Odours are represented by speci®c ensembles of activated glomeruli in a combinatorial manner within the olfactory bulb of vertebrates or the antennal lobe (AL) of insects. Here, we optically measured glomerular calcium activities in vivo in the honeybee Apis mellifera during olfactory stimulation with 36 pure chemicals differing systematically in carbon chain length (C-5±10) and functional group (aldehyde, ketone, alcohol, carboxylic acid and alkane). We show their glomerular representations in 38 morphologically identi®ed glomeruli out of the honeybee's 160. We measured the molecular receptive range of identi®ed glomeruli averaging up to 21 individuals. Of the 38 glomeruli measured, 23 show maximal activity in a speci®c range of chain length. Glomeruli preferentially responding to a functional group are also always broadly tuned to particular chain lengths. Furthermore, glomeruli with similar response spectra are often direct neighbours. The results allow conclusions about the interactions between olfactory receptors and odour molecules, and about the AL network.

Odors are coded by glomerular activity patterns in the insect antennal lobe (AL) and in the mammalian olfactory bulb. We measured glomerular responses to 30 different odors in the AL of honeybees using calcium-sensitive dyes. By subsequently staining glomeruli and identifying individual glomerular outlines, we were able to compare the patterns between animals. Regardless of whether the odors were mixtures or pure substances, environmental odors or pheromones, their representations were highly conserved among individuals. Therefore, it may be possible to create a functional atlas of the AL in which particular molecular receptive ranges are attributed to each glomerulus.

Microglia are the resident macrophage population of the CNS and are considered its major immunocompetent elements. They are activated by any type of brain pathology and can migrate to the lesion site. The chemokine CXCL10 is expressed in neurons in response to brain injury and is a signaling candidate for activating microglia and directing them to the lesion site. We recently identified CXCR3, the corresponding receptor for CXCL10, in microglia and demonstrated that this receptor system controls microglial migration. We have now tested the impact of CXCR3 signaling on cellular responses after entorhinal cortex lesion. In wild-type mice, microglia migrate within the first 3 d after lesion into the zone of axonal degeneration, where 8 d after lesion denervated dendrites of interneurons are subsequently lost. In contrast, the recruitment of microglia was impaired in CXCR3 knock-out mice, and, strikingly, denervated distal dendrites were maintained in zones of axonal degeneration. No differences between wild-type and knock-out mice were observed after facial nerve axotomy, as a lesion model for assessing microglial proliferation. This shows that CXCR3 signaling is crucial in microglia recruitment but not proliferation, and this recruitment is an essential element for neuronal reorganization.

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Microglial cells represent the major immunocompetent element of the CNS and are activated by any type of brain injury or disease. A candidate for signaling neuronal injury to microglial cells is the CC chemokine ligand CCL21, given that damaged neurons express CCL21. Investigating microglia in acute slices and in culture, we demonstrate that a local application of CCL21 for 30 s triggered a Cl− conductance with lasted for tens of minutes. This response was sensitive to the Cl− channel blockers 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid and 4-acetamide-4′-isothiocyanatostilbene, 2,2′-disulfonic acid. Moreover, CCL21 triggered a chemotaxis response, which was sensitive to Cl− channel blockers. In microglial cells cultured from CCR7 knockout mice, CCL21 produced the same type of Cl− current as well as a chemotaxis response. In contrast, in microglial cells from CXCR3 knockout mice, CCL21 triggered neither a Cl− conductance nor a chemotaxis response after CCL21 application. We conclude that the CCL21-induced Cl− current is a prerequisite for the chemotaxis response mediated by the activation of CXCR3 but not CCR7 receptors, indicating that in brain CCL21 acts via a different receptor system than in lymphoid organs.

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Statin treatment is proposed to be a new potential therapy for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. The effects of statin treatment on brain cells, however, are hardly understood. We therefore evaluated the effects of simvastatin treatment on the migratory capacity of brain microglial cells, key elements in the pathogenesis of MS. It is shown that exposure of human and murine microglial cells to simvastatin reduced cell surface expression of the chemokine receptors CCR5 and CXCR3. In addition, simvastatin treatment specifically abolished chemokine-induced microglial cell motility, altered actin cytoskeleton distribution, and led to changes in intracellular vesicles. These data clearly show that simvastatin inhibits several immunological properties of microglia, which may provide a rationale for statin treatment in MS.