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A systems perspective on early olfactory coding.

This review critically examines neuronal coding strategies and how they might apply to olfactory processing. Basic notions such as identity, spatial, temporal, and correlation codes are defined and different perspectives are brought to the study of neural codes. Odors as physical stimuli and their processing by the early olfactory system, one or two synapses away from the receptors, are discussed. Finally, the concept of lateral inhibition, as usually understood and applied to odor coding by mitral (or equivalent) cells, is challenged and extended to a broader context, possibly more appropriate for olfactory processing.

Animals↗

Dynamic optimization of odor representations by slow temporal patterning of mitral cell activity.

Mitral cells (MCs) in the olfactory bulb (OB) respond to odors with slow temporal firing patterns. The representation of each odor by activity patterns across the MC population thus changes continuously throughout a stimulus, in an odor-specific manner. In the zebrafish OB, we found that this distributed temporal patterning progressively reduced the similarity between ensemble representations of related odors, thereby making each odor's representation more specific over time. The tuning of individual MCs was not sharpened during this process. Hence, the individual responses of MCs did not become more specific, but the odor-coding MC assemblies changed such that their overlap decreased. This optimization of ensemble representations did not occur among olfactory afferents but resulted from OB circuit dynamics. Time can therefore gradually optimize stimulus representations in a sensory network.

Amino Acids↗

In vivo calcium imaging of brain activity in Drosophila by transgenic cameleon expression.

Various genetically encoded fluorescent sensors that monitor changes in intracellular calcium concentration have been developed over the last few years. The ability to target these calcium indicators to cells and structures of interest makes them valuable tools for diverse applications and gives them distinct advantages over conventional fluorescent dyes in transgenically tractable organisms. In particular, the cameleon calcium sensors have been used successfully in a number of applications. For example, we use cameleon-2.1 to monitor in vivo brain activity in Drosophila. However, using cameleons to image intracellular calcium concentration changes in vivo is still evolving and is by no means a standard technique. Experimental details and "tricks" for dealing with equipment, techniques, and data evaluation are still restricted to a few laboratories. In this protocol for calcium imaging in Drosophila brain using cameleon-2.1, we provide guidelines to the basic principles of this novel technique in Drosophila neuroscience and, more generally, to the broad field of signal transduction research.

Animals↗

The limbic system and the localisation of herpes simplex encephalitis.

The selective destruction of temporal and frontal lobe structures by herpes simplex encephalitis has been explained as a consequence of the proximity of those regions to the point of entry of the virus in the encephalon, through olfactory pathways or meningeal branches of the trigeminal nerves. An alternative hypothesis is presented: that the encephalitis is due to a special affinity of the herpes simplex Type 1 virus for the limbic cortices, that is, that distinctive neuroanatomical, neurochemical and neuroimmunological properties of those cortices permit the virus to manifest its destructive behaviour, regardless of the route of entry to the CNS, possibly during altered immunological states. The study of the neurochemical and neuroimmunological properties of the limbic cortices may be a useful approach to the enigma of why and when herpes simplex Type 1 causes encephalitis.

Animals↗

Information coding in the vertebrate olfactory system.

The olfactory systems of vertebrates are able to discriminate a vast array of structurally diverse odorants. This perceptual acuity derives from a series of information-processing events that occur within distinct neural structures through which olfactory sensory information flows. This review discusses current knowledge concerning the mechanisms by which olfactory stimuli are initially detected and transduced into electrical signals that are transmitted to the olfactory bulb of the brain. It also reviews how information may initially be organized, or encoded, and then reorganized as it flows through the system.

Amino Acid Sequence↗

Distributed and concentration-invariant spatial representations of odorants by receptor neuron input to the turtle olfactory bulb.

