Upper bound for broadband radiofrequency field disruption of magnetic compass orientation in night-migratory songbirds.

Night-migratory songbirds have a light-dependent magnetic compass sense, the mechanism of which is thought to depend on the photochemical formation of radical pairs in cryptochrome (Cry) proteins located in the retina. The finding that weak radiofrequency (RF) electromagnetic fields can prevent birds from orienting in the Earth's magnetic field has been regarded as a diagnostic test for this mechanism and as a potential source of information on the identities of the radicals. The maximum frequency that could cause such disorientation has been predicted to lie between 120 and 220 MHz for a flavin-tryptophan radical pair in Cry. Here we show that the magnetic orientation capabilities of Eurasian blackcaps (Sylvia atricapilla) are not affected by RF noise in the frequency bands 140 to 150 MHz and 235 to 245 MHz. From a consideration of its internal magnetic interactions, we argue that RF field effects on a flavin-containing radical-pair sensor should be approximately independent of frequency up to 116 MHz and that birds' sensitivity to RF disorientation should fall by about two orders of magnitude when the frequency exceeds 116 MHz. Taken together with our earlier finding that 75 to 85 MHz RF fields disrupt the magnetic orientation of blackcaps, these results provide compelling evidence that the magnetic compass of migratory birds operates by a radical pair mechanism.

Broadband 75-85 MHz radiofrequency fields disrupt magnetic compass orientation in night-migratory songbirds consistent with a flavin-based radical pair magnetoreceptor.

The light-dependent magnetic compass sense of night-migratory songbirds can be disrupted by weak radiofrequency fields. This finding supports a quantum mechanical, radical-pair-based mechanism of magnetoreception as observed for isolated cryptochrome 4, a protein found in birds' retinas. The exact identity of the magnetically sensitive radicals in cryptochrome is uncertain in vivo, but their formation seems to require a bound flavin adenine dinucleotide chromophore and a chain of four tryptophan residues within the protein. Resulting from the hyperfine interactions of nuclear spins with the unpaired electrons, the sensitivity of the radicals to radiofrequency magnetic fields depends strongly on the number of magnetic nuclei (hydrogen and nitrogen atoms) they contain. Quantum-chemical calculations suggested that electromagnetic noise in the frequency range 75-85 MHz could give information about the identity of the radicals involved. Here, we show that broadband 75-85 MHz radiofrequency fields prevent a night-migratory songbird from using its magnetic compass in behavioural experiments. These results indicate that at least one of the components of the radical pair involved in the sensory process of avian magnetoreception must contain a substantial number of strong hyperfine interactions as would be the case if a flavin-tryptophan radical pair were the magnetic sensor.

Prussian blue technique is prone to yield false negative results in magnetoreception research.

Perls's Prussian blue staining technique has been used in magnetoreception research to screen tissues for iron-rich structures as proxies for putative magnetoreceptor structures based on magnetic particles. However, seemingly promising structural candidates in the upper beak of birds detected with Prussian blue turned out to be either irreproducible or located in non-neuronal cells, which has spurred a controversy that has not been settled yet. Here we identify possible pitfalls in the previous works and apply the Prussian blue technique to tissues implicated in magnetic-particle-based magnetoreception, in an effort to reassess its suitability for staining single-domain magnetite, i.e., the proposed magnetic substrate for the interaction with the external magnetic field. In the upper beak of night-migratory songbirds, we found staining products in great numbers, but not remotely associated with fiber terminals of the traced ophthalmic branch of the trigeminal nerve. Surprisingly, staining products were absent from the lamina propria in the olfactory rosette of rainbow trout where candidate magnetoreceptor structures were identified with different techniques earlier. Critically, magnetosome chains in whole cells of magnetotactic bacteria remained unstained. The failure to label single-domain magnetite in positive control samples is a serious limitation of the technique and suggests that two most influential but antipodal studies conducted previously stood little chances of obtaining correct positive results under the assumption that magnetosome-like particles were present in the tissues. Nonetheless, the staining technique appears suitable to identify tissue contamination with iron-rich fine dust trapped in epithelia already in vivo.

In Search for the Avian Trigeminal Magnetic Sensor: Distribution of Peripheral and Central Terminals of Ophthalmic Sensory Neurons in the Night-Migratory Eurasian Blackcap (Sylvia atricapilla).

In night-migratory songbirds, neurobiological and behavioral evidence suggest the existence of a magnetic sense associated with the ophthalmic branch of the trigeminal nerve (V1), possibly providing magnetic positional information. Curiously, neither the unequivocal existence, structural nature, nor the exact location of any sensory structure has been revealed to date. Here, we used neuronal tract tracing to map both the innervation fields in the upper beak and the detailed trigeminal brainstem terminations of the medial and lateral V1 subbranches in the night-migratory Eurasian Blackcap (Sylvia atricapilla). The medial V1 subbranch takes its course along the ventral part of the upper beak to innervate subepidermal layers and the mucosa of the nasal cavity, whereas the lateral V1 subbranch runs along dorsolateral levels until the nostrils to innervate mainly the skin of the upper beak. In the trigeminal brainstem, medial V1 terminals innervate both the dorsal part and the ventral, magnetically activated part of the principal sensory trigeminal brainstem nuclei (PrV). In contrast, the lateral V1 subbranch innervates only a small part of the ventral PrV. The spinal sensory trigeminal brainstem nuclei (SpV) receive topographically ordered projections. The medial V1 subbranch mainly innervates rostral and medial parts of SpV, whereas the lateral V1 subbranch mainly innervates the lateral and caudal parts of SpV. The present findings could provide valuable information for further analysis of the trigeminal magnetic sense of birds.

