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• W2985445317 abstract "•Magnetic stimuli activate neurons in the caudal vestibular nuclei•Magnetic stimuli induce a voltage in a model of a semicircular canal•Electroreceptive molecules are expressed in vestibular hair cells•We postulate that pigeons detect magnetic fields by electromagnetic induction A diverse array of vertebrate species employs the Earth’s magnetic field to assist navigation. Despite compelling behavioral evidence that a magnetic sense exists, the location of the primary sensory cells and the underlying molecular mechanisms remain unknown [1Johnsen S. Lohmann K.J. The physics and neurobiology of magnetoreception.Nat. Rev. Neurosci. 2005; 6: 703-712Crossref PubMed Scopus (309) Google Scholar]. To date, most research has focused on a light-dependent radical-pair-based concept and a system that is proposed to rely on biogenic magnetite (Fe3O4) [2Ritz T. Adem S. Schulten K. A model for photoreceptor-based magnetoreception in birds.Biophys. J. 2000; 78: 707-718Abstract Full Text Full Text PDF PubMed Scopus (827) Google Scholar, 3Kirschvink J.L. Walker M.M. Diebel C.E. Magnetite-based magnetoreception.Curr. Opin. Neurobiol. 2001; 11: 462-467Crossref PubMed Scopus (314) Google Scholar]. Here, we explore an overlooked hypothesis that predicts that animals detect magnetic fields by electromagnetic induction within the semicircular canals of the inner ear [4Viguier C. Le sens de l’orientation et ses organes chez les animaux et chez l’homme.Rev. Philos. France Let. 1882; : 1-36Google Scholar]. Employing an assay that relies on the neuronal activity marker C-FOS, we confirm that magnetic exposure results in activation of the caudal vestibular nuclei in pigeons that is independent of light [5Wu L.Q. Dickman J.D. Magnetoreception in an avian brain in part mediated by inner ear lagena.Curr. Biol. 2011; 21: 418-423Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. We show experimentally and by physical calculations that magnetic stimulation can induce electric fields in the pigeon semicircular canals that are within the physiological range of known electroreceptive systems. Drawing on this finding, we report the presence of a splice isoform of a voltage-gated calcium channel (CaV1.3) in the pigeon inner ear that has been shown to mediate electroreception in skates and sharks [6Bellono N.W. Leitch D.B. Julius D. Molecular tuning of electroreception in sharks and skates.Nature. 2018; 558: 122-126Crossref PubMed Scopus (18) Google Scholar]. We propose that pigeons detect magnetic fields by electromagnetic induction within the semicircular canals that is dependent on the presence of apically located voltage-gated cation channels in a population of electrosensory hair cells. A diverse array of vertebrate species employs the Earth’s magnetic field to assist navigation. Despite compelling behavioral evidence that a magnetic sense exists, the location of the primary sensory cells and the underlying molecular mechanisms remain unknown [1Johnsen S. Lohmann K.J. The physics and neurobiology of magnetoreception.Nat. Rev. Neurosci. 2005; 6: 703-712Crossref PubMed Scopus (309) Google Scholar]. To date, most research has focused on a light-dependent radical-pair-based concept and a system that is proposed to rely on biogenic magnetite (Fe3O4) [2Ritz T. Adem S. Schulten K. A model for photoreceptor-based magnetoreception in birds.Biophys. J. 2000; 78: 707-718Abstract Full Text Full Text PDF PubMed Scopus (827) Google Scholar, 3Kirschvink J.L. Walker M.M. Diebel C.E. Magnetite-based magnetoreception.Curr. Opin. Neurobiol. 2001; 11: 462-467Crossref PubMed Scopus (314) Google Scholar]. Here, we explore an overlooked hypothesis that predicts that animals detect magnetic fields by electromagnetic induction within the semicircular canals of the inner ear [4Viguier C. Le sens de l’orientation et ses organes chez les animaux et chez l’homme.Rev. Philos. France Let. 1882; : 1-36Google Scholar]. Employing an assay that relies on the neuronal activity marker C-FOS, we confirm that magnetic exposure results in activation of the caudal vestibular nuclei in pigeons that is independent of light [5Wu L.Q. Dickman J.D. Magnetoreception in an avian brain in part mediated by inner ear lagena.Curr. Biol. 2011; 21: 418-423Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. We show experimentally and by physical calculations that magnetic stimulation can induce electric fields in the pigeon semicircular canals that are within the physiological range of known electroreceptive systems. Drawing on this finding, we report the presence of a splice isoform of a voltage-gated calcium channel (CaV1.3) in the pigeon inner ear that has been shown to mediate electroreception in skates and sharks [6Bellono N.W. Leitch D.B. Julius D. Molecular tuning of electroreception in sharks and skates.Nature. 