Michael Leon

• PhD
• University of California, Irvine

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions...

Objective Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults. Methods Male and female older adults (N = 43), age 60–85, we...

The loss of olfactory stimulation correlates well with at least 68 widely differing neurological disorders, including depression, and we raise the possibility that this relationship may be causal. That is, it seems possible that olfactory loss makes the brain vulnerable to expressing the symptoms of these neurological disorders, while daily olfacto...

The human brain sustains a slow but progressive decline in function as it ages and these changes are particularly profound in cognitive processing. A potential contributor to this deterioration is the gradual decline in the functioning of multiple sensory systems and the effects they have on areas of the brain that mediate cognitive function. In ol...

We examine the science and evidence supporting cognitive behavior therapy (CBT) for the treatment of bulimia nervosa and other eating disorders. Recent trials focusing on the abnormal cognitive and emotional aspects of bulimia have reported a remission rate of about 45%, and a relapse rate of about 30% within one year. However, an early CBT trial t...

We have previously shown in two randomized clinical trials that environmental enrichment is capable of ameliorating symptoms of autism spectrum disorder (ASD), and in the present study, we determined whether this therapy could be effective under real-world circumstances. 1,002 children were given daily Sensory Enrichment Therapy, by their parents,...

SÖDERSTEN, P., C. Bergh, M. Leon and M. Zandian. Dopamine and Anorexia Nervosa. NEUROSCI BIOBEHAV REV ab(c) XXX-XXX, 2015. - We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are act...

Diet, exercise, and pharmacological interventions have limited effects in counteracting the worldwide increase in pediatric body weight. Moreover, the promise that individualized drug design will work to induce weight loss appears to be exaggerated. We suggest that the reason for this limited success is that the cause of obesity has been misunderst...

Mandometer versus treatment as usual.

Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment, we attempted to develop a comparable therapy for children with autism. In an initial randomized controlled trial, children with autism who received sensorimotor enrichment at home for 6 months had signifi...

We report the results of a study based on 1,428 patients with eating disorders treated at 6 clinics. These patients were consecutively referred over 18 years and used inpatient and outpatient treatment. The subjects were diagnosed with anorexia nervosa, bulimia nervosa, or an eating disorder not otherwise specified. Patients practiced a normal eati...

Enriched sensorimotor environments enable rodents to compensate for a wide range of neurological challenges, including those induced in animal models of autism. Given the sensorimotor deficits in most children with autism, we attempted to translate that approach to their treatment. In a randomized controlled trial, 3-12 year-old children with autis...

Background Speed of eating, an important aspect of eating behaviour, has recently been related to loss of control of food intake and obesity. Very little time is allocated for lunch at school and thus children may consume food more quickly and food intake may therefore be affected. Study 1 measured the time spent eating lunch in a large group of st...

Statistical analysis.

In an effort to deepen our understanding of mammalian olfactory coding, we have used an objective method to analyze a large set of odorant-evoked activity maps collected systematically across the rat olfactory bulb to determine whether such an approach could identify specific glomerular regions that are activated by related odorants. To that end, w...

We determined whether women and men would alter their pattern of food intake after they had deprived themselves of food. We found that women consumed 12% less food after fasting and that men ate 28% more food after fasting. Serving more food on the test day did not increase food intake of women. Women, who ate at a nearly constant rate (linear eate...

Although it has been shown repeatedly that minimum response times in sensory systems can be quite short, organisms more often continue to respond to sensory stimuli over considerably longer periods of time. The continuing response to sensory stimulation may be a more realistic assessment of natural sensory responses, so we determined for how long a...

To determine how responses evoked by natural odorant mixtures compare to responses evoked by individual odorant chemicals, we mapped 2-deoxyglucose uptake during exposures to vapors arising from a variety of odor objects that may be important to rodents in the wild. We studied 21 distinct natural odor stimuli ranging from possible food sources such...

In previous studies, we mapped glomerular layer 2-deoxyglucose uptake evoked by hundreds of both systematically related and chemically distinct odorants in rat olfactory bulbs. To determine which principles of chemotopic organization revealed in these studies may be more fundamental and which may be more species typical, we now have characterized p...