Morphology, biochemistry and connectivity of Cluster N and the hippocampal formation in a migratory bird.

The exceptional navigational capabilities of migrating birds are based on the perception and integration of a variety of natural orientation cues. The "Wulst" in the forebrain of night-migratory songbirds contains a brain area named "Cluster N", which is involved in processing directional navigational information derived from the Earth´s magnetic field. Cluster N is medially joined by the hippocampal formation, known to retrieve and utilise navigational information. To investigate the connectivity and neurochemical characteristics of Cluster N and the hippocampal formation of migratory birds, we performed morphological and histochemical analyses based on the expression of calbindin, calretinin, parvalbumin, glutamate receptor type 1 and early growth response protein-1 in the night-migratory Garden warbler (Sylvia borin) and mapped their mutual connections using neuronal tract tracing. The resulting expression patterns revealed regionally restricted neurochemical features, which mapped well onto the hippocampal and hyperpallial substructures known from other avian species. Magnetic field-induced neuronal activation covered caudal parts of the hyperpallium and the medially adjacent hippocampal dorsomedial/dorsolateral subdivisions. Neuronal tract tracings revealed connections between Cluster N and the hippocampal formation with the vast majority originating from the densocellular hyperpallium, either directly or indirectly via the area corticoidea dorsolateralis. Our data indicate that the densocellular hyperpallium could represent a central relay for the transmission of magnetic compass information to the hippocampal formation where it might be integrated with other navigational cues in night-migratory songbirds.

Morphology of the "prefrontal" nidopallium caudolaterale in the long-distance night-migratory Eurasian blackcap (Sylvia atricapilla).

Migrating birds have developed remarkable navigational capabilities to successfully master biannual journeys between their breeding and wintering grounds. To reach their intended destination, they need to calculate navigational goals from a large variety of natural directional and positional cues to set a meaningful motor output command. One brain area, which has been associated with such executive functions, is the nidopallium caudolaterale (NCL), which, due to its striking similarities in terms of neurochemistry, connectivity and function, is considered analogous to the mammalian prefrontal cortex. To establish a baseline for further analyses elucidating the neuronal correlates underlying avian navigation, we performed quantitative and qualitative analyses of dopaminergic fibres in the brains of long-distance night-migratory Eurasian blackcaps (Sylvia atricapilla). We identified four regions in the caudal telencephalon, each of which was characterized by its specific dopaminergic innervation pattern. At least three of them presumably constitute subareas of the NCL in Eurasian blackcaps and could thus be involved in integrating navigational input from different sensory systems. The observed heterogeneity and parcellation of the NCL subcompartments in this migratory species could be a consequence of the special demands related to navigation.

Prediction of necessity for coronary artery revascularization by adenosine contrast-enhanced magnetic resonance imaging.

BACKGROUND: Assessing myocardial first-pass wash-in during pharmacological induced stress allows detection of perfusion deficits and indicates stenotic coronary arteries (CA). The aim of our study was to demonstrate clinical relevance of contrast-enhanced stress magnetic resonance imaging (CMR) by predicting necessity of CA intervention. METHODS: 738 patients with scheduled coronary angiography (CXA) were scanned in a 1.5 Tesla CMR scanner. After 3 min of adenosine infusion (140 microg/kg/min), first-pass kinetic of contrast agent was evaluated. Myocardial necrosis was visualized with "myocardial late enhancement (MLE)". Perfusion deficits were described as either "ischemia in viable myocardium", or "no relevant ischemia in viable myocardium" or as "ischemia in chronic myocardial infarction (CMI)" based on spatial and temporal extent of ischemia and of MLE. CXA was performed in all patients within 48 h after CMR and revascularization, if applicable, was performed. Angiograms were read by two independent and blinded investigators and matched with CMR findings. RESULTS: 539 patients (73%) showed "ischemia in viable myocardium" and revascularization was performed in 513 patients (95%). In 111 patients with "no relevant ischemia in viable myocardium", revascularization was performed in only 5 patients (5%). In 88 patients classified as "ischemia in CMI", revascularization was performed in 14 patients (16%). Positive predictive value of CMR for CA intervention was 0.95, negative predictive value was 0.89, sensitivity was 0.96, and specificity was 0.87. CONCLUSION: CMR allows clinical useful prediction of relevant CA disease with need for revascularization prior to CXA and may be used as non-invasive test for myocardial ischemia and viability to guide further therapy.