A Combined Clock and Compass

In animals with magnetoreception, there may be the possibility that cryptochrome (with its connection to both a navigation strategy, and circadian rhythms) may be supporting in an integrated sense of time and place through a system that combined together a clock and compass. Evidence of such a system has been indicated in various species and this is explored further in this posting.

The two genes Cry1 and Cry2 code for the two cryptochrome proteins CRY1 and CRY2. ….In Drosophila, cryptochrome (dCRY) acts as a blue-light photoreceptor that directly modulates light input into the circadian clock, while in mammals, cryptochromes (CRY1 and CRY2) act as transcription repressors within the circadian clockwork. Some insects, including the monarch butterfly, have both a mammal-like and a Drosophila-like version of cryptochrome, providing evidence for an ancestral clock mechanism involving both light-sensing and transcriptional-repression roles for cryptochrome. 

It has also been shown that mammalian-like Cry2 is necessary for a genuine directional response to periodic rotations of the Geomagnetic field vector in two insect species. Findings identified the eye-localized Cry2 as an indispensable component and a likely photoreceptor of the directional GMF response. O Bazalova et al 2015. Some species, who’s cones do not contain active cryptochrome 1, e.g some rodents and bats, are reactive to the magnetic field. C Nießner et al 2016.

The Cryptochrome protein (CRY) in Arabidopsis, Drosophila, and mouse provide the most direct path by which redox status can interact with the core components of the circadian transcription–translation feedback loop (TTFL), and is an example of the emerging coupling of redox with circadian rhythms. Perturbation of the transcription–translation feedback loop clockwork or the redox system results in a perturbation of the other, indicating that they have a reciprocal relationship. Lisa Wulund 2015,  A Stangherlin – ‎2013. K Nishio 2015. N B Milev 2015. This has major implications for neurology. M U. Gillette 2014.

The link between redox and circadian rhythms through cryptochrome (and possibly other mechanisms) could offer the basis for an integrated clock/compass mechanism in various species. Some possible examples are explored below.

Existing Evidence of Possible Combined Clock/Magnetoreception in Insects

Monarch butterflies use an internal circadian clock to calibrate the information they get from the position of the sun. It was always assumed that the circadian clock that modulates the navigation of the monarch was in the brain, since other circadian clocks are found there. It has, however, been found that monarchs need their antennae to properly calibrate their sun compass. C Merlin 2009. The Monarch butterfly also possesses an inclination magnetic compass to help direct their flight equatorward in the fall. PA Guerra – ‎2014 

Data suggests that the clock gene CRY2 may have a dual role in the monarch butterfly’s brain—as a core clock element and as an output that regulates circadian activity in the central complex, the likely site of the sun compass. Hugh Dingle 2014. H Zhu – ‎2008

A CRY1-staining neural pathway has been identified that may connect the circadian (navigational) clock to polarized light input important for sun compass navigation, and a CRY2-positive neural pathway has been discovered that may communicate circadian information directly from the circadian clock to the central complex Steven Reppert 2007. To navigate their migration route, the butterflies use a time-compensated compass….all four clock genes are expressed in both the antennal bulb and flagellum, and it would appear that light entrained circadian clocks are distributed throughout the length of the monarch butterfly antenna. PA Guerra – ‎2012.

The Drosophilas circadian clock is sensitive to the magnetic fields and this depends on the activation of cryptochrome and on the applied field strength. The flies exposed to the static magnetic fields enhanced slowing of clock rhythms and this effect was maximal at 300 μT. Chathurika D. Abeyrathne 2010.  T Yoshii – ‎2009. In Drosophila it has been proposed that CRY activation involves intramolecular electron transfer and presumably subsequent conformational changes; thus, the cellular redox status also regulates the transfer of photic information and CRY stability. Results suggest that cellular redox status and electron transfer modulate the light-dependent activation of CRY, which in turn affects the subsequent transmission of the light signal to TIM and the degradation of CRY itself, with the subsequent clock resetting. M L Fanjul-Moles 2015. 

