairs (sensilla) on an insect's antenna (Steinbrecht et al. 1995; Steinbrecht 1996; Park et al. 2000). Each sensillum carries a limited number of olfactory receptor neurons that are exposed only to OBPs present within that particular sensillum. If OBPs and odorant receptors are expressed within different, but overlapping subsets of sensilla, the result would be a mosaic of sensilla with different odorant thresholds. Thus, a moderate number of OBPs could act in a combinatorial manner with a moderate number of odorant receptors to greatly increase the discriminating power of an insect's olfactory system. This combinatorial strategy does not appear to be the case for mammals. Odorant discrimination appears to be largely due to the diversity of olfactory receptors (∼1000; Mombaerts 1999) because only one or a few OBPs are present in the mammalian olfactory mucosa (Tegoni et al. 2000), and they show fairly broad odorant specificities (Lobel et al. 2002). C. elegans also resembles the mammalian system with a large olfactory receptor population (∼800; Bargmann 1998; Robertson 2000). In the case of C. elegans, no OBP has been described (Rubin et al. 2000). Hence, we have two seemingly contrasting situations: Some organisms (mammals and nematodes) have large numbers of olfactory receptors and few or no OBPs, whereas insects have a moderate number of receptors coupled with a moderate number of OBPs. Exactly how many OBPs are there in insects, and how are their genes organized? In this study, we provide a comprehensive examination of OBP-like genes in Drosophila. We find that the Drosophila genome carries 51 potential OBP genes, a number comparable to that of its odorant-receptor genes (Clyne et al. 1999; Gao and Chess 1999; Vosshall et al. 1999, 2000; Vosshall 2001). We find that the majority (73%) of OBP-like genes occur in clusters of four to nine genes; two of these presumptive OBP gene clusters also include an odorant-receptor gene. Our analysis also reveals an apparently monophyletic subfamily of OBP-like proteins whose 12 members have a conserved C terminus.

Abstract: The primary olfactory brain center, the antennal lobe (AL) in insects or the olfactory bulb in vertebrates, is a notable example of a neural network for sensory processing. While physiological prop...

Abstract: We demonstrated recently that transplantation of olfactory ensheathing cells from the nasal olfactory mucosa can promote axonal regeneration after complete transection of the spinal cord in adult rat. Ten weeks after transection and transplantation there was significant recovery of locomotor behaviour and restoration of descending inhibition of spinal cord reflexes, accompanied by growth of axons across the transection site, including serotonergic axons arising from the brainstem raphe nuclei. The present experiment was undertaken to determine whether olfactory ensheathing cells from the olfactory mucosa are capable of promoting regeneration when transplanted into the spinal cord 4 weeks after transection. Under general anaesthesia, thoracic spinal cord at the T10 level was transected completely in adult rats. Four weeks later, the scar tissue and cavities at the transection site were removed to create a 3-4 mm gap. Into this gap, between the cut surfaces of the spinal cord, pieces of olfactory lamina propria were placed. Ten weeks later, the locomotor activity of these animals was significantly improved compared with control animals, which received implants of either pieces of nasal respiratory lamina propria or collagen (Basso, Beattie, Bresnahan Locomotor Rating Scale scores 4.3 + 0.8, n = 6 versus 1.0 + 0.2, n = 10, respectively; P < 0.001). Ten weeks after transplantation the behavioural recovery was still improving. Regrowth of brainstem raphe axons across the transplant site was shown by the presence of serotonergic axons in the spinal cord caudal to the transection site, and by retrograde labelling of cells in the nucleus raphe magnus after injections of fluorogold into the caudal spinal cord. Neither serotonergic axons nor labelled brainstem cells were observed in the control animals. These results indicate that olfactory ensheathing cells from the nasal olfactory lamina propria have the ability to promote spinal cord regeneration when transplanted 4 weeks after complete transection. Olfactory ensheathing cells are accessible and available in the human nose; the present study further supports clinical use of these cells in repairing the human spinal cord via autologous transplantation.

