Neuroarchitecture of the central complex in the Madeira cockroach Rhyparobia maderae: Pontine and columnar neuronal cell types.

Insects have evolved remarkable abilities to navigate over short distances and during long-range seasonal migrations. The central complex (CX) is a navigation center in the insect brain that controls spatial orientation and directed locomotion. It is composed of the protocerebral bridge (PB), the upper (CBU) and lower (CBL) division of the central body, and a pair of noduli. While most of its functional organization and involvement in head-direction coding has been obtained from work on flies, bees, and locusts that largely rely on vision for navigation, little contribution has been provided by work on nocturnal species. To close this gap, we have investigated the columnar organization of the CX in the cockroach Rhyparobia maderae. Rhyparobia maderae is a highly agile nocturnal insect that relies largely but not exclusively on antennal information for navigation. A particular feature of the cockroach CX is an organization of the CBU and CBL into interleaved series of eight and nine columns. Single-cell tracer injections combined with imaging and 3D analysis revealed five systems of pontine neurons connecting columns along the vertical and horizontal axis and 18 systems of columnar neurons with topographically organized projection patterns. Among these are six types of neurons with no correspondence in other species. Many neurons send processes into the anterior lip, a brain area highly reduced in bees and unknown in flies. While sharing many features with the CX in other species, the cockroach CX shows some unique attributes that may be related to the ecological niche of this insect.

The sky compass network in the brain of the desert locust.

Many arthropods and vertebrates use celestial signals such as the position of the sun during the day or stars at night as compass cues for spatial orientation. The neural network underlying sky compass coding in the brain has been studied in great detail in the desert locust Schistocerca gregaria. These insects perform long-range migrations in Northern Africa and the Middle East following seasonal changes in rainfall. Highly specialized photoreceptors in a dorsal rim area of their compound eyes are sensitive to the polarization of the sky, generated by scattered sunlight. These signals are combined with direct information on the sun position in the optic lobe and anterior optic tubercle and converge from both eyes in a midline crossing brain structure, the central complex. Here, head direction coding is achieved by a compass-like arrangement of columns signaling solar azimuth through a 360° range of space by combining direct brightness cues from the sun with polarization cues matching the polarization pattern of the sky. Other directional cues derived from wind direction and internal self-rotation input are likely integrated. Signals are transmitted as coherent steering commands to descending neurons for directional control of locomotion and flight.

3D-atlas of the brain of the cockroach Rhyparobia maderae.

The Madeira cockroach Rhyparobia maderae is a nocturnal insect and a prominent model organism for the study of circadian rhythms. Its master circadian clock, controlling circadian locomotor activity and sleep-wake cycles, is located in the accessory medulla of the optic lobe. For a better understanding of brain regions controlled by the circadian clock and brain organization of this insect in general, we created a three-dimensional (3D) reconstruction of all neuropils of the cerebral ganglia based on anti-synapsin and anti-γ-aminobutyric acid immunolabeling of whole mount brains. Forty-nine major neuropils were identified and three-dimensionally reconstructed. Single-cell dye fills complement the data and provide evidence for distinct subdivisions of certain brain areas. Most neuropils defined in the fruit fly Drosophila melanogaster could be distinguished in the cockroach as well. However, some neuropils identified in the fruit fly do not exist as distinct entities in the cockroach while others are lacking in the fruit fly. In addition to neuropils, major fiber systems, tracts, and commissures were reconstructed and served as important landmarks separating brain areas. Being a nocturnal insect, R. maderae is an important new species to the growing collection of 3D insect brain atlases and only the second hemimetabolous insect, for which a detailed 3D brain atlas is available. This atlas will be highly valuable for an evolutionary comparison of insect brain organization and will greatly facilitate addressing brain areas that are supervised by the circadian clock.

Myoinhibitory peptides in the central complex of the locust Schistocerca gregaria and colocalization with locustatachykinin-related peptides.

