Biomedical subjects

Silke Sachse

Publications and source records attributed to Silke Sachse.

7 recordsLinked to original sources

PubMed2006

Role of histamine as a putative inhibitory transmitter in the honeybee antennal lobe.

BACKGROUND: Odors are represented by specific spatio-temporal activity patterns in the olfactory bulb of vertebrates and its insect analogue, the antennal lobe. In honeybees inhibitory circuits in the AL are involved in the processing of odors to shape afferent odor responses. GABA is known as an inhibitory transmitter in the antennal lobe, but not all interneurons are GABAergic. Therefore we sought to analyze the functional role of the inhibitory transmitter histamine for the processing of odors in the honeybee AL. RESULTS: We optically recorded the representation of odors before, during and after histamine application at the input level (estimated from a compound signal), and at the output level (by selectively measuring the projection neurons). For both, histamine led to a strong and reversible reduction of odor-evoked responses. CONCLUSION: We propose that histamine, in addition to GABA, acts as an inhibitory transmitter in the honeybee AL and is therefore likely to play a role in odor processing.

Journal Article↗

PubMed2006

Atypical membrane topology and heteromeric function of Drosophila odorant receptors in vivo.

Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors (ORs): a divergent member of the OR family and the highly conserved, broadly expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances OR function in vitro, but the molecular mechanism by which it acts is unknown. Here we demonstrate that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is necessary and sufficient to promote functional reconstitution of odor-evoked signaling in sensory neurons that normally respond only to carbon dioxide. Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, we find that Drosophila ORs and OR83b adopt a novel membrane topology with their N-termini and the most conserved loops in the cytoplasm. These loops mediate direct association of ORs with OR83b. Our results reveal that OR83b is a universal and integral part of the functional OR in Drosophila. This atypical heteromeric and topological design appears to be an insect-specific solution for odor recognition, making the OR/OR83b complex an attractive target for the development of highly selective insect repellents to disrupt olfactory-mediated host-seeking behaviors of insect disease vectors.

Animals↗

PubMed2005

Computational modeling suggests that response properties rather than spatial position determine connectivity between olfactory glomeruli.

Olfactory responses require the representation of high-dimensional olfactory stimuli within the constraints of two-dimensional neural networks. We used a computational model of the honeybee antennal lobe to test how inhibitory interactions in the antennal lobe should be organized to best reproduce the experimentally measured input-output function in this structure. Our simulations show that a functionally organized inhibitory network, as opposed to an anatomically or all-to-all organized inhibitory network, best reproduces the input-output function of the antennal lobe observed with calcium imaging. In this network, inhibition between each pair of glomeruli was proportional to the similarity of their odor-response profiles. We conclude that contrast enhancement between odorants in the honeybee antennal lobe is best achieved when interglomerular inhibition is organized based on glomerular odor response profiles rather than on anatomical neighborhood relations.

Animals↗

PubMed2004

Odor-driven attractor dynamics in the antennal lobe allow for simple and rapid olfactory pattern classification.

The antennal lobe plays a central role for odor processing in insects, as demonstrated by electrophysiological and imaging experiments. Here we analyze the detailed temporal evolution of glomerular activity patterns in the antennal lobe of honeybees. We represent these spatiotemporal patterns as trajectories in a multidimensional space, where each dimension accounts for the activity of one glomerulus. Our data show that the trajectories reach odor-specific steady states (attractors) that correspond to stable activity patterns at about 1 second after stimulus onset. As revealed by a detailed mathematical investigation, the trajectories are characterized by different phases: response onset, steady-state plateau, response offset, and periods of spontaneous activity. An analysis based on support-vector machines quantifies the odor specificity of the attractors and the optimal time needed for odor discrimination. The results support the hypothesis of a spatial olfactory code in the antennal lobe and suggest a perceptron-like readout mechanism that is biologically implemented in a downstream network, such as the mushroom body.

Animals↗

PubMed2003

The coding of odour-intensity in the honeybee antennal lobe: local computation optimizes odour representation.

We investigated strategies involved in odour intensity coding by the primary olfactory centre of insects, the antennal lobe (AL), the structural and functional analogue of the olfactory bulb. Using calcium imaging in the honeybee, we simultaneously measured the projection neuron output responses and a compound signal dominated by receptor neuron input in identified olfactory glomeruli to odours spanning seven log units of concentration. A comparison of the two processing levels indicates that the intercellular computation within the AL modulates and contrast-enhances the primary olfactory signals. As a result the AL network optimizes the olfactory code: odour representation is improved at lower concentrations, the relative activity of olfactory glomeruli allows encoding odour quality over up to four log-unit concentrations, and odour-intensity is reliably represented in the overall excitation across AL.

Aldehydes↗

PubMed2002

Genetically expressed cameleon in Drosophila melanogaster is used to visualize olfactory information in projection neurons.

Complex external stimuli such as odorants are believed to be internally represented in the brain by spatiotemporal activity patterns of extensive neuronal ensembles. These activity patterns can be recorded by optical imaging techniques. However, optical imaging with conventional fluorescence dyes usually does not allow for resolving the activity of biologically defined groups of neurons. Therefore, specifically targeting reporter molecules to neuron populations of common genetic identity is an important goal. We report the use of the genetically encoded calcium-sensitive fluorescence protein cameleon 2.1 in the Drosophila brain. We visualized odorant-evoked intracellular calcium concentration changes in selectively labeled olfactory projection neurons both postsynaptically in the antennal lobe, the primary olfactory neuropil, and presynaptically in the mushroom body calyx, a structure involved in olfactory learning and memory. As a technical achievement, we show that calcium imaging with a genetically encoded fluorescence probe is feasible in a brain in vivo. This will allow one to combine Drosophila's advanced genetic tools with the physiological analysis of brain function. Moreover, we report for the first time optical imaging recordings in synaptic regions of the Drosophila mushroom body calyx and antennal lobe. This provides an important step for the use of Drosophila as a model system in olfaction.

Animals↗

PubMed2002

Role of inhibition for temporal and spatial odor representation in olfactory output neurons: a calcium imaging study.

The primary olfactory brain center, the antennal lobe (AL) in insects or the olfactory bulb in vertebrates, is a notable example of a neural network for sensory processing. While physiological properties of the input, the olfactory receptor neurons, have become clearer, the operation of the network itself remains cryptic. Therefore we measured spatio-temporal odor-response patterns in the output neurons of the olfactory glomeruli using optical imaging in the honeybee Apis mellifera. We mapped these responses to identified glomeruli, which are the structural and functional units of the AL. Each odor evoked a complex spatio-temporal activity pattern of excited and inhibited glomeruli. These properties were odor- and glomerulus-specific and were conserved across individuals. We compared the spatial pattern of excited glomeruli to previously published signals, which derived mainly from the receptor neurons, and found that they appeared more confined, showing that inhibitory connections enhance the contrast between glomeruli in the AL. To investigate the underlying mechanisms, we applied GABA and the GABA-receptor antagonist picrotoxin (PTX). The results show the presence of two separate inhibitory networks: one is GABAergic and modulates overall AL activity, the other is PTX-insensitive and glomerulus-specific. Inhibitory connections of the latter network selectively inhibit glomeruli with overlapping response profiles, in a way akin to "lateral" inhibition in other sensory systems. Selectively inhibited glomeruli need not be spatial neighbors. The net result is a globally modulated, contrast-enhanced and predictable representation of odors in the olfactory output neurons.

Animals↗