Static magnetic field modulates rhythmic activities of a cluster of large local interneurons in Drosophila antennal lobe.

With the development of superconducting magnets, the chances of exposure to intense static magnetic fields (SMFs) have increased. Therefore, safety concerns related to magnetic field exposure need to be studied, especially the effects of magnetic field exposure on the central nervous system. Only a limited number of studies prove a direct connection between magnetic fields and electrophysiological signal processing. Here we described a cluster of large local interneurons (LNs) located laterally to each antennal lobe of Drosophila melanogaster, which exhibit extensive arborizations throughout the whole antennal lobe. Dual recordings showed that these large LNs demonstrated rhythmic spontaneous activities that correlated with other LNs and projection neurons (PNs) in the olfactory circuit. The results suggest that 3.0-T SMF can interfere with the properties of the action potential, rhythmic spontaneous activities of large LNs, and correlated activity in pairs of ipsilateral large LN/LN in the olfactory circuit. This indicates that Drosophila can be an ideal intact neural circuit model and that the activities of the olfactory circuit can be used to evaluate the effects of magnetic field stimulations.

Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

BACKGROUND: In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. CONCLUSION/SIGNIFICANCE: These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

Behavioral state regulation of dendrodendritic synaptic inhibition in the olfactory bulb.

Behavioral states regulate how information is processed in local neuronal circuits. Here, we asked whether dendrodendritic synaptic interactions in the olfactory bulb vary with brain and behavioral states. To examine the state-dependent change of the dendrodendritic synaptic transmission, we monitored changes in field potential responses in the olfactory bulb of urethane-anesthetized and freely behaving rats. In urethane-anesthetized rats, granule-to-mitral dendrodendritic synaptic inhibition was larger and longer when slow waves were present in the electroencephalogram (slow-wave state) than during the fast-wave state. The state-dependent alternating change in the granule-to-mitral inhibition was regulated by the cholinergic system. In addition, the frequency of the spontaneous oscillatory activity of local field potentials and periodic discharges of mitral cells in the olfactory bulb shifted in synchrony with shifts in the neocortical brain state. Freely behaving rats showed multilevel changes in dendrodendritic synaptic inhibition that corresponded to diverse behavioral states; the inhibition was the largest during slow-wave sleep state, and successively smaller during light sleep, awake immobility, and awake moving states. These results provide evidence that behavioral state-dependent global changes in cholinergic tone modulate dendrodendritic synaptic inhibition and the information processing mode in the olfactory bulb.

Effects of radiotherapy on olfactory function.

BACKGROUND AND PURPOSE: Changes in olfactory function have been reported in patients receiving significant doses of radiation to the olfactory epithelium. Aim of this study was to investigate severity and time course of changes in olfactory function in patients irradiated for tumours of the head and neck region. MATERIAL AND METHODS: Forty-four patients receiving radiotherapy (RT) for tumours in the area of the head and neck participated (16 women, 28 men; age 11-81 y; mean 55 y). Olfactory function was measured before and bi-weekly during RT for 6 weeks. A subgroup (25 patients) was followed for 12 months. Patients were divided into two groups according to the dose to the olfactory epithelium. Twenty-two patients ('OLF group') had radiation doses to the olfactory epithelium between 23.7 and 79.5 Gy (median 62.2 Gy). In the 22 patients of the 'non-OLF group' the dose applied to the olfactory epithelium was significantly lower (2.9-11.1 Gy, median 5.9 Gy). Total tumour dose (30-76.8 Gy), age, sex distribution, and baseline chemosensory function were not significantly different between groups. Testing was performed for odour identification, odour discrimination, and olfactory thresholds. RESULTS: Odour discrimination, but not odour identification or odour threshold, was significantly decreased 2-6 weeks after begin of therapy in the OLF group. In addition, a significant effect of the radiation dose was observed for odour discrimination. More than 6 months after therapy, OLF group patients had significantly lower odour identification scores compared to the non-OLF group. CONCLUSION: As indicated through the non-significant change of olfactory thresholds, the olfactory epithelium is relatively resistant against effects of radiation. It is hypothesized that RT has additional effects on the olfactory bulb/orbitofrontal cortex responsible for the observed changes of suprathreshold olfactory function.

Ontogeny of cortical synaptic depression underlying olfactory sensory gating in the rat.

Sensory gating is the ability to filter irrelevant or redundant sensory input and is a critical function of all sensory systems that allows efficient processing of important stimuli. The present results demonstrate that a form of activity-dependent synaptic depression recently found to be involved in both cortical and behavioral olfactory sensory gating, is functional by at least the first postnatal week in the rat piriform cortex, and shares a common metabotropic glutamate receptor mechanism.

