Abstract: The upper cervical corticospinal tract was transected on one side in adult rats. A suspension of ensheathing cells cultured from adult rat olfactory bulb was injected into the lesion site. This induced unbranched, elongative growth of the cut corticospinal axons. The axons grew through the transplant and continued to regenerate into the denervated caudal host tract. Rats with complete transections and no transplanted cells did not use the forepaw on the lesioned side for directed reaching. Rats in which the transplanted cells had formed a continuous bridge across the lesion exhibited directed forepaw reaching on the lesioned side.

Abstract: Most animals depend on the identification of odours to locate food or to find mating partners. To accomplish this, the olfactory system must recognize relative concentrations of a large number of substances by analysing complex patterns of chemoreceptor activations1,2, but how these patterns are represented in the brain is not well understood. Previous studies indicated that odours evoke specific patterns of activity in olfactory sensory centres3–7 and led to the hypothesis that single glomeruli in the olfactory bulb of mammals respond to particular receptor types8–10. We made optical recordings in vivo in the honeybee brain to investigate neuronal population responses to odorants delivered naturally to the animal. We report here that odours evoked specific spatio–temporal excitation patterns in the antennal lobe, the structural and functional analogue of the olfactory bulb11. Specific ensembles of active glomeruli represent odours in a combinatorial manner. A comparison between different individuals shows remarkable similarities for a pheromone component, but not for general flower odours. Mixtures evoked patterns that were combinations of the single odorant responses. These combinations were not fully additive, however, indicating inhibitory effects on single glomeruli. Such interactions could be crucial for the formation of singular codes for complex odour blends.

Abstract: OBJECTIVE: To evaluate olfactory function in Parkinson's disease. METHODS: A standardised odour identification test was used, together with an evoked potential assessment with hydrogen sulphide. In addition, histological analysis was performed on the olfactory bulbs of cadavers who died from Parkinson's disease. RESULTS: Over 70% of patients studied (71 of 96) were outside the 95% limit of normal on the identification test in an age matched sample and there was an unusual pattern of selective loss to certain odours, not hitherto described. The evoked potentials were significantly delayed but of comparable amplitude to a control matched population. Of the 73 patients studied only 37 had a technically satisfactory record containing a clear response to both gases and of these, 12 were delayed. For H2S there was more delay on stimulating the right nostril than the left. Some patients with normal smell identification test scores had delayed evoked potentials. In the pathological examination of olfactory bulbs from eight brains, changes characteristic of Parkinson's disease (Lewy bodies) were seen in every olfactory bulb, particularly in the anterior olfactory nucleus, and were sufficiently distinct to allow a presumptive diagnosis of Parkinson's disease. CONCLUSIONS: Olfactory damage in Parkinson's disease is consistent and severe and may provide an important clue to the aetiology of the disease.

Abstract: Hydroxyurea (HU) treatment of early first instar larvae in Drosophila was previously shown to ablate a single dividing lateral neuroblast (LNb) in the brain. Early larval HU application to P[GAL4] strains that label specific neuron types enabled us to identify the origins of the two major classes of interneurons in the olfactory system. HU treatment resulted in the loss of antennal lobe local interneurons and of a subset of relay interneurons (RI), elements usually projecting to the calyx and the lateral protocerebrum (LPR). Other RI were resistant to HU and still projected to the LPR. However, they formed no collaterals in the calyx region (which was also ablated), suggesting that their survival does not depend on targets in the calyx. Hence, the ablated interneurons were derived from the LNb, whereas the HU-resistant elements originated from neuroblasts which begin to divide later in larval life. Developmental GAL4 expression patterns suggested that differentiated RI are present at the larval stage already and may be retained through metamorphosis.