Abstract: Peptidergic Modulation of Identified Function.- Antagonistic Modulation of Neuromuscular Parameters in Crustaceans by the Peptides Proctolin and Allatostatin, Contained in Identified Motor Neurons.- Convergence and Divergence of Cotransmitter Systems in the Crab Stomatogastric Nervous System.- Peptidergic Release Sites Involved in Modulation of the Stomatogastric Nervous System.- Intracellular Signals that Mediate Synaptic Modulation by a FMRFamide-Like Neuropeptide in Crayfish.- Influence of Neuromodulators and Vesicle Docking Related Proteins on Quantal Release.- Hormonal Control.- The Crustacean Neuropeptides of the CHH/MIH/GIH Family: Structures and Biological Activities.- Crustacean Chromatophore: Endocrine Regulation and Intracellular Signalling Systems.- Distributed Circadian Rhythmicity in the Crustacean Nervous System.- Aminergic Modulation of Behavior.- Neural Mechanisms of Dominance Hierarchies in Crayfish.- Aminergic Systems in the Squat Lobster Mundia quadrispina (Anomura, Galatheidae): a Case Made for Comparative Neurobiology.- Amine Effects on Aggression in the Giant Tropical Freshwater Prawn Macrobrachium rosenbergii.- Synaptic Connectivity of Amine-Containing Neurosecretory Cells of Lobsters: Inputs to 5HT- and OCT- Containing Neurons.- Intrinsic Properties of Amine-Containing Neurosecretory Cells of Lobsters: Spontaneous Activity and Autoinhibition.- Quantitative Behavioral Techniques for the Study of Crustacean Aggression.- Aminergic Modulation at the Cellular and Molecular Level.- Multiple Effects of Dopamine on an Identified Motor Neuron Analyzed by Electrophysiological and Optical Imaging Techniques.- A-Current Diversity: Differences in Channel Hardware or Second Messengers?.- Molecular Biology of Crustacea: Unique Opportunities in the Crustacean Nervous System.- Aminergic Modulation of Sensory-Motor Integration in the Walking System of the Crayfish.- Synaptic Mechanisms.- Determinants of Synaptic Strength and Stability at Crustacean Neuromuscular Junctions.- Activity-Dependent Development and Plasticity of Crustacean Motor Terminals.- Crustacean Neuromuscular Glutamatergic and GABAergic Channels with Some Comparison to Drosophila Channels.- Correlation of the Synaptic and Mechanical Properties of Two Slow Fibre Phenotypes in a Crustacean Muscle.- Nitric Oxide and Cyclic GMP Modulate Synaptic Transmission in the Local Circuits of the Crayfish.- Learning and Memory.- Crustaceans as Models to Investigate Memory Illustrated by Extensive Behavioral and Physiological Studies in Chasmagnathus.- Visual Learning in Crabs Investigated by Intracellular Recordings in Vivo.- Olfaction.- A Compound Nose: Functional Organization and Development of Aesthetasc Sensilla.- Molecular Physiology of G-Proteins in Olfactory Transduction and CNS Neurotransmission in the Lobster.- Properties and Functional Role of a Sodium-Activated Nonselective Cation Channel in Lobster Olfactory Receptor Neurons.- Development and Growth Patterns of Olfactory Sensilla in Malacostracan Crustaceans.- Olfactory Centers in the Brain of Freshwater Crayfish.- Development.- Cell Lineage of Crustacean Neuroblasts.- From Stem Cell to Structure: Neurogenesis in the CNS of Decapod Crustaceans.- Adult Neurogenesis in the Central Olfactory Pathway of Decapod Crustaceans.- Role of Modulatory Inputs in the Ontogeny of Neural Networks.- Visual Systems.- The Detection and Analysis of Optic Flow by Crabs: from Eye Movements to Electrophysiology.- Signal Processing in the Crayfish Optic Lobe: Contrast, Motion and Polarization Vision.- Spectral Sensitivity in Crustacean Eyes.- Evolution of Optical Design in the Malacostraca (Crustacea).- Sensory Integration.- Ventilatory Activity in Free-Moving Crayfish Is Indicative of Its Functional State and Perception of External Stimuli.- Sound Production in Crustacea with Special Reference to the Alpheidae.- Sound Perception in Aquatic Crustaceans.- Neural Networks Controlling Vegetative Rhythms.- Connections of the Head to Networks of the Stomatogastric System in Crayfish.- Performance of Neural Networks Controlling Vegetative Rhythms.- Sensory Feedback in the Operating Stomatogastric Nervous System of the Crab (Cancer pagurus).- Circuitry Analysis.- Motor Pattern Switching by an Identified Sensory Neuron in the Lobster Stomatogastric System.- Synaptic Organization of Local Circuit Neurons in the Terminal Abdominal Ganglion of the Crayfish.- Proprioception in the Tailfan of the Crayfish.- Active Shaping of Proprioceptive Message in Crayfish.

