Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation
Ye Ji KimNoah KentEmmanuel Vargas PaniaguaNicolette DriscollAnthony TabetFlorian KoehlerElian MalkinEthan FreyMarie MantheyAtharva SahasrabudheTaylor M. CannonKeisuke NagaoDavid MankusMargaret E. BisherGiovanni de NolaAbigail K. R. Lytton‐JeanLorenzo SignorelliDanijela GregurećPolina Anikeeva
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Abstract Deep brain stimulation with implanted electrodes has transformed neuroscience studies and treatment of neurological and psychiatric conditions. Discovering less invasive alternatives to deep brain stimulation could expand its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials has been explored as a means for remote neuromodulation. Here we synthesize magnetoelectric nanodiscs (MENDs) with a core–double-shell Fe 3 O 4 –CoFe 2 O 4 –BaTiO 3 architecture (250 nm diameter and 50 nm thickness) with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg mm −2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization that, combined with cable theory, supports our observations in vitro and informs magnetoelectric stimulation in vivo. Injected into the ventral tegmental area or the subthalamic nucleus of genetically intact mice at concentrations of 1 mg ml −1 , MENDs enable remote control of reward or motor behaviours, respectively. These findings set the stage for mechanistic optimization of magnetoelectric neuromodulation towards applications in neuroscience research.Keywords:
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Chronic Deep Brain Stimulation (DBS), which was approved for the treatment of symptoms in Parkinson Disease in 1998, is a conceptually new tool in the field of Neuromodulation. DBS is fundamentally similar to most pharmacological neuro modulation therapies: Both modulate synaptic transmission between nerve cells by modulating the release and/or effectivity of neurotransmitters in synapses. The highly specific functional modulation of brain structures in DBS opens new avenues for Neuromodulation in e.g. epilepsy and psychiatric diseases. Clinical application of DBS (Activa /spl reg/ Therapy), although in the large majority of the patients clinically highly effective, shows a wide range of outcomes. Maturation and standardization of the DBS therapy are required to bring DBS up to "standard of medical care". This paper will address the main concepts of the DBS therapy: Neuroanatomical stereotactic imaging and neurphysio logical brain target identification as well as further research and development to bring this therapy up to standard of medical care.
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Deep Brain Stimulation (DBS) is a developing therapeutic technique with a high potential to control and treat central nervous system diseases through neuromodulation. DBS utilizes through implanted electrodes that are inserted in the targeted brain structure. Being an emerging technology; neuromodulation introduces many challenges that are not yet comprehensively identified, characterized and resolved. The advancement of this technique requires qualitative and quantitative perception of the brain response to electrical stimulation which is controlled by the electric field distribution within the brain tissue. This can be realized by formulating the tissue-field interaction such that we will have a better understanding of the spatial extent and the direct effects of deep brain stimulation (DBS) on neurons activity. The focus of this research is to develop a model for encoding and decoding the neuron activity in the DBS region and to address all the parameters that affect this activity in order to have a complete understanding of the DBS problem and to develop a brain model that can be readily used in DBS analysis. Our goal is to study the immediate direct effects of the stimulating field and examine where the beneficial effects of DBS originate since the mechanism of DBS is not yet fully understand and hence an inclusive comprehensive performance study will be done for the DBS problem.
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Abstract The method of optogenetics has spread widely in neurobiology over the past 10 years and has found extensive application in various fields of this sciences. It allows to control and regulate cellular activity with high spatial and temporal resolution. In this study, optogenetic activation was applied to astrocytes expressing ChR2. Optogenetic stimulation parameters were determined, in which the frequency of spontaneous currents of hippocampal pyramidal neurons significantly changed. In the future, it is planned to use the obtained data on the modes of optogenetic stimulation of astrocytes to normalize the functions of the hippocampus in mice-models of Alzheimer’s disease.
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Deep brain stimulation (DBS) refers to a neurosurgical process in which electrical stimulation is delivered via electrodes implanted within deep brain regions. DBS has become the most established clinical therapy for patients with movement disorders, although recent studies have investigated its application in a broad range of neurological and psychiatric disorders as well. Moreover, DBS has proven effective in controlling symptoms in patients with Parkinson's disease (PD). While early DBS systems were capable of stimulation only, technological advancements have allowed for the direct assessment of dysfunctional brain activity and subsequent stimulation of the pathological circuitry. DBS can also be combined with neurochemical stimulation to address decreased concentrations of dopamine in the brain. Given that both electrical and neurochemical treatments for PD aim to rectify abnormalities in neural activity, the general term "neuromodulation" is considered more accurate and comprehensive. Recent improvements in signal detection and information processing techniques have provided further insight into PD mechanisms, which may aid in the development of personalized biomarkers and in the prediction of symptoms. In this comprehensive review, we discuss various aspects of neuromodulation in patients with PD, including basic theories, stimulation paradigms, and current challenges in the field.
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