2018; 558: 122-126Crossref PubMed Scopus (18) Google Scholar]. We propose that pigeons detect magnetic fields by electromagnetic induction within the semicircular canals that is dependent on the presence of apically located voltage-gated cation channels in a population of electrosensory hair cells. We set out to replicate a previous study conducted by Wu and Dickman, who reported that magnetic stimuli induce neuronal activation in the vestibular nuclei of pigeons [5Wu L.Q. Dickman J.D. Magnetoreception in an avian brain in part mediated by inner ear lagena.Curr. Biol. 2011; 21: 418-423Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. To perform this experiment within the laboratory environment, we built a room constructed of mu metal surrounded by an aluminum Faraday cage to shield against static and oscillating magnetic fields (Figure 1A). This setup allowed us to perform experiments in a controlled, magnetically clean environment [7Landler L. Nimpf S. Hochstoeger T. Nordmann G.C. Papadaki-Anastasopoulou A. Keays D.A. Comment on “Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans.”.eLife. 2018; 7: e30187Crossref PubMed Scopus (6) Google Scholar]. Magnetic fields were generated using a double-wrapped, custom-built 3D Helmholtz coil system situated in the center of the shielded room (Figure 1B). To reduce movement during the experiments, birds were head fixed using a surgically implanted plastic head post, and the body was immobilized using a 3D printed harness (Figure 1C). We applied the same stimulus as Wu and Dickman, exposing adult pigeons to a 150-μT, rotating magnetic field (n = 22) or to a zero magnetic field (n = 23) for 72 min (Figures 1D–1F) [5Wu L.Q. Dickman J.D. Magnetoreception in an avian brain in part mediated by inner ear lagena.Curr. Biol. 2011; 21: 418-423Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. We performed this experiment both in darkness (n = 30) and under broad-spectrum white light (n = 15). Birds were then perfused, the brains were sliced, and matched sections containing the vestibular nuclei (3 sections per bird) were stained with sera against the neuronal activity marker C-FOS. To minimize variation, all staining was performed simultaneously, all slides were scanned with the same exposure settings, and C-FOS-positive neurons were counted using a machine-learning-based algorithm. Using established anatomical coordinates, we segmented the medial vestibular nuclei (VeM) and compared the density of C-FOS-positive cells of the experimental groups [8Karten H.J. Hodos W. A Stereotaxic Atlas of the Brain of the Pigeon (Columba livia). The Johns Hopkins Press, 1967Google Scholar]. We observed an increase in the density of C-FOS-positive cells in both the light and dark when exposing birds to magnetic fields. In the light, the average density in controls was 35.32 ± 10.20 cells/mm2 (n = 8; mean ± SD) whereas with the magnetic treatment it was 44.38 ± 5.72 cells/mm2 (n = 7; mean ± SD). In the dark, the average density for control birds was 34.70 ± 10.82 cells/mm2 (n = 15; mean ± SD) whereas with the magnetic treatment it was 50.52 ± 27.34 cells/mm2 (n = 15; mean ± SD). An application of a two-way ANOVA revealed a significant effect of the magnetic treatment but no interaction between magnetic treatment and lighting conditions (two-way ANOVA; magnetic: p = 0.0176, F = 6.125; magnetic by light: p = 0.5675, F = 0.332) (Figures 2A and 2B ; Table S1). To explore this in more detail, we employed our spot-detection algorithm coupled to an elastic registration to generate heatmaps showing regional differences in the density of C-FOS-positive cells. This revealed an enrichment of activated neurons in the dorsomedial part of the VeM in animals exposed to magnetic stimuli (Figure 2C). Previous tracing experiments have shown that the dorsomedial VeM is innervated by projections from both the semicircular canals and the otolith organs located in the inner ear [9Dickman J.D. Fang Q. Differential central projections of vestibular afferents in pigeons.J. Comp. Neurol. 