Abstract: The nasal epithelium is richly invested with peptidergic (substance P and calcitonin gene-related peptide [CGRP]) trigeminal polymodal nociceptors, which respond to numerous odorants as well as irritants. Peptidergic trigeminal sensory fibers also enter the glomerular layer of the olfactory bulb. To test whether the trigeminal fibers in the olfactory bulb are collaterals of the epithelial trigeminal fibers, we utilized dual retrograde labeling techniques in rats to identify the trigeminal ganglion cells innervating each of these territories. Nuclear Yellow was injected into the dorsal nasal epithelium, and True Blue was injected into the olfactory bulb of the same side. Following a survival period of 3-7 days, the trigeminal ganglion contained double-labeled, small (11.8 x 8.0 microm), ellipsoid ganglion cells within the ethmoid nerve region of the ganglion. Tracer injections into the spinal trigeminal complex established that these branched trigeminal ganglion cells also extended an axon into the brainstem. These results indicate that some trigeminal ganglion cells with sensory endings in the nasal epithelium also have branches reaching directly into both the olfactory bulb and the spinal trigeminal complex. These trigeminal ganglion cells are unique among primary sensory neurons in having two branches entering the central nervous system at widely distant points. Furthermore, the collateral innervation of the epithelium and bulb may provide an avenue whereby nasal irritants could affect processing of coincident olfactory stimuli.

Abstract: ▪ Abstract The olfactory system sits at the interface of the environment and the nervous system and is responsible for correctly coding sensory information from thousands of odorous stimuli. Many theories existed regarding the signal transduction mechanism that mediates this difficult task. The discovery that odorant transduction utilizes a unique variation (a novel family of G protein–coupled receptors) based upon a very common theme (the G protein–coupled adenylyl cyclase cascade) to accomplish its vital task emphasized the power and versatility of this motif. We now must understand the downstream consequences of this cascade that regulates multiple second messengers and perhaps even gene transcription in response to the initial interaction of ligand with G protein–coupled receptor.

Abstract: Objectives: The review outlines characteristics of the intranasal trigeminal chemosensory system. In addition, it provides selective comparisons of the trigeminal and olfactory systems, the two of which interact at multiple levels. Results and Conclusions: This interaction between the trigeminal and olfactory systems is an important determinant of sensations of odor. Further, it appears to change as a result of aging and disease. Thus, the interaction between the olfactory and trigeminal systems is not straightforward and may be difficult to predict, but it has a powerful influence on the perception of odors.

Abstract: The mammalian olfactory system consists of two anatomically segregated structures, the main olfactory system and the vomeronasal system, which each detect distinct types of chemical stimuli in the environment. During development, sensory neurons establish precise axonal connections with their respective targets within the olfactory bulb. The specificity of the odorant or vomeronasal receptor expressed by the sensory neuron is crucial in this process, yet it is less clear which of the more conventional axon guidance molecules are involved. Here, we show that neuropilin-2, a coreceptor for some of the class 3 semaphorins, is expressed in subpopulations of olfactory and vomeronasal sensory neurons. We generated a knock-out mutation in the neuropilin-2 gene by gene targeting in embryonic stem cells. Neuropilin-2 mutant mice exhibit profound and distinct effects on target innervation within the olfactory bulb. In the main olfactory system, axons of olfactory sensory neurons penetrate into the deeper layers of the main olfactory bulb. In the vomeronasal system, axonal fasciculation within the vomeronasal nerve is affected; some axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb.

Abstract: Experiments examining the dosimetry of inhaled manganese generally focus on pulmonary deposition and subsequent delivery of manganese in arterial blood to the brain. Growing evidence suggests that nasal deposition and transport along olfactory neurons represents another route by which inhaled manganese is delivered to certain regions of the rat brain. The purpose of this study was to evaluate the olfactory uptake and direct brain delivery of inhaled manganese phosphate ((54)MnHPO(4)). Male, 8-wk-old, CD rats with either both nostrils patent or the right nostril occluded underwent a single, 90-min, nose-only exposure to a (54)MnHPO(4) aerosol (0.39 mg (54)Mn/m(3); MMAD 1.68 microm, sigma(g) 1.42). The left and right sides of the nose, olfactory pathway, striatum, cerebellum, and rest of the brain were evaluated immediately after the end of the (54)MnHPO(4) exposure and at 1, 2, 4, 8, and 21 d postexposure with gamma spectrometry and autoradiography. Rats with two patent nostrils had equivalent (54)Mn concentrations on both sides of the nose, olfactory bulb, and striatum, while asymmetrical (54)Mn delivery occurred in rats with one occluded nostril. High levels of (54)Mn activity were observed in the olfactory bulb and tubercle on the same side (i.e., ipsilateral) to the open nostril within 1-2 d following (54)MnHPO(4) exposure, while brain and nose samples on the side ipsilateral to the nostril occlusion had negligible levels of (54)Mn activity. Our results demonstrate that the olfactory route contributes to (54)Mn delivery to the rat olfactory bulb and tubercle. However, this pathway does not significantly contribute to striatal (54)Mn concentrations following a single, short-term inhalation exposure to (54)MnHPO(4).