The coding of olfactory stimuli across a wide range of organisms may rely on fundamentally similar mechanisms in which a complement of specific odorant receptors on olfactory sensory neurons respond differentially to airborne chemicals to initiate the process by which specific odors are perceived. The question that we address in this review is the...

DefinitionA1-A17 is the original designation for separate catecholamine cell groups located in the brain by the use of fluorescent histochemical methods. The numbering began in the medulla and continued into the forebrain. Groups A8-A16 are dopaminergic, and reside primarily in the midbrain and hypothalamus. Another dopaminergic cell type, A17, app...

Systematic mapping studies involving 365 odorant chemicals have shown that glomerular responses in the rat olfactory bulb are organized spatially in patterns that are related to the chemistry of the odorant stimuli. This organization involves the spatial clustering of principal responses to numerous odorants that share key aspects of chemistry such...

In past studies in which we mapped 2-deoxyglucose uptake evoked by systematically different odorant chemicals across the entire rat olfactory bulb, glomerular responses could be related to each odorant's particular oxygen-containing functional group. In the present study we tested whether aliphatic odorants containing two such functional groups (es...

The perceptual quality of odors usually is robust to variability in concentration. However, maps of neural activation across the olfactory bulb glomerular layer are not stable in this respect; rather, glomerular odor representations both broaden and intensify as odorant concentrations are increased. The relative levels of activation among glomeruli...

Many naturally occurring volatile chemicals that are detected through the sense of smell contain unsaturated (double or triple) carbon-carbon bonds. These bonds can affect odors perceived by humans, yet in a prior study of unsaturated hydrocarbons we found only very minor effects of unsaturated bonds. In the present study, we tested the possibility...

Early olfactory experience with a specific odorant enhances the subsequent response of the glomerular layer of the rat olfactory bulb to that same odorant. Because different odorants activate different glomerular layer regions, it seemed plausible that experience with a large number of odorants might result in enhanced glomerular activation during...

Odorants and their perceptions differ along multiple dimensions, requiring that a critical examination of any putative neural code directly assess the multidimensional nature of the encoding process. Previous work has examined simple, systematic odorant differences that, regardless of coding strategy, would be expected to produce simple, systematic...

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. Previously, we demonstrated chemotopically organized and distinct olfactory responses to a homologous series of straight-chained alkanes that consisted of p...

At each stage of odor coding, the olfactory system is divided into anatomical subdivisions that seem to serve distinct functions. Although the olfactory (piriform) cortex has long been known to have anterior and posterior subdivisions with different local architectures (1), the function of these anatomical units has been poorly understood. In this...

As part of our ongoing effort to relate stimulus to response in the olfactory system, we tested the hypothesis that the unique chemical structures and odors of various cyclic odorants would be associated with unique spatial response patterns in the glomerular layer of the rat olfactory bulb. To this end, rats were exposed to sets of odorants, inclu...

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. To understand the processing of pure hydrocarbon structures in this system, we used the [(14)C]2-deoxyglucose method to determine glomerular responses to a...

Our laboratory has characterized spatial patterns of evoked neural activity across the entire glomerular layer of the rat olfactory bulb using primarily aliphatic odorants that differ systematically in functional groups and hydrocarbon structures. To represent more fully the true range of odorant chemistry, we investigated aromatic compounds, which...

Experience with multiple odorants during early postnatal development increases the number of cells in the olfactory bulb of rats. In this study, we asked whether at least part of this increase was due to decreased cell death. We selected 30 natural odorants or synthetic odorant mixtures to stimulate a broad area of the bulb during postnatal days 1-...

The emphasis on the effects of early olfactory restriction has been on the deleterious nature of the consequences of this abnormal early experience. While these effects are certainly present and dramatic, it is also the case that the olfactory system is left fairly intact by this experimental manipulation. If one asks what mechanisms may account fo...

To investigate the effect of odorant hydrocarbon structure on spatial representations in the olfactory bulb systematically, we exposed rats to odorant chemicals possessing one of four different oxygen-containing functional groups on one of five different hydrocarbon backbones. We also used several hydrocarbon odorants lacking other functional group...

Principles of olfactory coding can be clarified by studying the olfactory bulb activity patterns that are evoked by odorants differing systematically in chemical structure. In the present study, we used series of aliphatic esters, ketones, and alcohols (27 odorants total) to determine the effects of functional group position on glomerular-layer act...

