Christina Porras , Hayden Olliviere , Sean P. Bradley , Alice M. Graham , Yogita Chudasama , Tracey A. Rouault
{"title":"Ablation of Iron Regulatory Protein 2 produces a neurological disorder characterized by motor, somatosensory, and executive dysfunction in mice","authors":"Christina Porras , Hayden Olliviere , Sean P. Bradley , Alice M. Graham , Yogita Chudasama , Tracey A. Rouault","doi":"10.1016/j.crneur.2024.100136","DOIUrl":"10.1016/j.crneur.2024.100136","url":null,"abstract":"<div><p>Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient's neurodegenerative disorder.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X24000135/pdfft?md5=b6f5d363d8ae486e87477cbbc1eec1f3&pid=1-s2.0-S2665945X24000135-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xindong Song (宋欣东) , Yueqi Guo (郭月琪) , Chenggang Chen , Jong Hoon Lee , Xiaoqin Wang
{"title":"Tonotopic organization of auditory cortex in awake marmosets revealed by multi-modal wide-field optical imaging","authors":"Xindong Song (宋欣东) , Yueqi Guo (郭月琪) , Chenggang Chen , Jong Hoon Lee , Xiaoqin Wang","doi":"10.1016/j.crneur.2024.100132","DOIUrl":"https://doi.org/10.1016/j.crneur.2024.100132","url":null,"abstract":"<div><p>Tonotopic organization of the auditory cortex has been extensively studied in many mammalian species using various methodologies and physiological preparations. Tonotopy mapping in primates, however, is more limited due to constraints such as cortical folding, use of anesthetized subjects, and mapping methodology. Here we applied a combination of through-skull and through-window intrinsic optical signal imaging, wide-field calcium imaging, and neural probe recording techniques in awake marmosets (<em>Callithrix jacchus</em>), a New World monkey with most of its auditory cortex located on a flat brain surface. Coarse tonotopic gradients, including a recently described rostral-temporal (RT) to parabelt gradient, were revealed by the through-skull imaging of intrinsic optical signals and were subsequently validated by single-unit recording. Furthermore, these tonotopic gradients were observed with more detail through chronically implanted cranial windows with additional verifications on the experimental design. Moreover, the tonotopy mapped by the intrinsic-signal imaging methods was verified by wide-field calcium imaging in an AAV-GCaMP labeled subject. After these validations and with further effort to expand the field of view more rostrally in both windowed and through-skull subjects, an additional putative tonotopic gradient was observed more rostrally to the area RT, which has not been previously described by the standard model of tonotopic organization of the primate auditory cortex. Together, these results provide the most comprehensive data of tonotopy mapping in an awake primate species with unprecedented coverage and details in the rostral proportion and support a caudal-rostrally arranged mesoscale organization of at least three repeats of functional gradients in the primate auditory cortex, similar to the ventral stream of primate visual cortex.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"6 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X24000093/pdfft?md5=fea4da7e18db6dc2892c92b8ad81bd78&pid=1-s2.0-S2665945X24000093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chrysa Retsa , Ana Hernando Ariza , Nathanael W. Noordanus , Lorenzo Ruffoni , Micah M. Murray , Benedetta Franceschiello
{"title":"A psychophysically-tuned computational model of human primary visual cortex produces geometric optical illusions","authors":"Chrysa Retsa , Ana Hernando Ariza , Nathanael W. Noordanus , Lorenzo Ruffoni , Micah M. Murray , Benedetta Franceschiello","doi":"10.1016/j.crneur.2024.100140","DOIUrl":"10.1016/j.crneur.2024.100140","url":null,"abstract":"<div><div>Geometric optical illusions (GOIs) are mismatches between physical stimuli and perception. GOIs provide an access point to study the interplay between sensation and perception, Yet, there is relatively scant quantitative investigation of the extent to which different GOIs rely on similar or distinct perceptual mechanisms, which themselves are driven by specific physical properties. We addressed this knowledge gap with a combination of psychophysics and computational modelling. First, 30 healthy adults reported quantitatively their perceptual biases with three GOIs, whose physical properties parametrically varied on a trial-by-trial basis. A given physical property, when considered in isolation, had different effects on perceptual biases depending on the GOI (e.g. the spacing of stimuli affected one GOI, but not another). For a given GOI, there were oftentimes interactions between the effects of different physical properties. Next, we