Order Neurons Research Articles

Differential target multiplexed spinal cord stimulation in patients with Persistent Spinal Pain Syndrome Type II: a study protocol for a 12-month multicentre cohort study (DETECT)

IntroductionDifferential target multiplexed spinal cord stimulation (DTM SCS) is a new stimulation paradigm for chronic pain management with the aim of modulating glial cells and neurons in order to rebalance...

Multi-Characteristic Opsin Therapy to Functionalize Retina, Attenuate Retinal Degeneration, and Restore Vision in Mouse Models of Retinitis Pigmentosa.

Retinal degeneration 1 and 10 (rd1 and rd10) mice are useful animal models of retinitis pigmentosa (RP) with rapidly and slowly progressive pathologies, respectively. Our study aims were to determine the effect of adeno-associated viral vector 2 (AAV2)-delivered multi-characteristic opsin (MCO-010; under the control of a metabotropic glutamate receptor-6 promoter enhancer) on the morphological and functional characteristics of vision in both rd1 and rd10 mice. Various retinal measures of MCO-010 transduction and electrophysiological, behavioral, and other routine blood analyses were performed in the rd1 and/or rd10 mice after intravitreal injection of 1µL of MCO-010 or AAV2 vehicle. Functional tests included electroretinogram, visually evoked potential, and behavior assay (optomotor and water maze). Retinal thickness, intraocular pressure, and plasma cytokine levels were also determined. Following intravitreal MCO-010 injection, approximately 80% of bipolar cells were transduced in the retina, and no alterations in retinal thickness were observed at 4months post-injection. However, retinal thickness significantly decreased in control mice. MCO-010 treatment increased head movements and induced faster navigation of mice to the platform in a water-maze test. The MCO-010 gene therapy helped preserve visually evoked electrical response in the retina and visual cortex. No ocular toxicity, immunotoxicity, or phototoxicity was observed in the MCO-010-treated mice, even under chronic intense light conditions. Intravitreal MCO-010 was well tolerated in rd1 and rd10 mice models of RP, and it appeared to attenuate retinal photoreceptor degeneration based on retinal structure and functional outcome measures. As reported here, optogenetic treatment of the inner retina attenuates further retinal degeneration in addition to photosensitizing higher order neurons, and this disease-modifying aspect should be evaluated in optogenetic clinical trials.

Nonlinear Decoupling Control With PIλ Dμ Neural Network for MIMO Systems.

In this brief, a fractional order proportional-integral-differential neural network (PIDNN) controller based on the beetle swarm optimization algorithm (BSO-PI [Formula: see text]NN) is proposed for multi-input multi-output (MIMO) systems with strong coupling. First, the fractional order PID operator is introduced to the hidden layer neurons of the neural network, where long memory characteristics of the fractional order neurons can improve the control accuracy and convergence speed. Second, a sufficient condition on the learning rate is established to ensure the stability of the controller by the Lyapunov theory. Third, the PI [Formula: see text]NN is initialized by the BSO algorithm to prevent weights from falling into local optima. The proposed fractional order PIDNN controller can eliminate the coupling between variables and achieve desirable control performance without specific system models. To the authors' best knowledge, this is the first work that the fractional order PI [Formula: see text] neurons are employed in neural network. Two simulation examples verify the effectiveness and superiority of the proposed controller.

Neuromorphic Sensor Based on Force-Sensing Resistors.

This work introduces a neuromorphic sensor (NS) based on force-sensing resistors (FSR) and spiking neurons for robotic systems. The proposed sensor integrates the FSR in the schematic of the spiking neuron in order to make the sensor generate spikes with a frequency that depends on the applied force. The performance of the proposed sensor is evaluated in the control of a SMA-actuated robotic finger by monitoring the force during a steady state when the finger pushes on a tweezer. For comparison purposes, we performed a similar evaluation when the SNN received input from a widely used compression load cell (CLC). The results show that the proposed FSR-based neuromorphic sensor has very good sensitivity to low forces and the function between the spiking rate and the applied force is continuous, with good variation range. However, when compared to the CLC, the response of the NS follows a logarithmic-like function with improved sensitivity for small forces. In addition, the power consumption of NS is 128 µW that is 270 times lower than that of the CLC which needs 3.5 mW to operate. These characteristics make the neuromorphic sensor with FSR suitable for bioinspired control of humanoid robotics, representing a low-power and low-cost alternative to the widely used sensors.