1996; 367: 110-131Crossref PubMed Scopus (68) Google Scholar].Figure 2Magnetically Induced Neuronal Activation in the Pigeon Vestibular NucleiShow full caption(A) Representative coronal section stained with sera that bind to the neuronal activity marker C-FOS. Dark-stained nuclei are visible in the inset. Adjacent schematic representation of the pigeon brainstem shows the medial and descending vestibular nuclei (VeM and VeD) in gray [8Karten H.J. Hodos W. A Stereotaxic Atlas of the Brain of the Pigeon (Columba livia). The Johns Hopkins Press, 1967Google Scholar].(B) Quantification of C-FOS-positive cells per mm2 in VeM in birds that were exposed to a rotating magnetic field (MF; n = 22) and to a zero magnetic field control (ZMF; n = 23) (two-way ANOVA; p = 0.0176, F = 6.125). Filled and open circles represent animals that were tested in the dark (n = 15 for ZMF andMF) and in light (n = 8 for ZMF and n = 7 for MF), respectively.(C) Heatmap showing the regional difference in C-FOS cell density in the vestibular nuclei when comparing the MF and ZMF groups. Magnetically responsive neurons were enriched in the dorsomedial region of the VeM.Data are presented as mean ± SD. ∗p < 0.05. Scale bars represent 500 μm (A) and 50 μm (A, inset). VeM, vestibular nucleus medialis; VeD, vestibular nucleus descendens; TTD, nucleus et tractus descendens nervi trigemini; NTS, nucleus tractus solitarius; nIX-X, nucleus nervi glossopharyngei et nucleus motorius dorsalis nervi vagi. See also Table S1.View Large Image Figure ViewerDownload Hi-res image Download (PPT) (A) Representative coronal section stained with sera that bind to the neuronal activity marker C-FOS. Dark-stained nuclei are visible in the inset. Adjacent schematic representation of the pigeon brainstem shows the medial and descending vestibular nuclei (VeM and VeD) in gray [8Karten H.J. Hodos W. A Stereotaxic Atlas of the Brain of the Pigeon (Columba livia). The Johns Hopkins Press, 1967Google Scholar]. (B) Quantification of C-FOS-positive cells per mm2 in VeM in birds that were exposed to a rotating magnetic field (MF; n = 22) and to a zero magnetic field control (ZMF; n = 23) (two-way ANOVA; p = 0.0176, F = 6.125). Filled and open circles represent animals that were tested in the dark (n = 15 for ZMF andMF) and in light (n = 8 for ZMF and n = 7 for MF), respectively. (C) Heatmap showing the regional difference in C-FOS cell density in the vestibular nuclei when comparing the MF and ZMF groups. Magnetically responsive neurons were enriched in the dorsomedial region of the VeM. Data are presented as mean ± SD. ∗p < 0.05. Scale bars represent 500 μm (A) and 50 μm (A, inset). VeM, vestibular nucleus medialis; VeD, vestibular nucleus descendens; TTD, nucleus et tractus descendens nervi trigemini; NTS, nucleus tractus solitarius; nIX-X, nucleus nervi glossopharyngei et nucleus motorius dorsalis nervi vagi. See also Table S1. As we did not observe an interaction between the presence of light and magnetically induced neuronal activation, our results are consistent with a magnetic sensory system based on either magnetite or electromagnetic induction [10Nordmann G.C. Hochstoeger T. Keays D.A. Magnetoreception—a sense without a receptor.PLoS Biol. 2017; 15: e2003234Crossref PubMed Scopus (68) Google Scholar]. We have previously reported the discovery of an iron-rich organelle in both vestibular and cochlear hair cells that is associated with vesicular structures, but because it is primarily composed of ferrihydrite it lacks the magnetic properties to function as the hypothesized torque-based magnetoreceptor [11Lauwers M. Pichler P. Edelman N.B. Resch G.P. Ushakova L. Salzer M.C. Heyers D. Saunders M. Shaw J. Keays D.A. An iron-rich organelle in the cuticular plate of avian hair cells.Curr. Biol. 2013; 23: 924-929Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 12Nimpf S. Malkemper E.P. Lauwers M. Ushakova L. Nordmann G. Wenninger-Weinzierl A. Burkard T.R. Jacob S. Heuser T. Resch G.P. Keays D.A. Subcellular analysis of pigeon hair cells implicates vesicular trafficking in cuticulosome formation and maintenance.eLife. 2017; 6: e29959Crossref PubMed Scopus (9) Google Scholar, 13Jandacka P. Burda H. Pistora J. Magnetically induced behaviour of ferritin corpuscles in avian ears: can cuticulosomes function as magnetosomes?.J. R. Soc. Interface. 