Abstract: Background: The ability to smell is commonly altered by head trauma (HT). However, the nature, prevalence, prognosis, and etiology of such alterations are poorly understood. Objectives: To quantitatively determine the degree of olfactory function in patients with HT-related chemosensory complaints and to examine the influences of age, sex, HT severity, time since HT, and other variables on such function. Also, to use quantitative magnetic resonance imaging (MRI) to establish whether and to what degree damage to the olfactory bulbs and tracts, frontal lobes, and temporal lobes occurs. Patients and Methods: Two hundred sixty-eight patients with HT from the University of Pennsylvania Smell and Taste Center, Philadelphia, were administered a quantitative odor identification test, a depression inventory, and a medical history questionnaire; 66 were retested after individual test-retest periods ranging from 1 month to 13 years. The volume of olfactory-related brain structures was determined in 15 patients and 15 controls using MRI. Results: One hundred seventy-nine patients (66.8%) had anosmia, 55 (20.5%) had microsmia, and 34 (12.7%) had normosmia. Frontal impacts produced less dysfunction than back or side impacts. Of the 66 retested patients, 24 (36%) improved slightly, 30 (45%) had no change, and 12 (18%) worsened; only 3 patients, none of whom initially had anosmia, regained normal olfactory function. Trauma severity was related to olfactory test scores in patients with microsmia. Parosmia prevalence decreased from 41.1% to 15.4% over an 8-year posttrauma period. Olfactory bulb and tract volumes of male, but not female, patients with HT were greatly reduced relative to volumes of controls. Conclusions: Patients complaining of HT-related olfactory dysfunction typically have anosmia and rarely regain normal olfactory ability, parosmia prevalence decreases over time in such patients, and damage to olfaction-related brain structures can be observed in most such patients using an appropriate MRI protocol.

Abstract: Sheep learn to recognize the odours of their lambs within two hours of giving birth, and this learning involves synaptic changes within the olfactory bulb Specifically, mitral cells become increasingly responsive to the learned odour, which stimulates release of both glutamate and GABA (gamma-aminobutyric acid) neurotransmitters from the reciprocal synapses between the excitatory mitral cells and inhibitory granule cells Nitric oxide (NO) has been implicated in synaptic plasticity in other regions of the brain as a result of its modulation of cyclic GMP levels Here we investigate the possible role of NO in olfactory learning We find that the neuronal enzyme nitric oxide synthase (nNOS) is expressed in both mitral and granule cells, whereas the guanylyl cyclase subunits that are required for NO stimulation of cGMP formation are expressed only in mitral cells Immediately after birth, glutamate levels rise, inducing formation of NO and cGMP, which potentiate glutamate release at the mitral-to-granule cell synapses Inhibition of nNOS or guanylyl cyclase activity prevents both the potentiation of glutamate release and formation of the olfactory memory The effects of nNOS inhibition can be reversed by infusion of NO into the olfactory bulb Once memory has formed, however, inhibition of nNOS or guanylyl cyclase activity cannot impair either its recall or the neurochemical release evoked by the learned lamb odour Nitric oxide therefore seems to act as a retrograde and/or intracellular messenger, being released from both mitral and granule cells to potentiate glutamate release from mitral cells by modulating cGMP concentrations We propose that the resulting changes in the functional circuitry of the olfactory bulb underlie the formation of olfactory memories

Abstract: Pax-6 in vertebrates and its homolog eyeless in Drosophila are known to be essential for eye development. Here we investigate the role of Pax-6 in eye development in another major systematic group, molluscs. We demonstrate that alternatively spliced RNAs derived from a single Pax-6 gene in the squid (Loligo opalescens) are expressed in the embryonic eye, olfactory organ, brain, and arms. Despite significant sequence differences between squid Pax-6 and Drosophila eyeless in the region outside the paired- and homeodomains, squid Pax-6 is able to induce the formation of ectopic eyes in Drosophila. Our results support the idea that Pax-6 related genes are necessary for eye and olfactory system formation throughout the animal kingdom.