Oxytocin-receptor-expressing neurons in the lateral parabrachial nucleus activate widespread brain regions predominantly involved in fluid satiation

Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (OxtrPBN) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of OxtrPBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of OxtrPBN neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating OxtrPBN neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders.

NEUROMARKETING APPROACH IN TOURISM SECTOR

Neuromarketing is the field of science in which the methods of neuroscience discipline are used in marketing studies. Factors such as the inadequacy of traditional marketing methods, the development of technology and the awareness of consumers have necessitated marketers to develop new ideas. Advertising studies and marketing strategies are developed by revealing the factors that are effective in the subconscious of consumers with neuroimaging methods and analyzing the results. Neuromarketing examines the interaction of neurons in order to explain the purchasing behavior of consumers. This field, which is directly related to the human brain, can identify issues that consumers do not want to say or avoid telling the truth. This study was prepared to investigate the science of neuromarketing and to explain the structure and functions of the human brain. The study was prepared by document analysis method, which is one of the qualitative research methods. A literature review was conducted using secondary data on neuromarketing and the human brain. The study was completed by examining books, journals, articles, master's and doctoral theses, and internet resources on related topics. Neuromarketing techniques are used in many fields such as advertising and film industry, branding, pricing, brand positioning, entertainment industry and tourism. As a result of research; it is seen that the history of neuromarketing science dates back to about 50 years ago. In this case, neuromarketing is a new and developing science. In the researches conducted, it has been determined that there are insufficient studies on the subject in the tourism sector. This research aims to reveal a different area where neuromarketing can be applied in the tourism sector by examining the studies on the human brain and neuromarketing. Considering the data obtained, suggestions are made in the conclusion and evaluation section

Trophoblast glycoprotein is required for efficient synaptic vesicle exocytosis from retinal rod bipolar cells.

Rod bipolar cells (RBCs) faithfully transmit light-driven signals from rod photoreceptors in the outer retina to third order neurons in the inner retina. Recently, significant work has focused on the role of leucine-rich repeat (LRR) proteins in synaptic development and signal transduction at RBC synapses. We previously identified trophoblast glycoprotein (TPBG) as a novel transmembrane LRR protein localized to the dendrites and axon terminals of RBCs. We examined the effects on RBC physiology and retinal processing of TPBG genetic knockout in mice using immunofluorescence and electron microscopy, electroretinogram recording, patch-clamp electrophysiology, and time-resolved membrane capacitance measurements. The scotopic electroretinogram showed a modest increase in the b-wave and a marked attenuation in oscillatory potentials in the TPBG knockout. No effect of TPBG knockout was observed on the RBC dendritic morphology, TRPM1 currents, or RBC excitability. Because scotopic oscillatory potentials primarily reflect RBC-driven rhythmic activity of the inner retina, we investigated the contribution of TPBG to downstream transmission from RBCs to third-order neurons. Using electron microscopy, we found shorter synaptic ribbons in TPBG knockout axon terminals in RBCs. Time-resolved capacitance measurements indicated that TPBG knockout reduces synaptic vesicle exocytosis and subsequent GABAergic reciprocal feedback without altering voltage-gated Ca2+ currents. TPBG is required for normal synaptic ribbon development and efficient neurotransmitter release from RBCs to downstream cells. Our results highlight a novel synaptic role for TPBG at RBC ribbon synapses and support further examination into the mechanisms by which TPBG regulates RBC physiology and circuit function.