2015; 12: 20141087Crossref PubMed Scopus (19) Google Scholar]. Moreover, a systematic screen for magnetite in the pigeon lagena using synchrotron-based X-ray fluorescence microscopy and electron microscopy has failed to identify extra- or intracellular magnetite crystals [14Malkemper E.P. Kagerbauer D. Ushakova L. Nimpf S. Pichler P. Treiber C.D. de Jonge M. Shaw J. Keays D.A. No evidence for a magnetite-based magnetoreceptor in the lagena of pigeons.Curr. Biol. 2019; 29: R14-R15Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. In light of these findings, we focused on electromagnetic induction [15Faraday M. V. Experimental researches in electricity.Philos. Trans. R. Soc. Lond. 1832; 122: 125-162Crossref Google Scholar]. First proposed by Camille Viguier in 1882, this hypothesis predicts that as a terrestrial animal moves through the Earth’s static magnetic field a voltage is induced within the conductive endolymph of the semicircular canals [4Viguier C. Le sens de l’orientation et ses organes chez les animaux et chez l’homme.Rev. Philos. France Let. 1882; : 1-36Google Scholar, 16Jungerman R.L. Rosenblum B. Magnetic induction for the sensing of magnetic fields by animals—an analysis.J. Theor. Biol. 1980; 87: 25-32Crossref PubMed Scopus (24) Google Scholar]. To test the viability of this hypothesis, we built a simple model of a pigeon semicircular canal by filling a plastic tube with artificial pigeon endolymph (see STAR Methods; Figure 3A) [17Sauer G. Richter C.-P. Klinke R. Sodium, potassium, chloride and calcium concentrations measured in pigeon perilymph and endolymph.Hear. Res. 1999; 129: 1-6Crossref PubMed Scopus (19) Google Scholar]. The tubing was closed on both sides with electrodes connected to a nanovoltmeter (forming a loop with a diameter of 21 cm), placed in the center of our magnetic coil system, and exposed to the same rotating magnetic stimulus applied to our birds (i.e., 150 μT rotating 360° with 6°-step changes every 2 s). We observed discrete voltage spikes when the magnetic field stimulus was presented and with each stepwise change (Figure 3B). In accordance with Faraday’s law of electromagnetic induction, we observed the maximum induced voltage (15.6 μV) when the magnetic field vector was perpendicular (90°) to the plane of the canal and lowest (1.6 μV) when the vector was parallel to the plane of the canal (0°) (Figure 3B). In contrast, when presenting the control stimulus (with the current running antiparallel through the double-wrapped coils), we did not observe these characteristic voltage spikes (Figure 3C). Nor did we observe voltage spikes when removing the model of the semicircular canal from the circuit, demonstrating that induction does not occur in the connecting shielded wires (Figure 3D). Next, we measured the dimensions of the semicircular canals in pigeons drawing on previously generated computed tomography (CT) scans (n = 3 birds) [18Malkemper E.P. Mason M.J. Kagerbauer D. Nimpf S. Keays D.A. Ectopic otoconial formation in the lagena of the pigeon inner ear.Biol. Open. 2018; 7: bio034462Crossref PubMed Scopus (2) Google Scholar] (Figure S1A). This revealed that the mean loop diameter of the posterior canal was 4.20 ± 0.01 mm, the anterior canal was 6.37 ± 0.05 mm, and the lateral canal was 5.18 ± 0.15 mm (mean ± SD). Drawing on these measurements and the voltage induced in our 21-cm-diameter model, we were able to estimate the electric field generated within a pigeon’s semicircular canal on presentation of the Wu and Dickman stimulus. We applied the following equation: E=(u/2πr), where E is the electric field, r is the mean radius of the semicircular canal loop, and u is the measured induced voltage. This revealed a maximal electric field in the anterior canal of 7.2 nV/cm, 5.8 nV/cm for the lateral canal, and 4.7 nV/cm for the posterior canal when applying a rotating 150-μT stimulus. We repeated the aforementioned experiment, applying a 50-μT stimulus, again rotating 360° in 2 min with 6°-step changes every 2 s. This revealed a maximal electric field in the anterior canal of 2 nV/cm, 1.6 nV/cm for the lateral canal, and 1.3 nV/cm for the posterior canal (Figures S1B–S1D). In our experiment, we applied a changing magnetic stimulus to a bird that is head fixed; however, in the natural