Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation

Abstract

Migratory birds can use a magnetic compass for orientation during their migratory journeys covering thousands of kilometers. But how do they sense the reference direction provided by the Earth's magnetic field? Behavioral evidence and theoretical considerations have suggested that radical-pair processes in differently oriented, light-sensitive molecules of the retina could enable migratory birds to perceive the magnetic field as visual patterns. The cryptochromes (CRYs) have been suggested as the most likely candidate class of molecules, but do CRYs exist in the retina of migratory birds? Here, we show that at least one CRY1 and one CRY2 exist in the retina of migratory garden warblers and that garden-warbler CRY1 (gwCRY1) is cytosolic. We also show that gwCRY1 is concentrated in specific cells, particularly in ganglion cells and in large displaced ganglion cells, which also showed high levels of neuronal activity at night, when our garden warblers performed magnetic orientation. In addition, there seem to be striking differences in CRY1 expression between migratory and nonmigratory songbirds at night. The difference in CRY1 expression between migrants and nonmigrants is particularly pronounced in the large displaced ganglion cells known to project exclusively to a brain area where magnetically sensitive neurons have been reported. Consequently, cytosolic gwCRY1 is well placed to possibly be the primary magnetic-sensory molecule required for light-mediated magnetoreception.

Structure and Function of Animal Cryptochromes

“…Light and eyes are required for certain migratory behaviors, and CRY has been found in photoreceptor tissues of several organisms. In the migratory bird garden warbler (Sylvia borin), CRY expression was localized in a subset of retinal ganglion cells associated with magnetic orientation behavior (Mouritsen et al 2004). Other theories and potential magnetoreceptors exist; however, this is clearly a fertile field of research that will possibly include characterization of exciting new CRY functions as it develops.…”

Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes

“…In vertebrates having both (6-4) PHR and clock CRY proteins, (6-4) PHR does not disturb the circadian clock, and conversely clockwork CRYs do not appear to directly contribute to DNA repair (22,23). Clockwork CRYs from different species have also been implicated in diverse processes, including nonvisual photoreception, sun compass orientation, and time-place learning (24)(25)(26)(27)(28)(29)(30)(31)). Yet, delays in mechanistic characterization of clock CRYs, caused in part by technical difficulties in protein expression and thus structure determination, have hampered biological understanding.…”

Magnetic field changes activate the trigeminal brainstem complex in a migratory bird

“…Consequently, we used a nonelectronic technique: behavioral molecular mapping based on quantification of the neuronal activity-dependent marker ZENK (19,20,(25)(26)(27)(28). The major advantages of a behavioral molecular mapping approach compared with an electrophysiological approach are that we could obtain, in a noninvasive manner, a record of neuronal activation in the brain from awake, unrestrained birds, and that the potential artifacts often associated with the combination of electrophysiology and magnetic field stimuli could be avoided.…”

“…In recent years, mounting behavioral and anatomical evidence has been accumulating that birds, at least, might have two independent magnetic senses: (i) iron-mineral-based sensors located in the upper beak, which are innervated by the ophthalmic branch of the trigeminal nerve (V1) (8,9,(11)(12)(13)(14)(15)(16), and (ii) a light-dependent chemical sense which is embedded in parts of the visual system (7,9,(16)(17)(18)(19)(20)(21). However, considerable scientific skepticism remains regarding both of these proposed magnetic senses because, so far, in birds, the studies that have reported changes in neurophysiological activity in response to magnetic field changes differ in their conclusions, could not be independently confirmed, and are likely to have been subject to artifactual difficulties (22)(23)(24).…”