Abstract: Objectives To develop a test kit for the simple assessment of retronasal olfactory function and to compare orthonasal and retronasal olfactory function in healthy subjects and patients with olfactory disorders. Design and Patients We tested 230 individuals with normosmia, hyposmia, and anosmia using grocery-available powders. Initially, 30 different substances were investigated. Subjects identified each substance using a list with 4 verbal items (forced choice). After preliminary experiments, 20 items were selected according to the degree to which they were identified by normosmic and anosmic subjects. Orthonasal olfactory function was assessed psychophysically using "sniffin' sticks," which includes tests for odor identification, discrimination, and butanol odor thresholds. In addition, anosmia was confirmed electrophysiologically by means of olfactory-evoked potentials. Results In healthy subjects, there was a test-retest reliability correlation of r 27 = 0.76 for retronasal olfactory function, which is similar to other odor identification tests. Retronasal testing in normosmic subjects allowed for the discrimination of sex-related differences, with women scoring higher than men ( P = .007), and the identification of a slight decrease with age ( r 120 = −0.20; P = .03). Orthonasal and retronasal identification of odors was found to correlate ( r 86 = 0.78; P P P = .03). No difference was found between patients with anosmia of different origin. Conclusion Results of the present investigation indicate that the assessment of retronasal olfactory function is possible using oral stimulus presentation.

Abstract: The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium1. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections2. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 → M71, in which a functionally characterized receptor, rI73,4, has been substituted into the M71 receptor locus5. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 → M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 → M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb.

Abstract: * Retina (continuation) * Optic nerves, chiasma and optic radiations * Lateral geniculate body and pulvinar * Thalamus (continuatiuon) * Thalamus (continuation) * Nuclei of the subthalamic and hypothalamic regions * Thalamus (continuatiuon) * Corpus striatum * General structural plan of the cerebral cortex * Regional cerebral cortex * Auditory cortex * Motor or sensory-motor cortex * Olfactory apparatus * Second-order and third-order olfactory centers * Pathways originated in the temporal olfactory cortex * Fourth-order olfactory centers: the hippocampal and dentate gyri * Efferent pathways and subordinate nuclei of the hippocampal gyrus * Cingulate gyrus - Cingulum * Comparative structure of the celebral cortex * Histogenesis of the cerebral cortex * Anatomo-physiologic considerations about the cerebrum * Autonomic ganglia * Appendix I: Table of equivalent figure numbers * Appendix II: Taxonomy glossary

Abstract: Olfactory loss is a prominent symptom in idiopathic Parkinson's disease (IPD). Experiment 1 re-investigated the diagnostic value of psychophysical testing in the differentiation between idiopathic Parkinson disease (IPD) from non-IPD; 50 consecutive PS patients participated. In Experiment 2 five de-novo patients received 3 olfactory tests spread over a period of appoximately one year. Nineteen IPD patients were anosmic, and 18 were hyposmic. All but one patient with MSA and PSP had mild/moderate hyposmia. Normosmia was found in CBD/misdiagnosed PS/psychogenic movement disorder. In Experiment 2, one of the de-novo patients was normosmic, 3 hyposmic, and 1 anosmic. Follow up investigations indicated decreased olfactory function in 3 patients while it improved in one. The normosmic patient retained olfactory abilities. This patient failed to respond to pharmacological treatment. In summary, olfactory tests differentiate IPD from non-IPD. Furthermore, tests of olfactory function may also be of interest in investigations related to treatment of PS.