environment, we imagine that pigeons employ head scanning to alter the orientation of their semicircular canals with respect to the magnetic vector. To assess whether this natural behavior would be sufficient to induce electric fields that are physiologically relevant, we estimated the electric field generated using the following equation, which is derived from Maxwell’s third law: En=B0⋅πf⋅r, where r is the radius of the semicircular canals, B0 is the Earth’s field, and f is the frequency of head scanning [19Feynman R.P. Leighton R.B. Sands M. The Feynman Lectures on Physics, Vol. II: The New Millennium Edition: Mainly Electromagnetism and Matter. Basic Books, 2011Google Scholar]. It has recently been shown that pigeons undertake head scanning during flight that exceeds 700°/s [20Kano F. Walker J. Sasaki T. Biro D. Head-mounted sensors reveal visual attention of free-flying homing pigeons.J. Exp. Biol. 2018; 221: jeb183475Crossref PubMed Scopus (18) Google Scholar]. Based on this frequency and the radii of the semicircular canals reported here, we estimate that natural head movement will generate electric fields in the range of 7.9–9.6 nV/cm in an Earth-strength field (50 μT). Because previous studies have shown that electrosensitive animals can detect fields as small as 5 nV/cm [21Kalmijn A.J. Electric and magnetic field detection in elasmobranch fishes.Science. 1982; 218: 916-918Crossref PubMed Scopus (233) Google Scholar, 22Kalmijn A.J. The electric sense of sharks and rays.J. Exp. Biol. 1971; 55: 371-383Crossref PubMed Google Scholar], we conclude that the Wu and Dickman stimulus and natural head-scanning behavior could induce voltages within the semicircular canals that are within the detectable range of known electrosensory systems. If magnetoreception in pigeons relies on the conversion of magnetic fields into an electric signal, the magnetosensory apparatus might resemble known electroreceptive epithelia on a cellular and molecular level. Ampullae of Lorenzini are electrosensory organs found in cartilaginous fish that consist of specialized sensory cells located at the base of gel-filled canals [22Kalmijn A.J. The electric sense of sharks and rays.J. Exp. Biol. 1971; 55: 371-383Crossref PubMed Google Scholar]. Recent work in little skate (Leucoraja erinacea) has shown that the voltage-sensitive calcium channel CaV1.3/CACNA1D and the large-conductance calcium-activated potassium channel BK/KCNMA1 are enriched in these cells and facilitate electrosensation [23Bellono N.W. Leitch D.B. Julius D. Molecular basis of ancestral vertebrate electroreception.Nature. 2017; 543: 391-396Crossref PubMed Scopus (45) Google Scholar]. Given the ontogenetic proximity of electrosensory, auditory, and vestibular hair cells, we asked whether these electrosensory molecules are present in the pigeon semicircular canals [24Baker C.V.H. Modrell M.S. Insights into electroreceptor development and evolution from molecular comparisons with hair cells.Integr. Comp. Biol. 2018; 58: 329-340Crossref PubMed Scopus (8) Google Scholar]. To function as electroreceptors, we would expect these channels to be apically located in hair cells where they would be exposed to the endolymph (Figures 4A–4C). To test this prediction, we performed fluorescence immunohistochemistry on pigeon ampullary hair cells (n = 3 birds). Staining with sera against the BK channel revealed an enrichment of apical staining in hair cells that are positive for the marker otoferlin (Figures 4D, 4F, 4G, and S2D–S2I) [25Hafidi A. Beurg M. Dulon D. Localization and developmental expression of BK channels in mammalian cochlear hair cells.Neuroscience. 2005; 130: 475-484Crossref PubMed Scopus (67) Google Scholar, 26Roux I. Safieddine S. Nouvian R. Grati M. Simmler M.C. Bahloul A. Perfettini I. Le Gall M. Rostaing P. Hamard G. et al.Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.Cell. 2006; 127: 277-289Abstract Full Text Full Text PDF PubMed Scopus (443) Google Scholar]. Consistent with previous studies, we observed goblet-shaped CaV1.3 staining at hair cell ribbon synapses [27Vincent P.F. Bouleau Y. Charpentier G. Emptoz A. Safieddine S. Petit C. Dulon D. Different CaV1.3 channel isoforms control distinct components of the synaptic vesicle cycle in auditory inner hair cells.J. Neurosci. 