We sought to characterize how odorants are represented at the level of afferent input to the olfactory bulb of the box turtle, a terrestrial reptile that, like mammals, detects airborne odorants. Using methods developed first in zebrafish, we selectively labeled olfactory receptor neurons with Calcium Green-1 dextran and imaged odorant-evoked input to glomeruli in vivo. Odorant representations were imaged at a glomerular level of resolution over a portion of the dorsal olfactory bulb and at a regional level of resolution over the entire dorsal surface. We report two new findings. First, even at low concentrations, odorants typically elicited input to a large fraction of all imaged glomeruli. Second, while the amplitude of the odorant-evoked input to glomeruli was concentration dependent, the relative pattern of input to the bulb changed only slightly over a concentration range of up to three log units. These results suggest the hypothesis that odorant representations in the turtle involve differential levels of input to many glomeruli, and that detecting relative patterns of distributed glomerular activation may be an important strategy for encoding odor quality independent of intensity.

Animals↗

Evidence for glutamate as the olfactory receptor cell neurotransmitter.

1. Synaptic transmission between olfactory receptor neurons and mitral/tufted cells was examined using a whole-cell recording technique in a hemisected preparation of the turtle olfactory bulb. To determine the olfactory receptor neuron transmitter, we isolated components of the synaptic response of mitral/tufted cells to olfactory nerve stimulation using postsynaptic receptor antagonists. 2. Low-intensity stimulation of the olfactory nerve evoked monosynaptic excitatory postsynaptic potentials in mitral/tufted cells that consisted of a rapid and prolonged depolarization with little contribution from other bulb neurons. The exogenous application of glutamate mimicked the response of mitral/tufted cells to olfactory nerve stimulation. 3. Olfactory nerve stimulation evoked in mitral/tufted cells a two component response that was reversibly blocked by glutamate receptor antagonists. The first, a rapid depolarization of short duration, was sensitive to the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX); the second, a depolarization of slower onset but longer duration, was sensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5). When DNQX and AP5 were both present the postsynaptic response was completely abolished. These results strongly support the notion that glutamate is the neurotransmitter at the olfactory nerve to mitral/tufted cell synapse.

Animals↗

Developmental changes in the density of ionic currents in antennal-lobe neurons of the sphinx moth, Manduca sexta.

Early in metamorphic adult development, action potentials elicited from Manduca sexta antennal lobe neurons are small in amplitude, long in duration, and calcium dependent. As development proceeds, the action potential waveform becomes larger in amplitude, shorter in duration, and increasingly sodium dependent. Whole cell voltage-clamp analysis of Manduca antennal-lobe neurons in vitro has been used to identify voltage-activated currents that contribute to developmental changes in the electrical excitability of these cells. Proximal Branching neurons [putative projection (output) neurons] and Rick Rack neurons (putative local antennal-lobe interneurons) are examined in detail early (pupal stage 5) and late (pupal stage 14) in adult metamorphosis. In both cell types, four voltage-gated and two calcium-dependent ionic currents have been identified. Cell-type-specific changes in the density of sodium, calcium, and potassium currents correlate temporally with changes in cell excitability and spike waveform. Developmental changes in ionic current profiles are accompanied also by the emergence of cell-type-specific response characteristics in the cells. Together with the accompanying paper, this study provides an important foundation for examining the impact of developmental changes in electrical excitability on the growth, electrical properties and connectivity of neurons in central olfactory pathways of the moth.

Action Potentials↗

Olfaction: from odorant molecules to the olfactory cortex.

How do we smell? Our knowledge of how odor information from the environment is perceived has greatly advanced since the discovery of approximately 1,000 genes for odorant receptors in the mammalian genome. From the combination of molecular-genetic, electrophysiological, and optical imaging studies a better understanding of how we smell is emerging.

Animals↗

The antennal lobe of orthoptera - anatomy and evolution.

The first odor-processing neuropils of insects comprise glomeruli, islets of neuropil, that are supplied by olfactory receptor neurons and give rise to efferent axons to higher brain centers. Glomeruli size and organization varies in a taxon-specific manner across the Insecta, suggesting possible correlates between their organization and chemosensory behaviors in different insect groups. Comparative studies of antennal lobe glomeruli within the Orthoptera have been used to infer how the various taxon-specific arrangements of odorant-processing structures (glomeruli) might have evolved. The cellular arrangements in glomeruli have been surveyed using anterograde filling and Golgi impregnation of antennal receptor neurons projecting to the antennal lobe in Stenopelmatidae, Tettigoniidae, Gryllidae, Tetrigidae and Acrididae. These taxa, which represent the two sub-orders of Orthoptera, reveal a high correlation between the neural architecture of the glomeruli and structures within the glomeruli. Using a recent molecular phylogeny of the Orthoptera we have mapped the occurrence of glomerular characteristics to infer the evolution of antennal lobe structures in orthopterans. The functional implications of these results are discussed.