The central complex in the brain of insects provides a neural network for sensorimotor processing that is essential for spatial navigation and locomotion and plays a role in sleep control. Studies on the neurochemical architecture of the central complex have been performed especially in the fruit fly Drosophila melangoaster and the desert locust, Schistocerca gregaria. In several insect species, myoinhibitory peptides (MIPs) are involved in circadian control and sleep-wake regulation. To identify neurons that might underlie these functions, we investigated the distribution of MIPs in the central complex of the locust. In silico transcript analysis suggests the presence of eight different MIPs in the desert locust. Through immunolabeling, we identified five systems of central-complex neurons that express MIP-like peptides. Two systems constitute columnar neurons of the protocerebral bridge and the lower division of the central body, while the other three systems are columnar neurons (two systems) and tangential neurons (one system) of the upper division of the central body. The innervation pattern and cell count of two systems of columnar neurons revealed the existence of 18 instead of 16 columns of the protocerebral bridge. Immunostaining of preparations containing intracellularly stained single cells allowed us to further specify subtypes of labeled columnar neurons. Double-label experiments showed that three systems of MIP-immunostained columnar neurons are also locustatachykinin-immunoreactive. No colocalization was found with serotonin immunostaining. The data provide novel insights into the architecture of the locust central complex and suggest that MIPs play a prominent role within the central-complex network.

Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates.

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD pathology. Our interest in the life cycle of HTT led us to consider the development of high-affinity small-molecule binders of HTT oligomerized/amyloid-containing species that could serve as either cellular and in vivo imaging tools or potential therapeutic agents. We recently reported the development of PET tracers CHDI-180 and CHDI-626 as suitable for imaging mHTT aggregates, and here we present an in-depth pharmacological investigation of their binding characteristics. We have implemented an array of in vitro and ex vivo radiometric binding assays using recombinant HTT, brain homogenate-derived HTT aggregates, and brain sections from mouse HD models and humans post-mortem to investigate binding affinities and selectivity against other pathological proteins from indications such as Alzheimer's disease and spinocerebellar ataxia 1. Radioligand binding assays and autoradiography studies using brain homogenates and tissue sections from HD mouse models showed that CHDI-180 and CHDI-626 specifically bind mHTT aggregates that accumulate with age and disease progression. Finally, we characterized CHDI-180 and CHDI-626 regarding their off-target selectivity and binding affinity to beta amyloid plaques in brain sections and homogenates from Alzheimer's disease patients.

Organization and neural connections of the lateral complex in the brain of the desert locust.

The lateral complexes (LXs) are bilaterally paired neuropils in the insect brain that mediate communication between the central complex (CX), a brain center controlling spatial orientation, various sensory processing areas, and thoracic motor centers that execute locomotion. The LX of the desert locust consists of the lateral accessory lobe (LAL), and the medial and lateral bulb. We have analyzed the anatomical organization and the neuronal connections of the LX in the locust, to provide a basis for future functional studies. Reanalyzing the morphology of neurons connecting the CX and the LX revealed likely feedback loops in the sky compass network of the CX via connections in the gall of the LAL and a newly identified neuropil termed ovoid body. In addition, we characterized 16 different types of neuron that connect the LAL with other areas in the brain. Eight types of neuron provide information flow between both LALs, five types are LAL input neurons, and three types are LAL output neurons. Among these are neurons providing input from sensory brain areas such as the lobula and antennal neuropils. Brain regions most often targeted by LAL neurons are the posterior slope, the wedge, and the crepine. Two descending neurons with dendrites in the LAL were identified. Our data support and complement existing knowledge about how the LAL is embedded in the neuronal network involved in processing of sensory information and generation of appropriate behavioral output for goal-directed locomotion.

[The flu epidemic after World War I and homeopathy--an international comparison]. / Die Grippe-Pandemie nach dem Ersten Weltkrieg und die Homöopathie im internationalen Vergleich.

The "Spanish Flu" began in 1918 and was the most devastating pandemic in human history that had ever been, claiming more lives than World War I. The flu virus had not yet been discovered, and the usual therapy measures were merely symptomatic. In many parts of the world the pandemic was treated by homeopaths. At the time, homeopathic medical practices, out-patient clinics and hospitals existed in various countries. To this day homeopaths refer to the successful homeopathic treatment of the "Spanish Flu". The following paper looks at what this treatment consisted in and whether it was based on a particular concept. It also examines contemporary evaluations and figures, as well as the question as to whether homeopathy experienced a rise in demand as a consequence of its success during the pandemic.