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Biomedical subjects

Gordon M Shepherd

Publications and source records attributed to Gordon M Shepherd.

At least 19 recordsLinked to original sources
PubMed2006

Smell images and the flavour system in the human brain.

Flavour perception is one of the most complex of human behaviours. It involves almost all of the senses, particularly the sense of smell, which is involved through odour images generated in the olfactory pathway. In the human brain, the perceptual systems are closely linked to systems for learning, memory, emotion and language, so distributed neural mechanisms contribute to food preference and food cravings. Greater recognition of the role of the brain's flavour system and its connection with eating behaviour is needed for a deeper understanding of why people eat what they do, and to generate better recommendations about diet and nutrition.

Brain↗
PubMed2006

Viral tracing identifies distributed columnar organization in the olfactory bulb.

Olfactory sensory neurons converge onto glomeruli in the olfactory bulb (OB) to form modular information processing units. Similar input modules are organized in translaminar columns for other sensory modalities. It has been less clear in the OB whether the initial modular organization relates to a columnar structure in the deeper layers involved in local circuit processing. To probe synaptic connectivity in the OB, we injected a retrograde-specific strain of the pseudorabies virus into the rat OB and piriform cortex. The viral-staining patterns revealed a striking columnar organization that extended across all layers of the OB from the glomeruli to the deep granule cell layer. We hypothesize that the columns represent an extension of the glomerular unit. Specific patterning was observed, suggesting selective, rather than distance-dependent, center-surround connectivity. The results provide a previously undescribed basis for interpreting the synaptic connections between mitral and granule cells within the context of a columnar organization in the OB and have implications for olfactory coding and network organization.

Animals↗
PubMed2006

Dendritic calcium plateau potentials modulate input-output properties of juxtaglomerular cells in the rat olfactory bulb.

Understanding the intrinsic membrane properties of juxtaglomerular (JG) cells is a necessary step toward understanding the neural basis of olfactory signal processing within the glomeruli. We used patch-clamp recordings and two-photon Ca(2+) imaging in rat olfactory bulb slices to analyze a long-lasting plateau potential generated in JG cells and characterize its functional input-output roles in the glomerular network. The plateau potentials were initially generated by dendritic calcium channels. Bath application of Ni(2+) (250 microM to 1 mM) totally blocked the plateau potential. A local puff of Ni(2+) on JG cell dendrites, but not on the soma, blocked the plateau potentials, indicating the critical contribution of dendritic Ca(2+) channels. Imaging studies with two-photon microscopy showed that a dendritic Ca(2+) increase was always correlated with a dendritic but not a somatic plateau potential. The dendritic Ca(2+) conductance contributed to boosting the initial excitatory postsynaptic potentials (EPSPs) to produce the plateau potential that shunted and reduced the amplitudes of the following EPSPs. This enables the JG cells to act as low-pass filters to convert high-frequency inputs to low-frequency outputs. The low frequency (2.6 +/- 0.8 Hz) of rhythmic plateau potentials appeared to be determined by the intrinsic membrane properties of the JG cell. These properties of the plateau potential may enable JG cells to serve as pacemaker neurons in the synchronization and oscillation of the glomerular network.

Animals↗
PubMed2006

The olfactory glomerulus: a cortical module with specific functions.

The axons of many olfactory receptor cells converge on an individual glomerulus in the olfactory bulb, where they make contacts with the distal dendrites of mitral and tufted cells. Each glomerulus is targeted by olfactory receptor neurons expressing a single type of olfactory receptor protein. The glomerulus provides a unique model in which the function of a cortical module can be unambiguously established. Here we review the increasing evidence that a key functional operation of the glomerulus is to act as a signal-to-noise enhancing device in the processing of sensory input and that this function is critical across vertebrate and invertebrate species for the ability to detect specific odor stimuli within "noisy" odor environments and to carry out discriminations between odor molecules that are structurally closely related.

Animals↗
PubMed2006

Olfactory sensitivity for enantiomers and their racemic mixtures--a comparative study in CD-1 mice and spider monkeys.