Animals↗

Inheritance of olfactory preferences II. Olfactory receptor neuron responses from Heliothis subflexa x Heliothis virescens hybrid male moths.

Single-cell electrophysiological recordings were obtained from olfactory receptor neurons (ORNs) in sensilla trichodea on male antennae of hybrids formed mainly by crossing female Heliothis subflexa with male Heliothis virescens ('SV hybrids'). We recorded from the A-, B-, and C-type sensilla trichodea, with the latter two types housing ORNs exhibiting response profiles to different pheromone components that we had previously found to be characteristic for each species. For both the B- and the C-type SV hybrid sensilla, most of the ORNs exhibited a spike amplitude and ORN co-compartmentalization within sensilla that more strongly resembled the ORNs of parental H. subflexa rather than those of H. virescens. The overall mean dose-response profiles of the ORNs in hybrid C- and B-type sensilla were intermediate between those of the H. virescens and H. subflexa parental type ORNs. However, not all hybrid ORNs were intermediate in their tuning spectra, but rather ranged from those that closely resembled H. subflexa or H. virescens parental types to those that were intermediate, even on the same antenna. The most noteworthy shift in ORN responsiveness in hybrid males was an overall increase in sensitivity to Z9-14:Ald exhibited by Z9-16:Ald-responsive ORNs. Heightened cross-responsiveness to Z9-14:Ald by hybrid ORNs correlates well with observed behavioral cross-responsiveness of hybrids in which Z9-14:Ald could substitute for Z9-16:Ald in the pheromone blend, a behavior not observed in parental types. The hybrid ORN shifts involving greater sensitivity to Z9- 14:Ald also correlate well with studies of hybrid male antennal lobe interneurons that exhibited a shift toward greater cross-responsiveness to Z9-14:Ald and Z9- 16:Ald. We propose that the differences between parental H. virescens, H. subflexa, and SV hybrid male pheromone ORN responsiveness to Z9-16:Ald and Z9-14:Ald are most logically explained by an increased or decreased co-expression of two different odorant receptors for each of these compounds on the same ORN.

Analysis of Variance↗

Inheritance of olfactory preferences III. Processing of pheromonal signals in the antennal lobe of Heliothis subflexa x Heliothis virescens hybrid male moths.

Pheromone-responsive olfactory interneurons were studied to determine the extent to which their physiological and morphological properties complemented the behavior and peripheral olfactory neurobiology observed in hybrid male moths created by interbreeding two species of heliothine moth, Heliothis virescens and Heliothis subflexa. Complete recordings were made from a total of 33 neurons, and 16 projection neurons (PNs) were subsequently stained with a fluorescent dye. Stained PNs tuned to pheromonal odorants had dendritic arborizations restricted to one of four olfactory glomeruli that together constituted the macroglomerular complex (MGC). As in parental males, PNs tuned to (Z)-11-hexadecenal always had an arbor in the cumulus, the largest of the MGC glomeruli. Previous neurophysiological investigations revealed that PNs with dendritic arbors restricted to the dorso-medial glomerulus (DM) of the MGC responded specifically to either (Z)-9-tetradecenal (Z9-14:Ald; H. virescens males) or (Z)-9-hexadecenal (Z9-16:Ald; H. subflexa males). Hybrid males, which responded equally well in wind tunnel tests to blends containing either Z9-14:Ald or Z9-16:Ald, had DM PNs that responded to both odorants. PNs specific for a third compound, (Z)-11-hexadecenol, required by hybrid males for behavioral activity were localized to the antero-medial MGC glomerulus (AM). Thus, neuronal activity across the cumulus, DM and AM glomeruli represented an attractive blend in hybrid males. Neurons tuned to (Z)-11-hexadecenyl acetate and Z9-14:Ald were restricted to a fourth, ventro-medial glomerulus. The across-glomerular pattern of activity associated with attractive pheromone blends was most similar to that of H. subflexa males, signifying a dominant effect of H. subflexa genes. These results indicate that the behavioral phenotype of hybrid males can be linked to underlying central olfactory characteristics.