Abstract: Part 1 Overview: the many themes of neural organization - structure, function, dynamics a structural overview - an embryological perspective on neural structure and motility, the modular architectonics principle, multiple models of modularity a functional overview - schema theory and functional neuroscience, schemas for "rana computatrix", schemas for Saccades, schemas for reaching and grasping, representing space and time a dynamical overview - neurodynamical system theory, oscillatory behaviour in neural systems, chaotic behaviour in neural systems - some facts and models, self-organization and the development of the nervous system, learning rules. Part 2 Interacting systems of the brain: the olfactory system - anatomical system, electrical patterns in the olfactory bulb and olfactory cortex, development, learning and memory in the olfactory system hippocampus - anatomical organization, electrical activity patterns, brain states and long-term potentiation, hippocampal function and cognitive maps, hippocampal function and human memory thalamus - nuclei of the thalamus, thalamus and sensory systems, thalamocortical loops and cooperative computation cerebral cortex -structural overview, primary visual cortex - the paradigm of modular architectonics, thalamocortical oscillators, frontoparietal interactions, learning of coordinated behaviours, from action-oriented perception to cognition cerebellum - phylogeny and ontogeny of the cerebellum, structural organization of the cerebellar cortex and nuclei, the cerebellum as a learning machine, cerebellar adaptation of movement generation, the cerebellum and mental activity basal ganglia -structure of the basal ganglia, diseases of the basal ganglia, self-reorganization of the striatum, role of basal ganglia in saccade control, roles of the basal ganglia in motor coordination and learning prospects for a neuroscience of cognition - following the threads - the book in perspective, multiple levels, multiple methodologies and the need for their integration, implications and outlook for cognitive neuroscience. Part 3 Appendices: A - neural simulation language B -brain models on the Web.

Abstract: The general features of the olfactory system are remarkably consistent across vertebrates. A phylogenetic analysis of central olfactory projections indicates that at least three distinct olfactory subsystems may be broadly present in vertebrates and that a fourth, the accessory olfactory or vomeronasal system, arose in tetrapods. The origin and function of the vomeronasal system have been the subject of much controversy, but some conclusions can be drawn. The vomeronasal system did not arise as an adaptation to terrestrial life, as indicated by the presence of a vomeronasal system in modern aquatic amphibians and the increasing paleontological evidence that the last common ancestor of amphibians and amniotes was aquatic. The vomeronasal system is involved in both foraging and reproductive behaviors in reptiles and has been shown to be involved in some pheromonally mediated behaviors in mammals. However, among mammals, some pheromonal responses are not mediated by the vomeronasal system, and the possible involvement of the vomeronasal system in other type of behaviors has not yet been investigated. Thus, the relative functions of the olfactory and vomeronasal systems of tetrapods remain unclear. Other hypotheses that features of the olfactory system are specialized for aquatic chemoreception or for pheromone detection are similarly insupportable. For example, the suggestion that members of the olfactory receptor family can be separated into two groups that function for transduction of air-borne or water-borne odorants is contradicted by the presence of both groups in aquatic amphibians and by a phylogenetic analysis of the sequences for these genes. Interestingly, the putative odorant receptors from the vomeronasal epithelium share little sequence similarity with those from the olfactory epithelium, indicating that these receptors may have been independently co-opted from the larger family of seven transmembrane domain receptors for use in odor transduction. A phylogenetic analysis of the distribution of olfactory receptor cell types indicates that microvillar olfactory receptor cells are widespread among vertebrates and are not restricted to aquatic animals or to the vomeronasal epithelium of tetrapods. Previous suggestions that all microvillar receptor cells are specialized for the detection of pheromones are not tenable. Attempts to recognize features of the olfactory system that are common to all vertebrates and might be specialized for the detection of pheromones vs. more general odorants, or for the detection of water-borne vs. air-borne odorants, are not supported by current evidence.

Abstract: PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cin...