A Novel Methodology Based on a Deep Neural Network and Data Mining for Predicting the Segmental Voltage Drop in Automated Guided Vehicle Battery Cells

AGVs are important elements of the Industry 4.0 automation process. The optimization of logistics transport in production environments depends on the economical use of battery power. In this study, we propose a novel deep neural network-based method and data mining for predicting segmented AGV battery voltage drop. The experiments were performed using data from the Formica 1 AGV of AIUT Ltd., Gliwice, Poland. The data were converted to a one-second resolution according to the OPCUA open standard. Pre-processing involved using an analysis of variance to detect any missing data. To do this, the standard deviation, variance, minimum and maximum values, range, linear deviation, and standard deviation were calculated for all of the permitted sigma values in one percent increments. Data with a sigma exceeding 1.5 were considered missing and replaced with a smoothed moving average. The correlation dependencies between the predicted signals were determined using the Pearson, Spearman, and Kendall correlation coefficients. Training, validation, and test sets were prepared by calculating additional parameters for each segment, including the count number, duration, delta voltage, quality, and initial segment voltage, which were classified into static and dynamic categories. The experiments were performed on the hidden layer using different numbers of neurons in order to select the best architecture. The length of the “time window” was also determined experimentally and was 12. The MAPE of the short-term forecast of seven segments and the medium-term forecast of nine segments were 0.09% and 0.18%, respectively. Each study duration was up to 1.96 min.

Analysis of neural network connections based on memristors and their multiple offset phenomena

The article suggests a construction method of a magnetron memristor connecting a three-dimensional Hopfield neural network and a Rulkov neuron in order to build a more complex and achieve more bio-like neural network properties, which has rarely been proposed before. It is discovered that the dynamical behavior of this high-dimensional neural network system is rich, and that the system exhibits many dynamical behaviors depending on the parameter changes. It is possible to change the attractor’s amplitude and its offset boosting behavior by varying various parameters. Changing the system parameters and modifying the system’s initial value may result in initial offset boosting behavior. Combining nonlinear dynamics research methodologies, such as phase diagram, bifurcation diagram, Lyapunov exponential spectrum, and time series diagram, demonstrates the system’s complex dynamical behavior. By analyzing the system complexity and random sequence test, we found that the system has the characteristics of large complexity and strong pseudo-randomness. Eventually, the hardware realizability is proved by the construction of the DSP platform.

Cutaneous allodynia as predictor for treatment response in chronic migraine: a cohort study

BackgroundCentral sensitisation is an important mechanism in migraine chronification. It is presumed to occur in second and third order neurons sequentially, resulting in an analogous spatial distribution of cutaneous allodynia with cephalic and extracephalic symptoms. We investigated whether allodynia, and its subtypes based on spatial distribution and type of stimulus, predict response to treatment in chronic migraine patients.MethodsThis study was conducted as part of the CHARM study (NTR3440), a randomized, double-blind, placebo-controlled trial in chronic migraine patients with medication overuse. We included 173 patients. The presence of cutaneous allodynia at baseline was established with the Allodynia Symptom Checklist. Primary endpoint was reversion from chronic to episodic migraine.ResultsOf all patients, 74.6% reported cutaneous allodynia. Absence of allodynia compared to presence of allodynia was predictive for reversion from chronic to episodic migraine, odds ratio (OR): 2.45 (95% CI: 1.03–5.84), p = 0.042. The predictive value was more pronounced when subdivided for spatial distribution, for participants without allodynia versus cephalic (OR: 4.16 (95% CI: 1.21–14.30), p = 0.024) and extracephalic (OR: 7.32 (95% CI: 1.98- 27.11), p = 0.003) allodynia. Mechanical, but not thermal, allodynia, was associated with outcome.ConclusionsCutaneous allodynia, an important marker for central sensitization, likely has predictive value for treatment response in chronic migraine.Graphical

Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons.

When a muscle is stretched, sensory feedback not only causes reflexes but also leads to a depolarization of sensory afferents throughout the spinal cord (primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensory-evoked PAD is thought to be mediated by a trisynaptic circuit, where sensory input activates first-order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these first-order neurons is unclear. Here, we show that these first-order neurons include propriospinal V3 neurons, as they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents intrinsic to V3 neurons prolong their activity, explaining the prolonged duration of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, helping to explain the radiating nature of PAD. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. In addition, V3 neurons directly innervate proprioceptive afferents (including Ia), causing a glutamate receptor-mediated PAD (glutamate PAD). Finally, increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion.NEW & NOTEWORTHY Locomotor-related propriospinal neurons depolarize sensory axons throughout the spinal cord by either direct glutamatergic axoaxonic contacts or indirect innervation of GABAergic neurons that themselves form axoaxonic contacts on sensory axons. This depolarization (PAD) increases sensory transmission to motoneurons throughout the spinal cord, readying the sensorimotor system for external disturbances. The glutamate-mediated PAD is particularly adaptable, increasing with either an acute block of GABA receptors or chronic spinal cord injury, suggesting a role in motor recovery.