Analysis of Variance↗

Anatomy and forebrain projections of the olfactory and vomeronasal organs in axolotls (Ambystoma mexicanum).

We examined the anatomy of the nasal cavity and forebrain in the axolotl (Ambystoma mexicanum) to determine whether the olfactory and vomeronasal systems are present in this neotenic aquatic salamander. The current study was motivated by two considerations: (a) little is known of the anatomy of the vomeronasal system in aquatic vertebrates, and (b) the presence of both olfactory and vomeronasal systems in larval amphibians has broad implications for the evaluation of these systems in vertebrates. From cresyl-violet-stained sections of snouts we determined that the nasal cavity of axolotls is much like that of terrestrial salamanders. The main chamber of the nasal cavity contains an olfactory epithelium, which is confined to grooves between longitudinal ridges of connective tissue covered in a nonsensory epithelium which lacks goblet cells. Using transmission electron microscopy, we found morphologically distinct olfactory receptor cells: many receptor cells terminate in microvillar dendrites, and fewer terminate in motile cilia with the 9 + 2 microtubule array typical of vertebrate olfactory receptor cells. The ciliated and microvillar cells occur in clusters with little intermingling. Horseradish peroxidase labeling revealed that axons of the olfactory receptor cells terminate in large glomeruli in the main olfactory bulb at the rostral end of the telencephalon. Lateral to the main chamber of the nasal cavity is a diverticulum that is entirely lined with a vomeronasal epithelium containing basal cells, microvillar receptor cells, sustentacular cells that lack specialized processes on the apical surface, and large ciliated cells that may function to move fluid across the vomeronasal epithelium. Unlike the olfactory epithelium, the vomeronasal epithelium lacks Bowman's glands. Using horseradish peroxidase, we determined that the axons of the vomeronasal receptor cells project to the accessory olfactory bulb, a distinct structure dorsal and caudal to the main olfactory bulb. The presence of both olfactory and vomeronasal systems in axolotls and other neotenic salamanders implies that both systems are pleiomorphic in larval amphibians; we therefore suggest that the vomeronasal system may not have originated as an adaptation to terrestrial life.

Ambystoma mexicanum↗

Distribution of carnosine-like immunoreactivity in the brain of the crested newt.

The distribution of the dipeptide carnosine was studied in the brain of the crested newt, Triturus carnifex, with immunohistochemical methods. Carnosine-like immunoreactivity (IR) is present in the cell bodies and processes of several areas of the central nervous system: in the telencephalon (especially in the medial pallium), in the diencephalon (pineal organ, thalamus, and hypothalamus), in the mesencephalon (optic tectum and tegmentum), and in the rhombencephalon (cerebellum, raphe region, and octavolateralis area). Double-labelling experiments show that carnosine IR is colocalized with tyrosine hydroxylase and neuropeptide Y IR in a few cells. Histochemical staining for heavy metals, the TIMM method, reveals that carnosine IR and TIMM labelling overlap in the medial pallium. These data indicate two primary conclusions: (a) In the crested newt brain, in contrast to those of mammals and birds, carnosine IR is not associated with glial cells but with neurons. Furthermore, carnosine is absent from the primary olfactory pathway in newts. (b) In the medial pallium of the crested newt, carnosine IR reliably identifies a population of neurons.

Animals↗

Bilateral sensory neglect following midsagittal reticular formation lesions in cats.

We have observed that midsagittal reticular formation lesions in cats produce bilateral deficits in attention to and localization of various sensory modalities. To correlate these changes with previously reported changes following lesions in other areas of the brain, we propose the existence of two interdependent inhibitory pathways which originate in the frontal lobes.

Animals↗