Periodic Reporting for period 2 - NeuroMagMa (The Neurobiology of Magnetic Orientation in Mammals)
Reporting period: 2022-10-01 to 2024-03-31
Many animals use the Earth's magnetic field for orientation, but the sensory cells and molecular mechanisms of the magnetic sense remain a mystery. We tackle this fundamental problem in sensory biology with a top-down approach that exploits state-of-the-art methodology to unravel the neural circuits underlying magnetic orientation. To take advantage of the knowledge and toolkits available for rodent brains, we chose a rodent model organism: Mole-rats, which navigate through a maze of underground tunnels in total darkness for their entire life. Their magnetic sense is well established, and they can be bred in the laboratory.
The project has three aims:
Aim 1: Identify the brain regions involved in magnetoreception. We employ modern techniques to detect neuronal activity on the brain-wide level, such as mapping immediate early genes in cleared brains or functional ultrasound imaging. The goal is to create a global map of the mole-rat brain regions that process magnetic fields.
Aim 2: Discover the neuronal substrate of a magnetic compass using single-unit recordings in brain areas identified in Aim 1 or known to be involved in spatial orientation.
Aim 3: Narrow down the locus of the magnetoreceptive organ. The magnetite theory of magnetoreception predicts it contains magnetite, a strongly magnetic iron oxide. We will meticulously search for the magnetite in the sensory tissues of mole-rats using a spectrum of sensitive methods.
Why does all this matter?
The implications of understanding the magnetic sense go far beyond the satisfaction of scientific curiosity. Here are three examples:
1. Magnetogenetics. If we knew the genes that build mammalian magnetoreceptors, we could express them in neurons to activate them with magnetic fields. In contrast to current optogenetic and chemogenetic approaches, which require implanted fibre optics or drug delivery, magnetic fields penetrate deep tissues non-invasively. Magnetogenetics hold great potential for basic neuroscience and the treatment of neurodegenerative diseases. 2. Do man-made magnetic fields affect wildlife? The 2018 Horizon Scan of Emerging Issues for Global Conservation and Biological Diversity identified this question as one of the most important future issues. An expert panel literature review further concluded that the reported effects of magnetic fields on wildlife lack an understanding of the underlying proximate mechanisms. Deciphering the cellular machinery that allows animals to detect magnetic fields will be key to assessing the wildlife effects of artificial fields in the Anthropocene. 3. Do humans have magnetic cells? The human brain was shown to contain magnetite, but the reasons are unknown. Knowledge of the cellular identity and molecular machinery of mammalian magnetoreceptors will resolve whether the magnetite found in the human brain is part of a magnetic sensory apparatus.
The project has three aims:
Aim 1: Identify the brain regions involved in magnetoreception. We employ modern techniques to detect neuronal activity on the brain-wide level, such as mapping immediate early genes in cleared brains or functional ultrasound imaging. The goal is to create a global map of the mole-rat brain regions that process magnetic fields.
Aim 2: Discover the neuronal substrate of a magnetic compass using single-unit recordings in brain areas identified in Aim 1 or known to be involved in spatial orientation.
Aim 3: Narrow down the locus of the magnetoreceptive organ. The magnetite theory of magnetoreception predicts it contains magnetite, a strongly magnetic iron oxide. We will meticulously search for the magnetite in the sensory tissues of mole-rats using a spectrum of sensitive methods.
Why does all this matter?
The implications of understanding the magnetic sense go far beyond the satisfaction of scientific curiosity. Here are three examples:
1. Magnetogenetics. If we knew the genes that build mammalian magnetoreceptors, we could express them in neurons to activate them with magnetic fields. In contrast to current optogenetic and chemogenetic approaches, which require implanted fibre optics or drug delivery, magnetic fields penetrate deep tissues non-invasively. Magnetogenetics hold great potential for basic neuroscience and the treatment of neurodegenerative diseases. 2. Do man-made magnetic fields affect wildlife? The 2018 Horizon Scan of Emerging Issues for Global Conservation and Biological Diversity identified this question as one of the most important future issues. An expert panel literature review further concluded that the reported effects of magnetic fields on wildlife lack an understanding of the underlying proximate mechanisms. Deciphering the cellular machinery that allows animals to detect magnetic fields will be key to assessing the wildlife effects of artificial fields in the Anthropocene. 3. Do humans have magnetic cells? The human brain was shown to contain magnetite, but the reasons are unknown. Knowledge of the cellular identity and molecular machinery of mammalian magnetoreceptors will resolve whether the magnetite found in the human brain is part of a magnetic sensory apparatus.
We have set up recordings from the hippocampus in freely moving mole-rats and discovered the first spatially tuned neurons. Furthermore, we have created a mole-rat reference brain and we are currently optimizing our pipeline to map sensory induced brain activity. Finally, we have searched for iron-based magnetoreceptor cells in the mole-rat eye using iron staining, elemental mapping at Synchrotrons, microCT, and magnetic resonance imaging.
For the first time, we report recordings from spatially tuned neurons in the mole-rat hippocampus. By the end of the project, we expect to know how these are tuned and whether the Earth's magnetic field plays a role in their tuning.
Furthermore, by the end of the project, we expect to know if magnetite-based magnetoreceptors are present in mole-rat eyes.
Furthermore, by the end of the project, we expect to know if magnetite-based magnetoreceptors are present in mole-rat eyes.