5-Hydroxytryptamine action in the rat olfactory bulb: in vitro electrophysiological patch-clamp recordings of juxtaglomerular and mitral cells.

The olfactory bulb, first relay of olfactory pathways, is densely innervated by serotoninergic centrifugal fibers originating from the raphe nuclei. Although serotonin innervation was reported to be involved in olfactory learning in mammals, the action of this neurotransmitter on its putative cellular targets has been never described through unitary recordings. This lack of data initiated the present study where the effects of 5HT on juxtaglomerular and mitral cells are analyzed using whole-cell recordings on olfactory bulb slices. Serotonin depolarizes 34% of 525 JG cells. A multivariate statistical analysis of juxtaglomerular cells characteristics shows that the serotonin responsive cell group can be individualized regarding their tonic discharge-mode in response to a direct current injection, their lower expression of hyperpolarization-activated cation current and their low membrane capacities. The use of ion channel blockers and ramp voltage protocol indicate that serotoninergic depolarization of juxtaglomerular cells may be due to a nonselective cation current with a reversal potential of -44 mV. Pharmacological tests with serotonin receptor antagonists and agonists reveal that 5HT action on juxtaglomerular cells would be mainly mediated by 5HT2C receptors. In mitral cells, serotonin acts on 49.1% of the 242 tested cells, inducing two types of responses. A first subset of mitral cells (26.8%, n=65) were hyperpolarized by serotonin. This response would be indirect and mediated by action of GABA on GABAA receptors since it was antagonized by bicuculline. The involved GABAergic neurons are hypothesized to be juxtaglomerular and granular cells, on which serotonin would act mainly via 5HT2C and via 5HT2A receptors respectively. The second subset of mitral cells (22.3%, n=54) were directly depolarized by serotonin acting through 5HT2A receptors. Our data on serotonin action on juxtaglomerular cells and mitral cells reveal a part of functional mechanisms whereby serotonin can act on olfactory bulb network. This is expected to enrich the understanding of its determining role in olfactory learning.

Changes in olfactory inputs modify the energy balance response to short days in male gray mouse lemurs.

The role of olfaction/olfactory cues on photoperiodic responses was assessed in Malagasy primate, the gray mouse lemur. When exposed to short photoperiod (SP), this primate demonstrates rapid changes in energy balance as adaptive anticipatory response for winter survival. To follow early changes induced by SP exposure, body mass, food intake, resting metabolism (RMR) and free thyroxin levels in plasma (T4) were measured in males abruptly transferred to SP: six intact males (controls), eight males that underwent bilateral olfactory removal (BOX) and eight males exposed to male urinary cues (U-exposed). To assess the effect of SP exposure, two other groups were maintained for 6 weeks under LP: six controls and six BOX males. Whereas all studied parameters remained constant in controls and BOX males maintained under LP, exposure to SP led to different responses according to groups. In controls, SP exposure led to a regular increase in body mass and after 4 weeks under SP, plasma T4 levels, food consumption and RMR significantly decreased. Even if BOX males demonstrated hyperphagic patterns regardless of the photoperiod, an increase in body mass was also induced by SP exposure but without changes in RMR or food intake that were body mass-dependent. In U-exposed males, body mass gain was significantly reduced while food intake and RMR remained high. In both BOX and U-exposed males, SP exposure led to a transient but high increase in T4 levels compared to controls. These results suggest that olfaction/olfactory cues may delay the SP-mediated changes in energy balance.

Polysynaptic olfactory pathway to the ipsi- and contralateral entorhinal cortex mediated via the hippocampus.

Interactions between olfactory cortices and the hippocampus support sensory discrimination and spatial learning functions. The olfactory input accesses the hippocampal formation via a polysynaptic pathway mediated by the lateral and rostral entorhinal cortex (EC). We recently demonstrated that following repetitive stimulation of the lateral olfactory tract (LOT) at 2-8 Hz, a delayed response (onset at circa 60 ms) was evoked in the caudal portion of the EC, identified as medial EC, that does not receive a direct olfactory input. By performing simultaneous laminar profile analysis in the EC and in different hippocampal subfields, we conclusively demonstrate that the delayed EC response evoked by repetitive ipsilateral LOT stimulation is headed by the sequential activation of the dentate gyrus and the CA3/CA1 subfields in the septal and temporal hippocampus. Repetitive stimulation of the contralateral LOT also induced an EC response that peaked at 76.28+/-2.42 ms (n=15). Current source density analysis and time-delay analysis of simultaneous field potential laminar profiles performed from the EC and from DG, CA3 and CA1 hippocampal subfields suggested that the contralateral EC response is mainly carried by an intrahippocampal CA3-CA3 commissural pathway. Contralateral LOT stimulation also induced a later EC component (delay >100 ms) generated in the superficial layers, mediated either by local associative interactions or by extrahippocampal circuits. The opportunity to activate the ipsi- and contralateral olfactory pathways in the same experiment and to record field potentials profiles simultaneously in different structures of both hemispheres in the isolated guinea-pig brain confirms that this preparation is unique and is particularly suitable for investigating the system physiology of the limbic region. The present study demonstrates that patterned stimulation of the olfactory input that mimics sniffing patterns during odor discrimination induces a diffuse activation of both ipsi- and contralateral hippocampi and ECs. The findings contribute to the understanding the physiological mechanisms that underlie associative interactions between olfactory and non-olfactory cortical inputs converging into the mesial temporal region.