2017; 37: 2960-2975Crossref PubMed Scopus (22) Google Scholar] and a punctate enrichment at the apical membrane that has not previously been reported (Figures 4E and 4G). High-resolution confocal imaging further revealed that these CaV1.3-rich plaques are most pronounced at the base of the kinocilium, and that CaV1.3 is localized in the kinocilium itself (Figures S2A–S2C). In sharks and skates, CaV1.3 is characterized by a low threshold of activation attributable to a 10-amino acid lysine-rich insertion located in the intracellular loop between IVS2 and IVS3 of the alpha subunit (Figure 4H). It has been shown that mutating the charged lysine residues in this insertion to neutral glutamine residues results in a channel with a higher threshold for activation [6Bellono N.W. Leitch D.B. Julius D. Molecular tuning of electroreception in sharks and skates.Nature. 2018; 558: 122-126Crossref PubMed Scopus (18) Google Scholar, 23Bellono N.W. Leitch D.B. Julius D. Molecular basis of ancestral vertebrate electroreception.Nature. 2017; 543: 391-396Crossref PubMed Scopus (45) Google Scholar]. Interestingly, Hudspeth and colleagues have reported a similar insertion in CaV1.3 that is expressed in the hair cells of chickens [28Kollmar R. Fak J. Montgomery L.G. Hudspeth A.J. Hair cell-specific splicing of mRNA for the alpha1D subunit of voltage-gated Ca2+ channels in the chicken’s cochlea.Proc. Natl. Acad. Sci. USA. 1997; 94: 14889-14893Crossref PubMed Scopus (64) Google Scholar]. To ascertain whether this charged insertion is expressed in pigeons, we drew on the available genomic resources, determined the gene structure, and designed a PCR-based strategy with primers flanking the putative insertion site (Figures 4H and S3A) [29Holt C. Campbell M. Keays D.A. Edelman N. Kapusta A. Maclary E. Domyan E.T. Suh A. Warren W.C. Yandell M. et al.Improved genome assembly and annotation for the rock pigeon (Columba livia).G3 (Bethesda). 2018; 8: 1391-1398Crossref PubMed Scopus (37) Google Scholar]. We extracted mRNA and generated cDNA libraries for a broad range of tissues from the pigeon including brain, spleen, muscle, retina, basilar papilla, vestibular epithelia, skin, and heart (n = 3 birds). Analysis by gel electrophoresis showed that CaV1.3 is absent in the respiratory concha, muscle, and liver but is otherwise broadly expressed. Strikingly, we only observed PCR products consistent with a larger splice isoform in the cochlea and vestibular system (Figure 4I). Cloning of these PCR products revealed an insertion of 10 amino acids rich in lysine residues with notable homology to that reported in sharks and skates (Figure 4J). We refer to this variant as the KKER splice isoform. In skates it has been shown that CaV1.3 works in conjunction with the BK potassium channel, which has a unique conductance profile due to the expression of an alternatively spliced exon [23Bellono N.W. Leitch D.B. Julius D. Molecular basis of ancestral vertebrate electroreception.Nature. 2017; 543: 391-396Crossref PubMed Scopus (45) Google Scholar]. This variant is distinguished by the presence of an arginine residue at position 340 (R340) and an alanine residue at 347 (A347), which are located intracellularly near the pore of the channel (Figure 4K). We refer to this variant as the RA splice isoform. To ascertain whether this splice isoform is expressed in pigeons, we first determined the genetic architecture of pigeon KCNMA1 (Figure S3B). Drawing on this information, we designed a PCR-based assay that relies on the amplification of exon 9a/b from cDNA libraries, followed by digestion with the restriction enzyme AluI (Figures 4L and S3B). In the event the RA isoform is amplified (exon 9b), the amplicon is resistant to AluI digestion, resulting in the presence of a larger band (239 bp). We found that KCNMA1 is broadly expressed in the pigeon; however, the RA isoform was enriched in the retina and vestibular system. We conclude that the molecular apparatus necessary for the detection of small electric fields is present within the pigeon vestibular apparatus. Finally, we explored the phylogenetic distribution of the splice isoforms of CACNA1D and KCNMA1 among Animalia. To identify CACNA1D homologs containing the long KKER splice isoform, we performed a BLASTp search with a 50-amino-acid-long segment of pigeon CaV1.3, centered around the splice isoform. We found that this insertion first emerged in Gnathostomata and has a limited distribution. It is found in