Our brain is composed of over 100 billion neurons, which form an even larger number of brain circuits. Technology that can precisely control brain circuits is essential for uncovering the principles behind advanced brain functions such as behavior, cognition, and emotions, as well as for identifying mechanisms of various neurological diseases and developing treatments. Furthermore, replicating brain networks with greater accuracy could be applied to develop new AI algorithms, increasing the significance of brain function enhancement technologies in modern science.

A prominent example is Neuralink, led by Elon MUSK, which has made a considerable impact on modern neuroscience by demonstrating the existence of numerous neurons and brain circuits using techniques that activate brain signals with electrical signals and control brain activity through optogenetics. However, since these techniques involve invasive, wired methods that require electrode or light source insertion into the brain, they have been challenging to apply clinically and have not been used to treat actual brain diseases. Consequently, there have been attempts to remotely control brain circuits wirelessly using magnetic fields, which are highly penetrative and safe for biological tissues.

In particular, a technique proposed in 2016 involves expressing magnetic receptors in neurons by linking ferritin, a magnetic protein, to ion channels that respond to force or heat. This method aims to control the opening and closing of ion channels through forces or heat generated by ferritin in response to magnetic fields. However, multiple research teams could not replicate consistent results with this technique, possibly due to insufficient magnetism in ferritin to activate ion channels through magnetic force.

Developing Magnetogenetics by Connecting Magnetic Nanoparticles to Ion Channels

Some animals, such as migratory birds and salmon, detect the Earth's magnetic field to navigate. This phenomenon, known as magnetoreception, is regulated by magnetoreceptors, though their exact nature remains unclear. As such, magnetogenetics—a technology for controlling cellular signals with magnetic fields—has long been a challenging issue in the scientific community.

The Institute for Basic Science (IBS) Center for Nanomedicine combined nanotechnology and genetic engineering to create nano-magnetoreceptors in animal brain cells. They developed a "nano-magnetogenetic" technology to wirelessly and remotely control neural circuits and brain signals with precision using magnetic fields. With this technology, they successfully regulated animal emotions and behaviors, and its potential application in humans could lead to groundbreaking advances in treating neurological disorders.

The research team developed a magnetic nanoparticle called "m-Torquer" that responds to weak rotating magnetic fields, producing a force of approximately 2 pN (picoNewtons). This nanoparticle binds to the receptor on the neuron surface and exerts force on the mechanosensitive ion channel Piezo-1. The torque force generated in response to the rotating magnetic field created by a magnetic device opens the Piezo-1 ion channel, promoting calcium influx and modulating neural signal activation.

[Figure 1] Neuron signal control using nano-magnetogenetics
A method of controlling cell activation using gene delivery to create force-sensitive ion channels in cells, combined with magnetic nanoparticles and magnetic fields (IBS Center for Nanomedicine, Nature Materials, 2021).

Second-Generation Magnetogenetics: Precision Control of Brain Circuits with “Nano-MIND”

Taking it a step further, the research team developed the Nano-MIND (Magnetogenetic Interface for NeuroDynamics) technology, which enables precise wireless and remote control of specific brain circuits using magnetic fields, successfully regulating advanced brain functions such as animal emotions, sociality, and motivation. Notably, when they selectively activated inhibitory GABA brain circuits in the medial preoptic area, responsible for maternal behaviors, they could modulate emotions and social behaviors. Mice with activated maternal behavior circuits, even those that were not mother mice, showed significantly increased caregiving behavior, such as bringing young mice into their nests.

Additionally, brain circuits governing appetite, which increases when we are hungry, could also be regulated. When they remotely activated inhibitory neurons in the lateral hypothalamus, which governs motivation brain circuits, appetite and feeding behavior doubled. Conversely, activating excitatory neurons to suppress motivation circuits halved appetite and feeding behavior.

Through such methods, magnetogenetic technology has revealed mechanisms for improving memory, emotions, and cognitive abilities, particularly enabling selective activation of desired brain circuits to bidirectionally regulate advanced brain functions. By understanding the roles and operating principles of various brain circuits, the technology could contribute to essential artificial neural network construction for neuroscience research, potentially advancing AI technology.

[Figure 2] Future brain science innovation through nano-magnetogenetics and Nano-MIND technology
Nano-MIND technology allows selective control of specific neuron and brain circuit signals, enabling wireless, remote modulation of living animals’ behavior and emotions via magnetic fields. Activating maternal behavior brain circuits increased maternal care in mother mice (IBS Center for Nanomedicine, Nature Nanotechnology, 2024).

Clinical Potential of Magnetogenetics: Treating Neurological Disorders

The research team developed the “Nano-Magnetogenetic-Driven Deep Brain Stimulation (MMG-DBS)” to activate deep brain neurons with magnetic fields, confirming its effectiveness in treating Parkinson's disease. When applied to a Parkinson’s rat model with motor impairments, the technology improved balance and motor function by over twice, nearly restoring normal motor abilities. This non-invasive technique that precisely stimulates neurons alleviated Parkinson's symptoms more effectively than traditional DBS methods. This approach also holds promise for studying other neurological disorders caused by abnormal neuron and brain signal activation, such as epilepsy and Alzheimer’s disease.

Establishing and Leading the Field of Nano-Neuroscience

The research team is innovatively advancing neuroscience with nanoscience. Specifically, by using magnetic fields in brain-computer interfaces (BCI), they became the first to control brain circuits worldwide, with the potential to intricately map complex brain networks, laying the groundwork for constructing artificial neural networks and developing advanced AI algorithms. Additionally, it offers new treatments for various intractable brain diseases, such as Parkinson's and Alzheimer's, and may also be used to identify causes and develop treatments for mental illnesses, such as addiction and depression.

[Figure 3] Characteristics and clinical applicability of nano-magnetogenetics
Nano-magnetogenetics enables remote wireless stimulation deep into the human brain, allowing selective control of signals at the single-neuron level. With its high precision and meter-range operational distance, it holds promise for human applications.

참고문헌

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