Carotid body contribution to the physio-pathological consequences of intermittent hypoxia: role of nitro-oxidative stress and inflammation.

Obstructive sleep apnoea (OSA), characterized by chronic intermittent hypoxia (CIH), is considered to be an independent risk for hypertension. The pathological cardiorespiratory consequences of OSA have been attributed to systemic oxidative stress, inflammation and sympathetic overflow induced by CIH, but an emerging body of evidence indicates that a nitro-oxidative and pro-inflammatory milieu within the carotid body (CB) is involved in the potentiation of CB chemosensory responses to hypoxia, which contribute to enhance the sympathetic activity. Accordingly, autonomic and cardiovascular alterations induced by CIH are critically dependent on an abnormally heightened CB chemosensory input to the nucleus of tractus solitarius (NTS), where second-order neurons project onto the rostral ventrolateral medulla (RVLM), activating pre-sympathetic neurons that control pre-ganglionic sympathetic neurons. CIH produces oxidative stress and neuroinflammation in the NTS and RVLM, which may contribute to the long-term irreversibility of the CIH-induced alterations. This brief review is mainly focused on the contribution of nitro-oxidative stress and pro-inflammatory molecules on the hyperactivation of the hypoxic chemoreflex pathway including the CB and the brainstem centres, and whether the persistence of autonomic and cardiorespiratory alterations may depend on the glial-related neuroinflammation induced by the enhanced CB chemosensory afferent input.

Saccharin and aspartame excite rat retinal neurons.

Retinal sensitivity to a variety of artificial sweeteners was tested by monitoring changes in internal free calcium in isolated retinal neurons using Fluo3. Several ligands, including aspartame and saccharin elevated internal free calcium. The effects of these ligands were mediated by both ligand-gated membrane channels and G-protein coupled receptors. We explored the receptors responsible for this phenomenon. Surprisingly, mRNA for subunits of the sweet taste receptor dimer (T1R2 and T1R3) were found in retina. Interestingly, knockdown of T1R2 reduced the response to saccharin but not aspartame. But TRPV1 channel antagonists suppressed the responses to aspartame. The results indicate that artificial sweeteners can increase internal free calcium in the retinal neurons through multiple pathways. Furthermore, aspartame reduced the b-wave, but not the a-wave, of the electroretinogram, indicating disruption of communication between photoreceptors and second order neurons.

Dynamic analysis of the discrete fractional-order Rulkov neuron map.

Human evolution is carried out by two genetic systems based on DNA and another based on the transmission of information through the functions of the nervous system. In computational neuroscience, mathematical neural models are used to describe the biological function of the brain. Discrete-time neural models have received particular attention due to their simple analysis and low computational costs. From the concept of neuroscience, discrete fractional order neuron models incorporate the memory in a dynamic model. This paper introduces the fractional order discrete Rulkov neuron map. The presented model is analyzed dynamically and also in terms of synchronization ability. First, the Rulkov neuron map is examined in terms of phase plane, bifurcation diagram, and Lyapunov exponent. The biological behaviors of the Rulkov neuron map, such as silence, bursting, and chaotic firing, also exist in its discrete fractional-order version. The bifurcation diagrams of the proposed model are investigated under the effect of the neuron model's parameters and the fractional order. The stability regions of the system are theoretically and numerically obtained, and it is shown that increasing the order of the fractional order decreases the stable areas. Finally, the synchronization behavior of two fractional-order models is investigated. The results represent that the fractional-order systems cannot reach complete synchronization.

Effects of the gaseous signalling molecule nitroxyl (HNO) on myenteric neurons governing intestinal motility.