To determine whether there is a general strategy used by the olfactory system to represent odorants differing in carbon chain length, rats were exposed to homologous series of straight-chained, saturated aliphatic aldehydes, ethyl esters, acetates, ketones, primary alcohols, and secondary alcohols (32 odorants total). Neural activity across the ent...

There have been a number of recent approaches to the study of olfactory coding, each of which has its advantages and disadvantages. In the present review, we discuss our own work on this topic, which has involved mapping uptake of [14C]2-deoxyglucose across the entire glomerular layer of the rat main olfactory bulb in response to systematically sel...

Insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) are involved in growth of neurons. In the rat olfactory epithelium, we previously showed IGF-IR immunostaining in subsets of olfactory receptor neurons. We now report that IGF-IR staining was heaviest in the olfactory nerve layer of the rat olfactory bulb at embryonic days 18, and 19 an...

When the major response domains in the rat olfactory bulb that are evoked by odorant enantiomers are compared, some of these odorant pairs do not show significantly different activity patterns. Such pairs are not spontaneously discriminated in a behavioral test. We show here that even these similar odorants appear to evoke different activity patter...

In an effort to understand the olfactory code of rats, we collected more than 1,500,000 measurements of glomerular activity in response to 54 odorants selected to provide differences in functional groups and hydrocarbon structure. Each odorant evoked a unique response pattern by differentially stimulating clusters of glomeruli, called modules. Odor...

DNA fragmentation is a key marker of neuronal death during development, yet little is known about the size, pattern or quantities of fragments generated during normal and sensory-deprived development. Since there are few neurons dying at any particular time, it has not been possible to obtain sufficient quantities of material to make such a determi...

Spatial activation patterns within the olfactory bulb are believed to contribute to the neural representation of odorants. In this study, we attempted to predict the perceptions of odorants from their evoked patterns of neural activity in the olfactory bulb. We first describe the glomerular activation patterns evoked by pairs of odorant enantiomers...

Active caspase-3 immunoreactivity was detected in the rat forebrain proliferative regions at birth and remained high in these areas for about 2 weeks, during which period labeled cells were present centroperipherally across the olfactory bulb. By the end of the third postnatal week, only a small number of immunolabeled cells remained in these foreb...

Infant rats are born with a functional olfactory system ([Guthrie & Gall, 1999]). Within the first days of their life they begin to approach the odor of their mother in preference to the odor of a virgin female ([Leon & Moltz, 1971]). These preferences can be seen when the pups are placed in an apparatus designed to allow them to approach one of tw...

Odorants of very different chemical structure that yield the perception of very different odors have long been known to evoke distinct patterns of neural activity in the rat olfactory bulb. This observation suggested that at least one step in the coding of odor information might involve spatial patterns of bulbar activity. Until recently, however,...

Organic acid odorants of differing carbon number produce systematically different spatial patterns of [(14)C]2-deoxyglucose uptake in the glomerular layer of the olfactory bulb. Because increasing carbon number correlates with progressive increases in several molecular features, including hydrophobicity, length, and volume, we determined which of t...

To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural a...

To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural a...

Restriction of early sensory experience alters brain development, but the consequences of reduced experience are particularly dramatic in the olfactory system. In other sensory systems, restricted early experience has not been shown to cause cell death, unless the system has been physically damaged or activity in the sensory nerve has been suppress...

In an effort to understand the means by which similar chemical odorants are encoded in the mammalian brain, we exposed rats to a homologous series of n-aliphatic acids and mapped the response of the entire olfactory bulb glomerular layer by using a high-resolution [14C]-2-deoxyglucose uptake technique. We found that these similar odorants evoked sp...

The emphasis on the effects of early olfactory restriction has been on the deleterious nature of the consequences of this abnormal early experience. While these effects are certainly present and dramatic, it is also the case that the olfactory system is left fairly intact by this experimental manipulation. If one asks what mechanisms may account fo...

In order to determine whether molecular features of odorants are represented spatially in the glomerular layer of the olfactory bulb, we used metabolic mapping of [14C] 2-deoxyglucose uptake in rats exposed to equal vapor concentrations of odorants differing systematically in chemical structure. The odorants were ethyl acetate, ethyl butyrate, isoa...