In honey bees, the circadian clocks is also involved in time memory, and foragers staying for long periods in the hive, use the clock to correct their waggle dance in accordance to the sun’s azimuth. A Eban Rothschild 2012. On a honeycomb they are found to orient themselves with the eight cardinal directions. However, when the magnetic field is disrupted by being zeroed out or increased too much, then they lose their orientation sense.

Other possible examples where there may be a combination of clock and compass in insects

It has also been found that a reduced magnetic field may affect positive phototaxis and flight capacity of a migratory rice planthopper – potentially acting through an antioxidative stress-related CRYs-circadian clock-AKH/AKHR signalling pathwayGui-Jun Wan 2016.

In A. mellifera, general anesthesia for 6 h in daytime delayed the phase of the circadian rhythms in foraging time, locomotor activity in hives, and clock gene expression, and changed the orientation with an anticlockwise shift in the Southern Hemisphere and with a clockwise shift in the Northern Hemisphere in solar compass navigation.

Migration of the Pachycondyla marginata ant is significantly oriented at 13 degrees with respect to the geomagnetic north-south axis. On the basis of previous magnetic measurements of individual parts of the body (antennae, head, thorax and abdomen), the antennae were suggested to host a magnetoreceptor. J F de Oliveira JF 2010

Solar compass orientation of the desert locust, Schistocerca gregaria, requires time compensation for changes in solar elevation in addition to the azimuthal compensation…recent experimental results show that some of clock genes are also involved in photoperiodism.   H Numata – ‎2015

Evidence of a Possible Combined Clock/Magnetoreception in Crustacea.

Evidence indicates that the circadian rhythms of crayfish are controlled by a distributed circadian system that includes four pairs of coupled oscillators, and two extraretinal circadian photoreceptors sensitive to blue light, which are involved in photic entrainment. In the crayfish studies have demonstrated that these oscillators express clock proteins similar to those found in the Drosophila. In addition, the brain and the sixth abdominal ganglion extraretinal receptors express CRY. It has been proposed that the blue light-induced photo-entrainment of some rhythms in crayfish, particularly ERG amplitude and activity rhythms, are mediated by CRY. The changes produced by light intensity and photoperiod length in ROS and the antioxidant rhythms of crayfish inhabiting different latitudes suggest that a photo-oxidative redox signal may be contributing to this animal’s entrainment to latitudinal photoperiodic changes using similar signaling pathways as aquatic vertebrates to activate CCG transcription.  M L Fanjul-Moles 2015. 

Talitrid amphipods (the sandhoppers) represent a good biological model in the fields of animal orientation and biological rhythms. The two chronometric mechanisms of compensation for the apparent motion of the sun and moon (used by sandhoppers in zonal recovery based on two astronomical cues) seem to be independent of each other and to operate throughout the 24-hour period. The speed of the chronometric mechanism of solar compensation appears to be related to the hours of light and is entrained by the same stimulus (light-dark alternation) that controls the circadian activity rhythm. Therefore, it is probable that in T. saltator the same mechanism regulates both the circadian locomotor activity and the solar compensation. A Ugolini – ‎2003.

The only documented cases of magnetic orientation in Crustacea involve the beach orientation movements of sandhoppers. Joseph L. Kirschvink 2013. R Campan in “the Orientation and Communication of Arthropods” (edited by M Lehrer 1997) provides further examples including that of the sandhopper which uses a number of orientation mechanisms including phototaxis, geotaxis, scototaxis, polarotaxis, astrotaxis, and magnetotaxis (Pardi & Scapini 1987). The sandhoppers also possess the capacity to use local cues such as landmarks, wave activity, substrate channels, slopes, humidity and sand grain (Scapini et al 1992). They use these cues hierarchically, according to the local ecological conditions. On a sloped beach, geotaxis predominates, similar to a slope compass, whereas on stationary conspicuous dunes, scototaxis dominates. Orientation based on a solar, polarised or moon compass is general used on flat beaches where terrestrial cues are rare. In equatorial areas, sun compasses are used only a dusk and dawn, where the apparent sun azimuth provides reliable cues, whereas the magnetic compass dominates during the rest of the day (Pardi et al 1988). R Campan (1997) provides a number of further examples of magnetoreception in arthropods, including where this is combined with other orientation mechanisms.