Abstract: Perceptual learning has been demonstrated in several thalamocortical sensory systems wherein experience enhances sensory acuity for trained stimuli. This perceptual learning is believed to be dependent on changes in sensory cortical receptive fields. Sensory experience and learning also modifies receptive fields and neural response patterns in the mammalian olfactory system; however, to date there has been little reported evidence of learned changes in behavioral olfactory acuity. The present report used a bradycardial orienting response and cross-habituation paradigm that allowed assessment of behavioral discrimination of nearly novel odorants, and then used the same paradigm to examine odorant discrimination after associative olfactory conditioning with similar or dissimilar odorants. The results demonstrate that associative conditioning can enhance olfactory acuity for odors that are the same as or similar to the learned odorant, but not for odors dissimilar to the learned odorant. Furthermore, scopolamine injected before associative conditioning can block the acquisition of this learned enhancement in olfactory acuity. These results could have important implications for mechanisms of olfactory perception and memory, as well as for correlating behavioral olfactory acuity with observed spatial representations of odorant features in the olfactory system.

Abstract: Objectives/hypothesis The study aimed to investigate the potential therapeutic effects of alpha-lipoic acid in olfactory loss following infections of the upper respiratory tract. Possible mechanisms of actions include the release of nerve growth factor and antioxidative effects, both of which may be helpful in the regeneration of olfactory receptor neurons. Study design Unblinded, prospective clinical trial. Methods A total of 23 patients participated (13 women, 10 men; mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range, 4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic acid was used orally at a dose of 600 mg/day; it was prescribed for an average period of 4.5 months. Olfactory function was assessed using olfactory tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. Results Seven patients (30%) showed no change in olfactory function. Two patients (9%) exhibited a moderate decrease in olfactory function; in contrast, six patients (26%) showed moderate and eight patients (35%) remarkable increase in olfactory function. Two of the 4 patients with functional anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall, this resulted in a significant improvement in olfactory function following treatment (P =.002). At the end of treatment parosmias were less frequent (22%) than at the beginning of therapy (48%). Interestingly, recovery of olfactory function appeared to be more pronounced in younger patients than in patients above the age of 60 years (P =.018). Conclusions The results indicate that alpha-lipoic acid may be helpful in patients with olfactory loss after upper respiratory tract infection. However, to judge the true potential of this treatment, the outcome of double-blind, placebo-controlled studies in large groups of patients must be awaited, especially when considering the relatively high rate of spontaneous recovery in olfactory loss after upper respiratory tract infection.

Abstract: Follow-up T(1)-weighted 3D gradient-echo MRI (2.35 T) of murine brain in vivo (N = 5) at 120 microm isotropic resolution revealed spatially distinct signal increases 6-48 hr after subcutaneous application of MnCl(2) (20 mg/kg). The effects result from a shortening of the water proton T(1) relaxation time due to the presence of unchelated paramagnetic Mn(2+) ions, which access the brain by systemic circulation and crossing of the blood-brain barrier (BBB). A pronounced Mn(2+)-induced signal enhancement was first seen in structures without a BBB, such as the choroid plexus, pituitary gland, and pineal gland. Within 24 hr after administration, Mn(2+) contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and the CA3 subfield of the hippocampus. The affinity of Mn(2+) to various brain systems suggests the neuronal uptake of Mn(2+) ions from the extracellular space and subsequent axonal transport. Thus, at least part of the Mn(2+) contrast reflects a functional brain response of behaving animals, for example, in the olfactory system. In vivo MRI staining of the brain by systemic administration of MnCl(2) may contribute to phenotyping mutant mice with morphologic and functional alterations of the central nervous system.

Abstract: The olfactory system detects small differences in the composition of natural odorants, made up of hundreds of molecules. Odorous quality is hypothetically represented by a combinatorial code: activation of distinct but overlapping subsets of olfactory receptors resulting in activation of a distinct subset of glomeruli in the main olfactory bulb (MOB). Here we show that modification of a single gene (the K gene of the major histocompatibility locus), which results in a subtle change in the odiferous quality of urine, causes a small but significant change in the composition of urine volatiles and consequently the evoked glomerular activation pattern in the MOB. The magnitude of disparity between urine-evoked glomerular activation patterns is predictive of the extent of (1) the genetic difference among the urine donors, (2) the difference in the chemical composition of urine, and (3) the odor detector's ability to discriminate. These data on natural odors are consistent with the combinatorial code hypothesis and identify subsets of glomeruli that are apt to play a significant role in mediating individual recognition.