Using a conditioning paradigm, the olfactory sensitivity of six CD-1 mice for the enantiomers of carvone and of limonene as well as for their racemic mixtures was investigated. With all six stimuli, the animals significantly discriminated concentrations <or=0.1 ppm (parts per million) from the odorless solvent, and with five of the six stimuli, the best-scoring animals were even able to detect concentrations <or=1 ppb (parts per billion). Five spider monkeys tested in parallel were found to detect the same stimuli at concentrations <1 ppm, and with two of the stimuli, they were also able to discriminate concentrations <1 ppb from the solvent. The results showed 1) both CD-1 mice and spider monkeys to have a well-developed olfactory sensitivity for the stimuli tested, with no systematic difference in performance between species; 2) the effect of chirality on detectability of the enantiomers to be substance specific; 3) no systematic effect of the presence (carvone) or absence (limonene) of a functional carbonyl group on detectability of the enantiomers; and 4) that spider monkeys detected the racemic mixtures of both carvone and limonene at lower concentrations compared to the unmixed compounds, whereas the mice failed to do so. These findings lend support to the growing body of evidence suggesting that between-species comparisons of the relative size of olfactory brain structures do not allow us to reliably predict olfactory sensitivity. As mice and spider monkeys are thought to share a similar number of functional olfactory receptor genes, the findings further suggest that differences in the relative abundance of chiral-specific olfactory receptor types might account for the observed difference in mixture additivity at threshold level between the two species. These threshold data may provide useful information for the choice of adequate stimulus concentrations in electrophysiological or imaging studies of the olfactory system or investigations of the discriminative abilities of mice and spider monkeys.

Animals↗
PubMed2006

Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice.

A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli.

Aldehydes↗
PubMed2006

Dendritic excitability and calcium signalling in the mitral cell distal glomerular tuft.

The processing of odour information starts at the level of the olfactory glomerulus, where the mitral cell distal dendritic tuft not only receives olfactory nerve sensory input but also generates dendrodendritic output to form complicated glomerular synaptic circuits. Analysing the membrane properties and calcium signalling mechanisms in these tiny dendritic branches is crucial for understanding how the glomerular tuft transmits and processes olfactory signals. With the use of two-photon Ca2+ imaging in rat olfactory bulb slices, we found that these distal dendritic branches displayed a significantly larger Ca2+ signal than the soma and primary dendrite trunk. A back-propagating action potential was able to trigger a Ca2+ increase throughout the entire glomerular tuft, indicative of the presence of voltage-gated Ca2+ conductances in all branches at different levels of ramification. In response to a train of action potentials evoked at 60 Hz from the soma, the tuft Ca2+ signal increased linearly with the number of action potentials, suggesting that these glomerular branches were able to support repetitive penetration of Na+ action potentials. When a strong olfactory nerve excitatory input was paired with an inhibition from mitral cell basal dendrites, a small spike-like fast prepotential was revealed at both the soma and distal primary dendrite trunk. Corresponding to this fast prepotential was a Ca2+ increase confined locally within the glomerular tuft. In summary, the mitral cell distal dendritic tuft possesses both Na+ and Ca2+ voltage-dependent conductances which can mediate glomerular Ca2+ responsiveness critical for dendrodendritic output and synaptic plasticity.

Action Potentials↗
PubMed2005

Olfactory sensitivity for aliphatic aldehydes in CD-1 mice.

Using a conditioning paradigm, the olfactory sensitivity of CD-1 mice for a homologous series of aliphatic aldehydes (n-butanal to n-nonanal) was investigated. With all six odorants, the animals significantly discriminated concentrations below 4 ppb (parts per billion) from the odorless solvent, and with n-butanal, n-heptanal, and n-nonanal the best-scoring animals were even able to detect concentrations below 40 ppt (parts per trillion). The results showed (a) CD-1 mice to have a well-developed olfactory sensitivity for aliphatic aldehydes which for the majority of substances is higher than that of other mammalian species, (b) a limited concentration range of about 1 log unit from threshold to near saturation which is similar to that shown at the single receptor cell level, (c) no significant correlation between perceptibility in terms of olfactory detection thresholds and carbon chain length of the aldehydes tested, and (d) no systematic effect of preexposure to an aldehyde on sensitivity. These findings suggest that CD-1 mice are highly sensitive to non-pheromonal odorants that are abundant in plant odors. Further, the results demonstrate that sensitivity for members of a homologous series of substances is not a simple function of vapor pressure as threshold values did not correlate with molecular weight. These threshold data may provide useful information for the choice of adequate stimulus concentrations in electrophysiological or imaging studies of the olfactory system or investigations of the discriminative abilities of the mouse.