Evidence of Redox – Circadian Coupling in Fish

In zebrafish cells, the light-induced redox changes stimulating intracellular mitogen- activated protein kinase (MAPK) signaling that transduces photic signals to zCry1a gene transactivation. Importantly, light also drives the production of intracellular ROS, such as H2O2 , that leads to an altered redox status and increases intracellular catalase activity by stimulating catalase transcription, an event which occurs after the maximum expression of the zCry1a gene has been reached. This increased catalase activity diminishes light nduced cellular ROS levels, resulting in decreased zCry1a transcription and creating a negative feedback loop. Thus, this altered redox state triggers the transduction of photic signals that regulate and synchronize the circadian clock. M L Fanjul-Moles 2015. 

Existing Evidence of a Possible Combined Clock/Magnetoreception in Birds

Much of the research on magnetoreception in birds have focused on European Robins and Homing Pigeons, Silvereyes and  Garden Warblers. There may be other examples.

Experiments on free flying Catharus thrushes suggest that in free flight, the magnetic compass is calibrated daily by sunset cues during twilight. Cochran et al 2004.

Hoffmann (1960) showed that starlings maintained in constant dim light exhibited gradual shifting in the bird’s orientation with a period equivalent to the period of their free running rhythms in locomotion. This data suggested that the orientation clock and the circadian clock shared clock properties. VM Cassone – ‎2014

Savannah and White-throated sparrows calibrate their magnetic compass by polarized light cues during both autumn and spring migration. Sunrise exposure to an artificial polarization pattern shifted relative to the natural magnetic field or exposure to a shift of the magnetic field relative to the natural sky both led to recalibration of the magnetic compass. Muheim R, Phillips 2009 

Existing Evidence of a Possible Combined Clock/Magnetoreception in Reptiles

Sun compass orientation has been proposed as a mechanism that may also contribute to migrating processes, and it has been studied in orientation and navigation in terrestrial turtles (DeRosa & Taylor 1978; Southwood & Avens 2011), but few studies have investigated these mechanisms in marine species (Alerstam 2006). Sea turtles are magnetoreceptive, and work has been carried out on sun compass orientation (Kristel L. Gopar-Canales 2013), but not on a possible combined clock/magnetoreceptive mechanism.

Existing Evidence of a Possible Combined Clock/Magnetoreception in Mammals

It has been found that an ELF-MF (0.1 mT, 50 Hz) exposure is capable of entraining expression of clock genes BMAL1, PER2, PER3, CRY1, and CRY2. Moreover, ELF-MF treatment induced an alteration in circadian clock gene expression previously entrained by serum shock stimulation. These results support the hypothesis that ELF-MF may be able to drive circadian physiologic processes by modulating peripheral clock gene expression. N Manzella 2015

Yellon and Wilson et al, documenting the effects of magnetic fields, were the first to report a reduction of both in pineal and plasma melatonin in Djungarian hamsters with a short exposure to a sinusoidal 100-μT magnetic field. In addition, Wilson et al also reported an increase in the concentration of norepinephrine in the suprachiasmatic nuclei, the central rhythm-generating system. Kato et al,in exposing male Wistar-King rats for 6 weeks to a 50-Hz circularly polarized sinusoidal magnetic field using increasing intensities, showed a decrease in pineal and plasma melatonin concentrations without any dose-response relationship. Kato et al then documented in Long-Evans rats the same intensities of a circularly polarized magnetic field and showed a reduction of pineal and plasma melatonin concentrations. Other studies on rats or mice, baboons, and hamsters also showed a reduction in the nighttime peak of melatonin. However evidence of magnetic effects on melatonin levels in other animals has been patchy and inconclusive.  Yvan Touitou 2012.

The magnetic fields of 50 Hz have influenced the biological clock activity when the field was directed in the horizontal plane of the rat brain. Exposure to a 50-hz magnetic field induces a circadian rhythm in 6-hydroxymelatonin sulfate excretion in mice.  Kumlin T 2005.