Representation of binary pheromone blends by glomerulus-specific olfactory projection neurons.

An outstanding challenge in olfactory neurobiology is to explain how glomerular networks encode information about stimulus mixtures, which are typical of natural olfactory stimuli. In the moth Manduca sexta, a species-specific blend of two sex-pheromone components is required for reproductive signaling. Each component stimulates a different population of olfactory receptor cells that in turn target two identified glomeruli in the macroglomerular complex of the male's antennal lobe. Using intracellular recording and staining, we examined how responses of projection neurons innervating these glomeruli are modulated by changes in the level and ratio of the two essential components in stimulus blends. Compared to projection neurons specific for one component, projection neurons that integrated information about the blend (received excitatory input from one component and inhibitory input from the other) showed enhanced ability to track a train of stimulus pulses. The precision of stimulus-pulse tracking was furthermore optimized at a synthetic blend ratio that mimics the physiological response to an extract of the female's pheromone gland. Optimal responsiveness of a projection neuron to repetitive stimulus pulses therefore appears to depend not only on stimulus intensity but also on the relative strength of the two opposing synaptic inputs that are integrated by macroglomerular complex projection neurons.

Postirradiation volatile secretions of mice: syngeneic and allogeneic immune and behavioral effects.

The immune response in immunologically and olfactorily high- and low-reactive CBA and C57Bl/6 mice is almost similarly decreased after exposure to volatile secretions of syngeneic animals exposed to ionizing radiation in a dose of 4 Gy. In the preference/avoidance test intact animals prefer secretions of irradiated syngeneic and allogeneic animals to those of intact animals, while without irradiation animals of both strains prefer syngeneic secretions. C57Bl/6 mice differ from CBA animals by lower sensitivity.

Olfactory sensations produced by high-energy photon irradiation of the olfactory receptor mucosa in humans.

During irradiation of volumes that incorporate the olfactory system, a proportion of patients have complained of a pungent smell. A retrospective study was carried out to determine the prevalence of this side-effect. A questionnaire was sent to 40 patients whose treatment volumes included the olfactory region and also to a control group treated away from this region. The irradiated tumor volumes included the frontal lobe, whole brain, nasopharynx, pituitary fossa, and maxillary antrum. Of the 25 patients who replied, 60% experienced odorous symptoms during irradiation. They described the odor as unpleasant and consistent with ozone. Stimulation of olfactory receptors is considered to be caused by the radiochemical formation of ozone and free radicals in the mucus overlying the olfactory mucosa.

Effects of hydroxyurea parallel the effects of radiation in developing olfactory glomeruli in insects.

Previous observations (Oland and Tolbert: J. Comp. Neurol. 255:196-207, '87, Soc. Neurosci. Abstr. 13:1144, '87; Oland et al.: J. Neurosci. 8:353-367, '88) have provided evidence that the afferent-axon-induced development of synaptic glomeruli in the antennal lobe of the moth Manduca sexta depends upon an interaction between ingrowing sensory axons and the glial cells of the antennal lobe. In order to differentiate between the roles of glial cells and of afferent axons on the partitioning of the lobe into glomeruli, we have used the antimitotic agent hydroxyurea to produce lobes deficient in glial cells but retaining sensory input. The resulting lobes were analyzed in the light and electron microscopes, and the integrity of their antennal input was evaluated by examining the gross and microscopic structure of the antennae, the number of antennal afferent axons, and electroantennogram responses to odors. Our results with hydroxyurea show that in treated animals with adequate antennal input the degree to which the antennal-lobe neuropil becomes glomerular varies with the number of glial cells remaining in the lobe; when less than approximately one-quarter of the normal glial complement is present, glomeruli do not develop at all. These experiments complement and extend previous experiments in which the number of glial cells was reduced with radiation (Oland et al.: J. Neurosci. 8:353-367, '88). The fact that the present results mimic the previous results with radiation strongly suggest that glial cells do mediate the afferent-axon-induced formation of olfactory glomeruli in the moth.