Abstract: Collapsin-1 is a member of the semaphorin family of signaling molecules that acts as a repellent for growing spinal sensory axons. We have constructed a chimeric collapsin-1/alkaline phosphatase probe to visualize putative collapsin-1 receptors in vitro and in situ. As predicted by the activity profile of collapsin-1, the probe binds spinal sensory tracts, ventral spinal roots, and the sympathetic chain but does not bind retinal axons. In addition, we find that the probe binds sensory axons arising from the olfactory epithelium and some, but not all, cranial sensory nerves. As predicted by these binding studies, in vitro assays demonstrate that primary olfactory sensory, trigeminal, and jugular ganglion growth cones collapse in the presence of soluble collapsin-1. Comparing the expression pattern of collapsin-1 with the trajectories of collapsin-1 responsive axons suggests that in both the spinal cord and the olfactory bulb, collapsin-1 prevents premature entry of sensory axons into their target and helps determine the final location of sensory terminations.

Abstract: Decrease of olfactory function in patients with Parkinson's disease (PD) has been reported by several authors. The current study investigated olfaction in PD patients using olfactory event-related potentials (OERPs) as an electrophysiologic correlate of olfactory function in combination with psychophysical testing. A specific focus was the influence of antiparkinsonian drugs. We investigated PD patients treated with antiparkinsonian drugs (n = 13) and PD patients who received no pharmacologic treatment (n = 18). They were compared to age- and sex-matched control subjects (n = 38). To obtain OERPs, stimulants were chosen to stimulate specifically the olfactory nerve (2.1 ppm vanillin, 0.8 ppm H2S). In addition, chemosomatosensory event-related potentials were recorded after trigeminal stimulation with 52% v/v CO2. Moreover, the subjects' ability to identify and to discriminate odorants was tested by means of a "squeeze bottle" technique. The study yielded the following major results: (1) Odor identification was impaired in PD patients. It was not influenced by treatment with antiparkinsonian drugs. (2) The OERP latencies were prolonged in both PD patients taking and not taking antiparkinsonian drugs; however, this effect was more pronounced in PD patients taking antiparkinsonian drugs. (3) The intranasal chemosensory trigeminal system seemingly was neither affected by the neuronal degeneration seen in PD nor by treatment with antiparkinsonian drugs.

Abstract: Background: Smell impairment affects 1% to 2% of Americans and leads to frequent physician visits. Olfactory testing is available in chemosensory centers, but not as part of a routine cranial nerve examination. The alcohol sniff test (AST), which uses the standard 70% isopropyl alcohol pad, was developed as a quick, reliable measure of olfactory function. Methods: Sixty-four patients and 36 healthy control subjects (N=100) were tested with the AST and with a standard butanol threshold test. Results: The AST reliably, consistently, and correctly measured olfactory function. Conclusion: The AST is a rapid, reliable olfactory test that can be used for screening olfactory function and should be incorporated in the routine cranial nerve examination. Arch Otolaryngol Head Neck Surg. 1997;123:591-594

Abstract: Over the last fifteen years, we have witnessed a rapid expansion in the development of artificial odour sensing systems, or so called 'electronic nose' systems. Whilst the power of this approach to flavour analysis has undoubtedly been demonstrated by its recent application to various complex odours, it will be argued that the original research programme, aimed at developing a comparative model of the biological olfactory pathway, has degenerated into an attempt to obtain an ad hoc workable system, based around readily available sensor and pattern recognition (PARC) technologies. At the time, the first 'model' nose system reflected the limited understanding of sensory information processing carried out within the biological olfactory pathway. We are now presented with an opportunity to evaluate and re-assess the architecture for an electronic nose, in view of the recent advances in understanding the key processing principals exploited by the olfactory bulb and cortex in the identification and characterisation of molecular stimuli. In Part I of this paper, the rapid developments in the understanding of the information processing performed by the biological olfactory system are critically reviewed, and its relevance to current research in artificial olfaction is considered. Not only have the initial biochemical pathways involved in the transduction of odour stimuli been uncovered, but also computational models of the key synaptic circuits have advanced to the point where network simulations are clearly capable of odour discrimination. The key processing principles exploited in the olfactory pathway for overcoming operating constraints such as sensor drift/degeneration, limited sensitivity, and xenobiotic response are highlighted, so that their integration into the electronic analogue may be explored in Part II.