Abstract: A new recombinant vesicular stomatitis virus (rVSV) that expresses green fluorescent protein (GFP) on the cytoplasmic domain of the VSV glycoprotein (G protein) was used in the mouse as a model for studying brain infections by a member of the Mononegavirales order that can cause permanent changes in behavior. After nasal administration, virus moved down the olfactory nerve, first to periglomerular cells, then past the mitral cell layer to granule cells, and finally to the subventricular zone. Eight days postinoculation, rVSV was eliminated from the olfactory bulb. Little sign of infection could be found outside the olfactory system, suggesting that anterograde or retrograde axonal transport of rVSV was an unlikely mechanism for movement of rVSV out of the bulb. When administered intracerebrally by microinjection, rVSV spread rapidly within the brain, with strong infection at the site of injection and at some specific periventricular regions of the brain, including the dorsal raphe, locus coeruleus, and midline thalamus; the ventricular system may play a key role in rapid rVSV dispersion within the brain. Thus, the lack of VSV movement out of the olfactory system was not due to the absence of potential for infections in other brain regions. In cultures of both mouse and human central nervous system (CNS) cells, rVSV inoculations resulted in productive infection, expression of the G-GFP fusion protein in the dendritic and somatic plasma membrane, and death of all neurons and glia, as detected by ethidium homodimer nuclear staining. Although considered a neurotropic virus, rVSV also infected heart, skin, and kidney cells in dispersed cultures. rVSV showed a preference for immature neurons in vitro, as shown by enhanced viral infection in developing hippocampal cultures and in the outer granule cell layer in slices of developing cerebellum. Together, these data suggest a relative affinity of rVSV for some neuronal types in the CNS, adding to our understanding of the long-lasting changes in rodent behavior found after transient VSV infection.

Abstract: The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active ...

Abstract: Whether different odorous compounds (odorants) are processed by different cerebral circuits is presently unknown. A first step to address this complicated issue is to investigate how the cerebral regions mediating signals from olfactory (i.e., unimodal) odorants, differ from those mediating the olfactory + trigeminal (i.e., bimodal) odorants. [15O]-H2O-PET scans were conducted in 12 healthy females during three separate conditions: birhinal, passive smelling of: 1) the unimodal odorant vanillin; 2) the bimodal odorant acetone; and 3) odorless air. Significant activations were calculated contrasting vanillin to air, acetone to air, and deactivations, running these contrasts in the opposite direction. Smelling of vanillin activated bilaterally the amygdala and piriform cortex. These regions were only engaged slightly by acetone. Instead, strong activations were found in the anterior and central insula and claustrum, the posterior portion of anterior cingulate, the somatosensory cortex (SI for face), cerebellum, ventral medial (VMPo) and dorsal medial (MDvc) thalamus, the lateral hypothalamus, and pons/medulla. In parallel, the somatosensory (SI, below central representation of face), secondary visual and auditory cortices, as well as the supplementary motor area and the parahippocampal gyri were deactivated. No deactivations were observed with vanillin, although the odor components of acetone and vanillin were rated similarly intense (75 +/- 17 mm vs. 61 +/- 22 mm, NS). The differentiated pattern of cerebral activation during odorant perception seems to be dependent on the signal transducing cranial nerves involved. In contrast to vanillin, which solely activates the olfactory cortex, acetone engages predominantly trigeminal projections from the nasal mucosa. Acetone's limited activation of the olfactory cortex may result from a cross-modal interaction, with inhibition of acetone's odor component by its trigeminal component.

Abstract: Gene knockout technologies have been used to elevate the mouse as a model species. However, little work has examined age and strain differences in the mouse olfactory system. The present study compared the olfactory bulbs of mature (6 month) and aged (24 month) males of BALB/cBy, C57BL/6J, and DBA/2 strains. Volumes of the glomerular (GLM), external plexiform (EPL), and mitral/granule cell (MIG) layers varied little from strain to strain. Volume measurements increased with age even when corrected for body weight differences. Two nonoverlapping interneuron populations were examined with immunohistochemistry. Staining for the calcium binding protein calretinin varied little between strains, but age-related increases in staining were seen in EPL of C57BL/6J mice. Typical patterns of tyrosine hydroxylase immunoreactivity were observed in all subjects except for old DBA/2 mice, which evidenced considerable staining in submitral areas. Age-related increases were observed in BALB/cBy and DBA/2 mice but not in the C57BL/6J strain. Glial fibrillary acidic protein staining was similar in old BALB/cBy and DBA/2 mice, with astrocytes in all layers of the bulb, but more concentrated in the MIG. However, C57BL/6J tissue revealed very large astrocytes relatively evenly distributed in all layers. Cell proliferation dropped dramatically with age. Labeled cells could still be observed along the lateral ventricles, but very few were observed within the rostral migratory stream or subventricular zone. Although TUNEL labeling revealed many apoptotic figures in the granule cell layer of young subjects, almost no staining was seen in aged mice.