In this chapter to determine the mechanism or mechanisms underlying the action of olfactory bulb norepinephrine in supporting the acquisition of early olfactory preferences, the researchers determined the spatial localization of β-noradrenergic receptors in the bulb. These receptors localize in both the granule cell layer and the glomerular layer o...

Early olfactory preference training causes both an increased number of juxtaglomerular cells and an increased number of such cells expressing Fos protein. In contrast, there are fewer cells expressing Fos protein in the granule cell layer after training. Here, we report no change in the number or size of granule and mitral cells as a consequence of...

Previous work has shown that odors induce focal uptake of [14C]2-deoxyglucose (2-DG) within the glomerular layer of the main olfactory bulb and that the amount of 2-DG accumulated in these foci increases after early odor learning. To determine if learning-associated changes in 2-DG uptake occur across the entire glomerular layer, we have mapped upt...

Norepinephrine is supplied to both deep and superficial layers of the olfactory bulb through dense projections from the locus coeruleus. Beta-adrenergic receptors are located in nearly all bulb laminae, with high-density foci of beta-1 and beta-2-adrenoceptors present in the glomerular layer. Early olfactory experiences that increase norepinephrine...

Olfactory stimulation evokes a column of activity within the olfactory bulb extending from the glomerular layer to the granule cell layer that can be visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to odors is typified by the activity of relativ...

Synaptophysin is a synaptic vesicle protein that provides a marker of synaptic distribution in the brain. We used synaptophysin immunohistochemistry to detect changes in synaptic distribution in the main olfactory bulb during normal early postnatal development and following early olfactory restriction. Synaptophysin-like immunoreactivity appears ea...

The effect of olfactory deprivation on cellular expression of the Bcl-2 gene in the olfactory bulb of young rats was investigated. Restriction of olfactory stimuli caused an overall increase in Bcl-2 mRNA expression, with increases seen in the lateral aspects of glomerular, external plexiform, mitral and granule cell layers, as well as the medial a...

Young rats exposed to peppermint odor and reinforcing tactile stimulation from postnatal days (PND) 1-18 increase their preference for that odor relative to controls. This early olfactory memory is accompanied by an 80% increase in the density of glomerular-layer cells displaying Fos-like immunoreactivity in response to the learned odor on PND 19....

The density of noradrenergic locus coeruleus projections and beta-adrenergic receptors in the main olfactory bulb of the rat increases with age. Both beta 1- and beta 2-adrenergic receptor subtypes exhibit laminar distributions, with focal regions of high receptor density present within the neuropil of individual glomeruli. Since the first synaptic...

In vivo microdialysis sampling of the olfactory bulbs of awake rats on PND 3 revealed that olfactory stimulation alone does not alter extracellular norepinephrine (NE) levels. Tactile stimulation that is designed to mimic maternal interactions with the young does increase bulb NE and the combined odor and tactile stimulation further increases NE le...

The olfactory bulb exhibits high glycogen phosphorylase activity, the rate-limiting enzyme in the mobilization of glycogen. The bulb also receives dense noradrenergic innervation and noradrenaline is known to stimulate glycogen breakdown. We determined the levels of glycogen in the bulb over the course of development and then determined the ability...

Early sensory stimulation plays a key role in shaping the structure and function of the developing olfactory system. Here, we provide the first direct evidence for apoptotic cell death in the olfactory bulbs of rat pups during normal development and we also demonstrate that olfactory deprivation by unilateral naris occlusion causes a dramatic incre...

Exposure of rats to different odors produces spatially distinct patterns of 14C-2-deoxyglucose uptake (2-DG) in the glomerular layer of the main olfactory bulb. However, lesions of specific regions of the bulb that reliably contain 2-DG foci reportedly do not impair the ability of rats to perform olfactory-guided behaviors, suggesting that the lesi...

Beta-adrenergic stimulation appears to be involved in the establishment of both learned olfactory preferences and functional changes in the olfactory bulb of young rats. We examined the postnatal development of beta-adrenergic receptors within the main olfactory bulb to determine the density and distribution of these receptors. To quantify beta-adr...