Aldehydes↗
PubMed2005

Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones.

It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high-resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2-Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed.

Animals↗
PubMed2005

Perception without a thalamus how does olfaction do it?

The olfactory system has generated considerable interest in recent years, mainly focused on receptor genes and early olfactory processing. In this issue of Neuron, Mori et al. focus centrally, providing evidence for slow- and fast-wave states in olfactory cortex that appear to gate the inflow of information underlying conscious smell perception.

Olfactory Bulb↗
PubMed2005

Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation.

The first-order sensory relay for olfactory processing, the main olfactory bulb (MOB), retains the ability to acquire new interneurons throughout life. It is therefore a particularly appropriate region for studying the role of experience in sculpting neuronal networks. We found that nostril closure decreased the number of newborn granule cells in the MOB, the complexity of their dendritic arborization, and their spine density, without affecting the preexisting population of granule cells. Accordingly, the frequency of miniature synaptic inhibitory events received by mitral cells was reduced. However, due to a compensatory increase in newborn granule cell excitability, action potential-dependent GABA release was dramatically enhanced, thus counteracting the reduction in spine density and leading to an unaltered synchronization of mitral cell firing activity. Together, this study reveals a unique form of adaptive response brought about exclusively by the cohort of newborn cells and used to maintain normal functioning of the MOB.

Animals↗
PubMed2005

Transient and persistent dendritic spines in the neocortex in vivo.

Dendritic spines were imaged over days to months in the apical tufts of neocortical pyramidal neurons (layers 5 and 2/3) in vivo. A fraction of thin spines appeared and disappeared over a few days, while most thick spines persisted for months. In the somatosensory cortex, from postnatal day (PND) 16 to PND 25 spine retractions exceeded additions, resulting in a net loss of spines. The fraction of persistent spines (lifetime > or = 8 days) grew gradually during development and into adulthood (PND 16-25, 35%; PND 35-80, 54%; PND 80-120, 66%; PND 175-225, 73%), providing evidence that synaptic circuits continue to stabilize even in the adult brain, long after the closure of known critical periods. In 6-month-old mice, spines turn over more slowly in visual compared to somatosensory cortex, possibly reflecting differences in the capacity for experience-dependent plasticity in these brain regions.

Aging↗
PubMed2005

Opinion: an integrated approach to classifying neuronal phenotypes.

Characterizing the functional phenotypes of neurons is essential for understanding how genotypes can be related to the neural basis of behaviour. Traditional classifications of neurons by single features (such as morphology or firing behaviour) are increasingly inadequate for reflecting functional phenotypes, as they do not integrate functions across different neuronal types. Here, we describe a set of rules for identifying and predicting functional phenotypes that combine morphology, intrinsic ion channel species and their distributions in dendrites, and functional properties. This more comprehensive neuronal classification should be an improvement on traditional classifications for relating genotype to functional phenotype.

Animals↗
PubMed2004

High-throughput microarray detection of olfactory receptor gene expression in the mouse.

The large number of olfactory receptor genes necessitates high throughput methods to analyze their expression patterns. We have therefore designed a high-density oligonucleotide array containing all known mouse olfactory receptor (OR) and V1R vomeronasal receptor genes. This custom array detected a large number of receptor genes, demonstrating specific expression in the olfactory sensory epithelium for approximately 800 OR genes previously designated as ORs based solely on genomic sequences. The array also enabled us to monitor the spatial and temporal distribution of gene expression for the entire OR family. Interestingly, OR genes showing spatially segregated expression patterns were also segregated on the chromosomes. This correlation between genomic location and spatial expression provides unique insights about the regulation of this large family of genes.

Age Factors↗