used these psychophysical results to tune a computational model of primary visual cortex that combines parameters of orientation selectivity, receptive-field size, intra-cortical connectivity, and long-range interactions. We showed that similar biases generated <em>in-silico</em> mirror those observed in human behavior when receptive field size, bandwidth and shape (rounded or elongated) are tuned, as well as parameters encoding the strength of the long-range intra-regional interactions between receptive fields. Collectively, our results suggest that different physical properties are not operating independently, but rather synergistically, to generate a GOI. Such results provide a roadmap whereby computational modelling, informed by human psychophysics, can reveal likely mechanistic underpinnings of perception.</div></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deyl Djama , Florian Zirpel , Zhiwen Ye , Gerald Moore , Charmaine Chue , Christopher Edge , Polona Jager , Alessio Delogu , Stephen G. Brickley
{"title":"The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons","authors":"Deyl Djama , Florian Zirpel , Zhiwen Ye , Gerald Moore , Charmaine Chue , Christopher Edge , Polona Jager , Alessio Delogu , Stephen G. Brickley","doi":"10.1016/j.crneur.2024.100130","DOIUrl":"https://doi.org/10.1016/j.crneur.2024.100130","url":null,"abstract":"<div><p>A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron's selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"6 ","pages":"Article 100130"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X2400007X/pdfft?md5=13640fc8035938aff360c3363c819995&pid=1-s2.0-S2665945X2400007X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular mechanisms of cooperative context-sensitive predictive inference","authors":"Tomáš Marvan , William A. Phillips","doi":"10.1016/j.crneur.2024.100129","DOIUrl":"https://doi.org/10.1016/j.crneur.2024.100129","url":null,"abstract":"<div><p>We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"6 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X24000068/pdfft?md5=7f131b904d5d497ab2591177a7d6de61&pid=1-s2.0-S2665945X24000068-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140605348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarina D. Milicevic , Brianna L. Barbeau , Darko D. Lovic , Aayushi A. Patel , Violetta O. Ivanova , Srdjan D. Antic
{"title":"Physiological features of parvalbumin-expressing GABAergic interneurons contributing to high-frequency oscillations in the cerebral cortex","authors":"Katarina D. Milicevic , Brianna L. Barbeau , Darko D. Lovic , Aayushi A. Patel , Violetta O. Ivanova , Srdjan D. Antic","doi":"10.1016/j.crneur.2023.100121","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100121","url":null,"abstract":"<div><p>Parvalbumin-expressing (PV+) inhibitory interneurons drive gamma oscillations (30–80 Hz), which underlie higher cognitive functions. In this review, we discuss two groups/aspects of fundamental properties of PV+ interneurons. In the first group (dubbed <em>Before Axon</em>), we list properties representing optimal synaptic integration in PV+ interneurons designed to support fast oscillations. For example: [i] Information can neither enter nor leave the neocortex without the engagement of fast PV+ -mediated inhibition; [ii] Voltage responses in PV+ interneuron dendrites integrate linearly to reduce impact of the fluctuations in the afferent drive; and [iii] Reversed somatodendritic Rm gradient accelerates the time courses of synaptic potentials arriving at the soma. In the second group (dubbed <em>After Axon</em>), we list morphological and biophysical properties responsible for (a) short synaptic delays, and (b) efficient postsynaptic outcomes. For example: [i] Fast-spiking ability that allows PV+ interneurons to outpace other cortical neurons (pyramidal neurons). [ii] Myelinated axon (which is only found in the PV+ subclass of interneurons) to secure fast-spiking at the initial axon segment; and [iii] Inhibitory autapses – autoinhibition, which assures brief biphasic voltage transients and supports postinhibitory rebounds. Recent advent of scientific tools, such as viral strategies to target PV cells and the ability to monitor PV cells via in vivo imaging during behavior, will aid in defining the role of PV cells in the CNS. Given the link between PV+ interneurons and cognition, in the future, it would be useful to carry out physiological recordings in the PV+ cell type selectively and characterize if and how psychiatric and neurological diseases affect initiation and propagation of electrical signals in this cortical sub-circuit. Voltage imaging may allow fast recordings of electrical signals from many PV+ interneurons simultaneously.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"6 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X23000499/pdfft?md5=9e950352f24d5acad413acd54cc81f76&pid=1-s2.0-S2665945X23000499-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139503938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John W. McLean , Mary VanHart , Madilyn P. McWilliams , Charlene B. Farmer , David K. Crossman , Rita M. Cowell , Julie A. Wilson , Scott M. Wilson