It has also been pointed out that magnetoreception is likely to be connected to other navigational systems e.g

In the Ansell’s mole rat (a mammal) It has been shown that magnetic information is integrated with multimodal sensory and motor information into a common spatial representation of allocentric space within the superior colliculus, the head direction system and the entorhinal–hippocampal spatial representation system (Nemec et al.,2001; Burger et al., 2010). “The specific mechanisms underlying this integration have yet to be identified and characterized. Ludmila Oliveriusová et al 2012

Links to Human Neurology

J Kirschvink (Caltech) claims to have found evidence of magnetoreception in human beings (June 2016). He has used a Faraday cage to demonstrate that human brains can be influenced by magnetic fields. When the magnetic field is rotating counterclockwise, there’s a drop in participants’ alpha waves. The suppression of α waves, in the EEG world, is associated with brain processing: a set of neurons were firing in response to the magnetic field, the only changing variable. Currently the sample size is very small (24 participants) and the results need to be peer reviewed for publishing, but it will be interesting to see further information on this in the future. The mechanism behind such magnetoreception is unknown.

Cryptochrome is found throughout adult human retina. CRY2 is localized throughout the cytoplasm of cells in the ganglion cell layer as well as within nuclei… C L Thompson et al 2003. Human cryptochrome 2 protein (hCRY2), can sense magnetic fields when implanted into Drosophila. LE Foley – ‎2011. In mammals the 2 forms of cryptochrome are located in the retina, absorb blue light and transfer the light signal to the SCN. Two proteins alternatively build up and turn on and off each others genes for production, thus forming an accurate internal clock for each of the tens of thousands of cells in the SCN.  D Ono 2013.

Brain tissue itself has magnetic properties (similar to a protein metallic nanoparticle) and open hysteresis loops have been observed on human brain tissue at room temperature (A Hirt and F Bream 2006). Recently it has been found that neurons can be stimulated with (iron oxide) nanoparticles, allowing them to activate brain cells remotely using light or magnetic fields. (R Chen et al 2015).

In transgenic C Elegans, expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4-specific neurons, application of an external magnetic field triggered muscle contraction and withdrawal behaviour of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons. It was also found that the magnetoreceptor could evoke membrane depolrisation and action potentials, generate calcium influx, and trigger neuronal activity in both HEK-293 cells and cultured primary hippocampal neurons when activated by a remote magnetic field. The magnetogenetic control of neuronal activity could be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for external magnetic fields applied. The group also screened other species’ genomes and showed variants of both proteins were highly conserved across several animals, including pigeons, monarch butterflies, whales and even humans. X Long 2016

There is a large amount of research findings on the impact of TMS on neural activity, function and behaviour. If it is found that humans are magnetoreceptive in any way, this could help us understand how such a navigation function influences the wider organism. Links between TMS and magnetoreception have already been made by scientists e.g A V Chervyakov 2015 who suggests that quantum effects underlie the therapeutic benefits of TMS in relation to a number of pathological conditions, including neurological and CNS conditions. Chervyakov notes that another important aspect of TMS action is its impact on neuroprotective mechanisms. It has been found that the effects of magnetic stimulation influence a variety of factors including neuronal morphology, glial cells, neurogenesis, cell differentiation and proliferation, apoptotic mechanisms, the concentration of neuromediators, ATP, and neurotrophic factors including glucose metabolism, and the expression of certain genes.

Endogenous expression of tailored nanoparticles in cells followed by application of low-frequency radio waves or a magnetic field can be used to noninvasively modulate gene expression. I B Leibiger 2015. This study found that radiogenetics and magnetogenetics can be used to regulate glucose homeostatis. This in turn may be linked to biological clocks, as it has been found that cryptochrome regulates glucose production in the liver, and that a smaller molecule KL001 can stabilise the cryptochrome, by preventing it being sent to the proteasomes.  EE Zhang – ‎2010S Kay 2012. 

 

March 2016. This article merely joins up other peoples work into an overall system.  These works have been referenced so it is clear that others have provided the individual pieces of evidence that have been used to shape a specific systems approach.     

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