Abstract: We have evaluated the role of retinoid signaling in the early development of the olfactory epithelium and olfactory bulb. When retinoid-mediated gene expression is blocked briefly in mouse embryos at midgestation with citral (a general alcohol dehydrogenase antagonist that is thought to interfere with retinoid synthesis), the spectrum of morphogenetic abnormalities includes disruption of olfactory pathway development. It is difficult, however, to assess the specificity of this pharmacological manipulation, insofar as it also compromises several other aspects of central nervous system development. In homozygous Pax6 mutant mice (small eye: Pax6Sey-Neu), there is a more discrete lesion to the olfactory pathway: The epithelium and bulb cannot be recognized at any time during development, whereas other forebrain subdivisions can still be recognized. This loss of the entire primary olfactory pathway is accompanied by a failure of retinoid-mediated gene expression limited to the frontonasal region and forebrain. Retinoid receptors are expressed in the forebrain of Pax6Sey-Neu/Pax6Sey-Neu embryos, and the mutant forebrain remains responsive to exogenous retinoic acid. However, in Pax6Sey-Neu/Pax6Sey-Neu embryos, retinoic acid (RA) is not produced by the frontonasal mesenchyme, which normally provides local retinoid signals to the placode and forebrain. Together, these results suggest that local retinoid signaling is essential for the normal development of the mammalian olfactory pathway. J. Comp. Neurol. 379:171–184, 1997. © 1997 Wiley-Liss, Inc.

Abstract: Objective: To establish the efficacy of topical corticosteroid nasal spray treatment of severe olfactory loss associated with severe nasal and sinus disease. Design: Efficacy before and after open-label trial of topical corticosteroid nasal spray used exclusively in the headdown-forward position. Setting: Taste and smell clinic of a university teaching hospital and research facility. Patients: Taste and smell clinic patients with anosmia or severe hyposmia associated with paranasal sinus disease and nasal polyposis including 39 of 45 patients recruited from 1988 to 1994 who completed the topical corticosteroid treatment course and returned for subsequent testing. Intervention: At least 8 weeks of treatment with flunisolide (Nasalide), 2 sprays in each nostril twice a day, with concurrent antibiotic treatment of any bacterial infection. Main Outcome Measures: Subjective olfactory symptoms, objective olfactory function tests, and otolaryngological evaluation (including endoscopic examination). Results: Olfactory scores significantly improved following treatment ( P P Conclusion: Topical corticosteroid nasal spray administered in a head-down-forward position is an effective treatment of severe olfactory loss associated with severe nasal and sinus disease. Arch Otolaryngol Head Neck Surg. 1997;123:367-372

Abstract: 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.

Abstract: Chemosensory event-related potentials (CSERP) can be used to examine central nervous odor processing. An important question for understanding odor perception is how different concentrations are processed. In the present study two odors were chosen which activate either the olfactory (linalool) or the trigeminal (menthol) system. Both odors were presented to 11 subjects in four different concentrations. Four subjects had to attend actively to the odors while the others perceived the odors under passive attention. The results showed that increased concentrations of the olfactory stimulus resulted in shorter latencies of the N1 component but did not affect the amplitudes of the CSERP. However, the amplitudes of the stimulus dependent, exogenous components (N1, P2) increased with higher concentrations of the trigeminal stimulus. The amplitude of the late positive complex, which reflects endogenous processes, was usually larger when the odorous stimuli had to be attended to actively. It is concluded that olfactory intensity coding results in a qualitatively different but not in a stronger neuronal response of the human brain.

Abstract: Christensen, Thomas A. and John G. Hildebrand. Coincident stimulation with pheromone components improves temporal pattern resolution in central olfactory neurons. J. Neurophysiol. 77: 775–781, 1997...