{"title":"Analysis of the neuromuscular deficits caused by STAM1 deficiency","authors":"John W. McLean , Mary VanHart , Madilyn P. McWilliams , Charlene B. Farmer , David K. Crossman , Rita M. Cowell , Julie A. Wilson , Scott M. Wilson","doi":"10.1016/j.crneur.2024.100138","DOIUrl":"10.1016/j.crneur.2024.100138","url":null,"abstract":"<div><p>The endosomal sorting complexes required for transport (ESCRT) pathway is composed of a series of protein complexes that are essential for sorting cargo through the endosome. In neurons, the ESCRT pathway is a key mediator of many cellular pathways that regulate neuronal morphogenesis as well as synaptic growth and function. The ESCRT-0 complex, consisting of HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), acts as a gate keeper to this pathway, ultimately determining the fate of the endosomal cargo. We previously showed that a single nucleotide substitution in <em>Hgs</em> results in structural and functional changes in the nervous system of <em>teetering</em> mice. To determine if these changes occurred as a function of HGS's role in the ESCRT pathway and its association with STAM1, we investigated if STAM1 deficiency also leads to a similar impairment of the nervous system. In contrast to <em>teetering</em> mice that die within 5 weeks of age and exhibit reduced body mass, 1-month-old <em>Stam1</em> knockout mice were not visibly different from controls. However, by 3 months of age, STAM1 deficiency caused reduced muscle mass, strength, and motor performance. These changes in motor function did not correlate with either a loss in motor neuron number or abnormal myelination of peripheral nerves. Instead, the motor endplate structure was altered in the <em>Stam1</em> knockout mice by 1 month of age and continued to degenerate over time, correlating with a significant reduction in muscle fiber size and increased expression of the embryonic γ acetylcholine receptor (AChR) subunit at 3 months of age. There was also a significant reduction in the levels of two presynaptic SNARE proteins, VTI1A and VAMP2, in the motor neurons of the <em>Stam1</em> knockout mice. As loss of STAM1 expression replicates many of the structural changes at the motor endplates that we have previously reported with loss of HGS, these results suggest that the HGS/STAM1 complex plays a critical role in maintaining synaptic structure and function in the mammalian nervous system.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"7 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X24000159/pdfft?md5=46d5a077507b2083cc1a8239a5a26d10&pid=1-s2.0-S2665945X24000159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the development of human voice perception: Neurobiological mechanisms and pathophysiology","authors":"Emily E. Harford , Lori L. Holt , Taylor J. Abel","doi":"10.1016/j.crneur.2024.100127","DOIUrl":"https://doi.org/10.1016/j.crneur.2024.100127","url":null,"abstract":"<div><p>The human voice is a critical stimulus for the auditory system that promotes social connection, informs the listener about identity and emotion, and acts as the carrier for spoken language. Research on voice processing in adults has informed our understanding of the unique status of the human voice in the mature auditory cortex and provided potential explanations for mechanisms that underly voice selectivity and identity processing. There is evidence that voice perception undergoes developmental change starting in infancy and extending through early adolescence. While even young infants recognize the voice of their mother, there is an apparent protracted course of development to reach adult-like selectivity for human voice over other sound categories and recognition of other talkers by voice. Gaps in the literature do not allow for an exact mapping of this trajectory or an adequate description of how voice processing and its neural underpinnings abilities evolve. This review provides a comprehensive account of developmental voice processing research published to date and discusses how this evidence fits with and contributes to current theoretical models proposed in the adult literature. We discuss how factors such as cognitive development, neural plasticity, perceptual narrowing, and language acquisition may contribute to the development of voice processing and its investigation in children. We also review evidence of voice processing abilities in premature birth, autism spectrum disorder, and phonagnosia to examine where and how deviations from the typical trajectory of development may manifest.