Alzheimer's disease may arise from or produce oxidative damage in the brain. To assess the responses of the Alzheimer's brain to possible oxidative challenges, we assayed for glutathione, glucose-6-phosphate dehydrogenase, catalase and superoxide dismutase in twelve regions of Alzheimer's disease and aged control brains. In addition, we determined...

A variety of stimuli can facilitate the acquisition of early olfactory preferences, including milk or sucrose ingestion, warmth, high humidity, tail pressure, and medial forebrain bundle stimulation [1–6]. In addition, a strong or prolonged odor exposure will induce such an olfactory preference in young rats [7]. The relatively nonspecific nature o...

Odor preference training early in life induces anatomical changes in focal areas of the glomerular layer of the rat main olfactory bulb. We examined the associated focal changes in glial cell morphology using immunohistochemistry for glial fibrillary acidic protein (GFAP) and found that the density of immunoreactive processes was higher in glomerul...

Expression of the immediate-early gene c-fos was used to evaluate the coordinate activation of olfactory bulb neurons by brief exposure to specific odors in the alert rat. In situ hybridization to c-fos mRNA was compared to regional increases in 2-deoxy-D-[14C]glucose incorporation in an adjacent section analysis. Levels of c-fos mRNA in olfactory...

Young mammals come to approach the odor of their mother, a response that facilitates their survival during early life. Young rats induce a cascade of events in their mother to induce the emission of her odor. The pups increase circulating prolactin levels, which increases food intake and the emission of large quantities of cecotrophe containing the...

Neonatal rats acquire an olfactory preference following daily exposure to an odor that is accompanied by tactile stimulation. In the present study, we determined the neurobehavioral responses of pups trained and tested with odors of either the same or different concentration. On postnatal day (PND) 1-18, all animals were exposed for 10 min/day to e...

Young rats learn to approach an odor that has been paired with tactile stimulation. This attraction is accompanied by changes in the metabolism and anatomy within the olfactory bulb glomerular layer. In this study, we examined the changes that occur in the olfactory bulb during early olfactory learning, rather than after such pairings have occurred...

The influence of norepinephrine (NE) on the acquisition of a conditioned odor preference and enhanced focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups. On postnatal day (PN) 6, pups were injected with either an NE receptor agonist (isoproterenol), NE receptor antagonist (propranolol or timolol),...

One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unc...

The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfacto...

Unilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. We describe here the effects of early olfactory deprivation on other elem...

Olfactory receptor neurons are a CNS entry point for a wide variety of airborne substances. Therefore, it is probable that detoxification mechanisms are present in these neurons to neutralize such agents. Glutathione (GSH) is an essential component of several detoxification schemes, and in this study we examined the distribution and levels of GSH i...

Young rats learn to approach an odor that had been experienced in the presence of reinforcing tactile stimulation. Subsequent presentation of the conditioned odor also evokes an enhanced focal uptake of 2-deoxyglucose (2-DG) in the glomerular layer of the olfactory bulb, and the glomerular-layer width of such foci increases in conditioned pups. In...

Unilateral olfactory deprivation during postnatal development produces significant structural and neurochemical modifications of the olfactory bulb. In the present report, we describe the functional consequences of such deprivation. Rat pups had a single naris occluded on postnatal day 2 (PN2) to deprive them of early olfactory stimulation. On PN20...

Early unilateral olfactory deprivation produces large structural and neurochemical changes in the olfactory bulb, the first central relay for olfactory information. The functioning of deprived bulbs was examined in the present report by using paired-pulse stimulation of the lateral olfactory tract. Paired-pulse stimulation reflects interactions bet...

Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with ei...

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. T...

An understanding of olfactory system glucose metabolism is necessary for the interpretation of radiolabeled 2-deoxyglucose studies of odor processing since the relationship between glucose uptake and neural activity is based on assumptions regarding cellular glucose utilization. As part of an ongoing study examining divergent pathways of glucose me...

Olfactory nerve input is required for the normal expression of tyrosine hydroxylase (TH) by dopaminergic neurons in the glomerular region of the rodent main olfactory bulb. To determine whether the olfactory nerve exerts a similar influence on neurons in other brain regions, we performed unilateral bulbectomies in rat pups on postnatal day 5-7 and...