skates, sharks, bats, turtles, rainbow trout, and birds (Figures 4I and S4A). In the case of the KCNMA1 RA isoform, a BLASTp search revealed that it is present in numerous animals including skates, electric eels, numerous fish and many bird species, rodents (including Mus musculus), primates (including Homo sapiens), bats, dolphins, and whales (Figures 4L and S4B). We conclude that the RA splice isoform of KCNMA1 is widely distributed in vertebrates whereas the KKER isoform of CACNA1D is often found in phyla that are known to possess an electric or magnetic sense. In 1882, Viguier speculated that “the geomagnetic field determines, within the endolymph of the canals, induced currents, whose intensities vary dependently of both the canals’ positions in relation to inclination and declination, and the intensity of the magnetic field” [4Viguier C. Le sens de l’orientation et ses organes chez les animaux et chez l’homme.Rev. Philos. France Let. 1882; : 1-36Google Scholar]. In this manuscript, we have explored this hypothesis, one that has largely been ignored by the scientific community since its proposition. We present data that replicates the work of Wu and Dickman, demonstrating magnetically induced neuronal activation in the vestibular nuclei that is not dependent on light. We show that changing low-intensity magnetic stimuli (150 μT) can induce electric fields that lie within the window of physiological detection and that the molecular machinery necessary to detect such fields is present in the pigeon inner ear. Our data are consistent with a model whereby pigeons detect magnetic fields by electromagnetic induction within the semicircular canals relying on the presence of apically located voltage-gated calcium channels in a population of electrosensory hair cells. We have replicated the study of Wu and Dickman with only minor changes to their experimental protocol [5Wu L.Q. Dickman J.D. Magnetoreception in an avian brain in part mediated by inner ear lagena.Curr. Biol. 2011; 21: 418-423Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar]. Specifically, we employed double-wrapped coils to control for heat and vibration when delivering the magnetic stimuli and a plastic head post and glue in preference to metal screws to head fix the bird and conducted the experiment in both darkness and light. We have further been able to refine the region activated by magnetic stimuli by elastic registration and mapping of C-FOS-positive cells to the dorsomedial part of the VeM. Our results, coupled with the initial study, support the contention that the vestibular system is involved in processing magnetic information in the absence of light. Wu and Dickman had argued that the primary sensors likely reside in the lagena, because extirpation of the cochlear duct abolished magnetically induced activity in the vestibular nuclei. These results, however, are also consistent with magnetosensation by electromagnetic induction, because removal of the cochlear duct would compromise the integrity of the entire endolymphatic system and its ionic constituents. Magnetosensation by induction has only been considered viable in elasmobranch fish, because surface-electrosensitive epithelia could detect voltages induced a" @default.
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• W2985445317 title "A Putative Mechanism for Magnetoreception by Electromagnetic Induction in the Pigeon Inner Ear" @default.
• W2985445317 cites W1956289694 @default.
• W2985445317 cites W1967071295 @default.
• W2985445317 cites W1967128502 @default.
• W2985445317 cites W1972485929 @default.
• W2985445317 cites W1977597294 @default.
• W2985445317 cites W1985349430 @default.
• W2985445317 cites W1992321695 @default.
• W2985445317 cites W1997193727 @default.
• W2985445317 cites W1998172473 @default.
• W2985445317 cites W2011415025 @default.
• W2985445317 cites W2033770285 @default.
• W2985445317 cites W2035735944 @default.
• W2985445317 cites W2042722342 @default.
• W2985445317 cites W2070411645 @default.
• W2985445317 cites W2073276800 @default.
• W2985445317 cites W2078577861 @default.
• W2985445317 cites W2096331940 @default.
• W2985445317 cites W2109355282 @default.
• W2985445317 cites W2136518918 @default.
• W2985445317 cites W2138668594 @default.
• W2985445317 cites W2151318440 @default.
• W2985445317 cites W2167222809 @default.
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