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"6 ","pages":"Article 100127"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X24000044/pdfft?md5=97cbab561c4db0a0bc469bfbd3a61c9a&pid=1-s2.0-S2665945X24000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140113422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Behavioral optogenetics in nonhuman primates; a psychological perspective.","authors":"Arash Afraz","doi":"10.1016/j.crneur.2023.100101","DOIUrl":"10.1016/j.crneur.2023.100101","url":null,"abstract":"<p><p>Optogenetics has been a promising and developing technology in systems neuroscience throughout the past decade. It has been difficult though to reliably establish the potential behavioral effects of optogenetic perturbation of the neural activity in nonhuman primates. This poses a challenge on the future of optogenetics in humans as the concepts and technology need to be developed in nonhuman primates first. Here, I briefly summarize the viable approaches taken to improve nonhuman primate behavioral optogenetics, then focus on one approach: improvements in the measurement of behavior. I bring examples from visual behavior and show how the choice of method of measurement might conceal large behavioral effects. I will then discuss the \"cortical perturbation detection\" task in detail as an example of a sensitive task that can record the behavioral effects of optogenetic cortical stimulation with high fidelity. Finally, encouraged by the rich scientific landscape ahead of behavioral optogenetics, I invite technology developers to improve the chronically implantable devices designed for simultaneous neural recording and optogenetic intervention in nonhuman primates.</p>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"1 1","pages":"100101"},"PeriodicalIF":0.0,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54048828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristine Marie Yde Ohki , Natalie Monet Walter , Michelle Rickli , José Maria Salazar Campos , Anna Maria Werling , Christian Döring , Susanne Walitza , Edna Grünblatt
{"title":"Protocol for a Wnt reporter assay to measure its activity in human neural stem cells derived from induced pluripotent stem cells","authors":"Cristine Marie Yde Ohki , Natalie Monet Walter , Michelle Rickli , José Maria Salazar Campos , Anna Maria Werling , Christian Döring , Susanne Walitza , Edna Grünblatt","doi":"10.1016/j.crneur.2023.100095","DOIUrl":"10.1016/j.crneur.2023.100095","url":null,"abstract":"<div><p>The canonical Wnt signaling is an essential pathway that regulates cellular proliferation, maturation, and differentiation during neurodevelopment and maintenance of adult tissue homeostasis. This pathway has been implicated with the pathophysiology of neuropsychiatric disorders and was associated with cognitive processes, such as learning and memory. However, the molecular investigation of the Wnt signaling in functional human neural cell lines might be challenging since brain biopsies are not possible and animal models may not represent the polygenic profile of some neurological and neurodevelopmental disorders. In this context, using induced pluripotent stem cells (iPSCs) has become a powerful tool to model disorders that affect the Central Nervous System (CNS) <em>in vitro</em>, by maintaining patients’ genetic backgrounds. In this method paper, we report the development of a virus-free Wnt reporter assay in neural stem cells (NSCs) derived from human iPSCs from two healthy individuals, by using a vector containing a reporter gene (<em>luc2P</em>) under the control of a TCF/LEF (T-cell factor/lymphoid enhancer factor) responsive element. Dose-response curve analysis from this luciferase-based method might be useful when testing the activity of the Wnt signaling pathway after agonists (e.g. Wnt3a) or antagonists (e.g. DKK1) administration, comparing activity between cases and controls in distinct disorders. Using such a reporter assay method may help to elucidate whether neurological or neurodevelopmental mental disorders show alterations in this pathway, and testing whether targeted treatment may reverse these. Therefore, our established assay aims to help researchers on the functional and molecular investigation of the Wnt pathway in patient-specific cell types comprising several neuropsychiatric disorders.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9808372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}