The main function of myenteric neurons is the control of gut motility. As we recently showed that nitroxyl (HNO) induces intestinal smooth muscle relaxation, it was of interest to evaluate the effects of this signalling molecule on myenteric neurons in order to distinguish its properties in regard to myocytes. Myenteric neurons isolated from the ileum of 4-10days old rats were used. HNO-induced changes in intracellular concentration of Ca2+ or membrane potential and ion currents were measured using the Ca2+-sensitive fluorescent dye fura-2 AM or by electrophysiological whole-cell recordings, respectively. Changes in intracellular thiol groups pool were evaluated using thiol tracker violet. Angeli's salt was used as HNO donor. The HNO donor Angeli's salt induced a significant increase in the cytosolic Ca2+ concentration at the concentration 50µM and a membrane hyperpolarization from a resting membrane potential of-56.1±8.0mV to-63.1±8.7mV (n=7). Although potassium channels primarily drive membrane potential changes in these cells, outwardly rectifying potassium currents were not significantly affected by 50µM Angeli's salt. Fast inward sodium currents were slightly but not significantly reduced by HNO. In more sensitive cells, HNO tended to reduce the pool of thiol groups. As in the case of smooth muscle cells, HNO causes hyperpolarization of myenteric neurons, an effect also associated with an increase in intracellular Ca2+ concentration. Pathways other than activation of potassium currents appear to drive the hyperpolarization evoked by HNO.

Characterizing the relationship between telomere length and DNA methylation age in induced pluripotent stem cells during neuronal differentiation

AbstractBackgroundInduced pluripotent stem cells (iPSCs) and their resultant neurons are popular models for studying diseases of aging, such as Alzheimer’s disease (AD). One hallmark of aging is the decreasing length of telomeres, the repetitive, protective DNA sequences at the end of each chromosome. We have previously demonstrated that whilst epigenetic age does increase with differentiation, iPSC‐derived neurons still have a fetal DNA methylation profile. It has also been shown by others that telomere length in iPSC‐derived neurons is shorter than the that of the stem cells from which they are derived. However, to our knowledge no one has looked at both epigenetic age and telomere length in the same samples. Therefore, we have collected DNA from different stages of the differentiation of iPSCs into neurons in order to look at the relationship between epigenetic age and telomere length.MethodHuman fibroblast cells were reprogrammed using lentiviral transfection. The resulting iPSC colonies were expanded, differentiated and collected at four different time points: day0 (iPSCs), day16 (neuronal progenitor cells), day37 and day58 (mature neurons). DNA methylation was assessed using the Illumina EPIC array and epigenetic age was derived using both the Horvath skin and blood clock and the Steg fetal brain clock. Absolute telomere length was determined using quantitative real‐time PCR.ResultThis study has identified the telomere dynamics of iPSCs as they undergo differentiation into cortical neurons. Not only this, but by also calculating the epigenetic age in the same samples we have been able to look at the relationship between telomere length and epigenetic age using two differentiation DNA methylation age calculators.ConclusionWe have outlined the relationship between telomere length and DNA methylation age of iPSCs as they differentiate into cortical neurons. This information is important to consider when using iPSCs to model age‐related diseases such as AD.

Bifurcations and Chaos in Three-Coupled Ramp-Type Neurons

The bifurcations and chaos in autonomous systems of two- and three-coupled ramp-type neurons are considered. An asymmetric piecewise linear function is employed for the output function of neurons in order to examine changes in the bifurcations from a sigmoid output function to a ramp output function. Steady solutions in the systems are obtained exactly and they undergo discontinuous bifurcations because the systems are piecewise linear. Periodic solutions and homoclinic/heteroclinic orbits in the systems are obtained by connecting local solutions in linear domains at borders and solving transcendental equations. The bifurcations of the periodic solutions are calculated with the Poincaré maps and the Jacobian matrices, which are also derived rigorously. A stable periodic solution in a two-neuron oscillator of the Wilson–Cowan type with three couplings remains in the case of a ramp neuron. A chaotic attractor of Rössler type emerges in a network of three ramp neurons with six couplings, which is due to two saddle-focuses. The network consists of the two-neuron oscillator and one bypass neuron connected through three couplings. One-dimensional Poincaré maps show the generation of the chaotic attractor through a cascade of period-doubling bifurcations. Further, multiple homoclinic orbits based at a saddle are generated from the destabilization of two focuses when asymmetry in the output function is large. This homoclinicity causes qualitative change in the bifurcations of the periodic solutions as the output function of neurons changes from sigmoid to ramp.

MSP Patches Based Optimized EEG Source Localization and Validation in Visual Cortex of Human Brain

This paper is focused on optimizing EEG source localization of visual neural activities generated in the posterior lobe of the human brain. The visual and neural systems of the human brain process the captured images of faces or scenes into optical and chemical neurons in order to produce electrical potentials over the scalp surface, where EEG electrodes measure these signals to sense the underneath visual brain activity. However, it is categorically hard to localize the true neural sources in the human brain's visual cortex due to overlapping and interaction of other active areas of the lobes of the brain. Thus, a novel algorithm of MSP inversion-based Bayesian framework with varying patches for providing the optimal free energy and minimum location in the visual cortex is proposed to address this issue. This algorithm is integrated with a synthetic EEG dataset generation scheme to validate active neural sources. This proposed algorithm provides satisfactory results in terms of optimal free energy with minimum localization error and validates true active sources in the brain. The SPM12 Toolbox is applied in processing the visual EEG dataset in this research. The application of this proposed algorithm is beneficial in terms of localizing the optimum visual sources and identifying the visual disorders or diseases in the human brain.

Imp and Syp mediated temporal patterning of neural stem cells in the developing Drosophila CNS.

The assembly of complex neural circuits requires that stem cells generate diverse types of neurons in the correct temporal order. Pioneering work in the Drosophila embryonic ventral nerve cord has shown that neural stem cells are temporally patterned by the sequential expression of rapidly changing transcription factors to generate diversity in their progeny. In recent years, a second temporal patterning mechanism, driven by the opposing gradients of the Imp and Syp RNA-binding proteins, has emerged as a powerful way to generate neural diversity. This long-range temporal patterning mechanism is utilized in the extended neural stem cell lineages of the postembryonic fly brain. Here, we review the role played by Imp and Syp gradients in several neural stem cell lineages, focusing on how they specify sequential neural fates through the post-transcriptional regulation of target genes, including the Chinmo and Mamo transcription factors. We further discuss how upstream inputs, including hormonal signals, modify the output of these gradients to couple neurogenesis with the development of the organism. Finally, we review the roles that the Imp and Syp gradients play beyond the generation of diversity, including the regulation of stem cell proliferation, the timing of neural stem cell lineage termination, and the coupling of neuronal birth order to circuit assembly.

A streamlined CRISPR workflow to introduce mutations and generate isogenic iPSCs for modeling amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) represents a complex neurodegenerative disorder with significant genetic heterogeneity. To date, both the genetic etiology and the underlying molecular mechanisms driving this disease remain poorly understood, although in recent years several studies have highlighted a number of genetic mutations causative for ALS. With these mutations pointing to potential pathways that may be affected within individuals with ALS, having the ability to generate human neurons and other disease relevant cells containing these mutations becomes even more critical if new therapies are to emerge. Recent developments with the advent of induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing fields gave us the tools to introduce or correct a specific mutation at any site within the genome of an iPSC, and thus model the specific contribution of risk mutations. In this study we describe a rapid and efficient way to either introduce a mutation into a control line, or to correct an allele-specific mutation, generating an isogenic control line from patient-derived iPSCs with a given mutation. The mutations introduced were the G94A (also known as G93A) mutation into SOD1 or H517Q into FUS, and the mutation corrected was a patient iPSC line with I114T mutation in SOD1. A combination of small molecules and growth factors were used to guide a stepwise differentiation of the edited cells into motor neurons in order to demonstrate that disease-relevant cells could be generated for downstream applications. Through a combination of iPSCs and CRISPR editing, the cells generated here will provide fundamental insights into the molecular mechanisms underlying neuron degeneration in ALS.