Neurodevelopmental Disorders
neurodevelopmental disorders
Georgia Panagiotakos
Looking for a supportive, dynamic and inclusive environment to do cutting edge science? The Panagiotakos Lab at Mount Sinai has two postdoctoral positions open! Links for both positions below – come join us if you love neural development, ion channels or anything in between! The Panagiotakos Lab, in the Departments of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York, is seeking postdoctoral fellows (recently completed Ph.D., M.D. or M.D./Ph.D.) with expertise in calcium imaging, electrophysiology, developmental neuroscience, stem cell biology, and/or genomics/sequencing approaches to study cellular and molecular mechanisms that underlie the acquisition of cell fate during mammalian brain development. Dr. Panagiotakos’ team combines multiple complementary approaches, including genetic mouse models, calcium imaging, fluorescence microscopy, pharmacology, cortical slice cultures, and various omics and biochemical analyses, to interrogate roles for calcium signaling, electrical activity, ion channel splice isoforms, and disease risk genes during normal development and in the context of neuropsychiatric disorders of developmental origin. The qualified candidates will use cutting-edge cellular/molecular biology, imaging and sequencing approaches in these studies, including long-isoform sequencing, CUT&RUN, and live imaging, to investigate the impact and mechanistic underpinnings of disease-relevant ion channels and calcium signaling on cellular events during brain development, including proliferation, migration, neurogenesis and gliogenesis.
Dr. Amir Aly
Applications are invited for three-year PhD studentships at the University of Plymouth, UK. The studentships will start on Wednesday 1 October 2025. A list of projects can be found below. It is essential that candidates discuss their proposal/plans with their intended supervisor(s), prior to writing their proposal and submitting an application. The school can only consider PhD research proposals that have the support of a supervisor. The projects include: 1. AI-Based Analysis of Voice Biomarkers in Neurodevelopmental Disorders, 2. Virtual Reality Training for Spatial Familiarity with Autistic Individuals, 3. Enhancing Social Interaction for Autistic Individuals through Anthropomorphic Augmented Reality, 4. Examining Cohesion and Authoritarianism through Synchronised VR Interactions, 5. Pure Fantasy: Harnessing VR to Explore and Enhance the Ideal Self in Autistic Individuals, 6. Board games for autistic wellbeing.
Lorenzo Fontolan
We are pleased to announce the opening of a PhD position at INMED (Aix-Marseille University) through the SCHADOC program, focused on the neural coding of social interactions and memory in the cortex of behaving mice. The project will investigate how social behaviors essential for cooperation, mating, and group dynamics are encoded in the brain, and how these processes are disrupted in neurodevelopmental disorders such as autism. This project uses longitudinal calcium imaging and population-level data analysis to study how cortical circuits encode social interactions in mice. Recordings from mPFC and S1 in wild-type and Neurod2 KO mice will be used to extract neural representations of social memory. The candidate will develop and apply computational models of neural dynamics and representational geometry to uncover how these codes evolve over time and are disrupted in social amnesia.
Cellular Crosstalk in Brain Development, Evolution and Disease
Cellular crosstalk is an essential process during brain development and is influenced by numerous factors, including cell morphology, adhesion, the local extracellular matrix and secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the proper development of the human brain. Therefore, we combine 2D and 3D in vitro human models to better understand the molecular and cellular mechanisms involved in progenitor proliferation and fate, migration and maturation of excitatory and inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders.
Gene regulatory mechanisms of neocortex development and evolution
The neocortex is considered to be the seat of higher cognitive functions in humans. During its evolution, most notably in humans, the neocortex has undergone considerable expansion, which is reflected by an increase in the number of neurons. Neocortical neurons are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behaviour of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development and evolution, neural stem cell regulation and neurodevelopmental disorders.
Virtual and experimental approaches to the pathogenicity of SynGAP1 missense mutations
Targeting gamma oscillations to improve cognition
SYNGAP1 Natural History Study/ Multidisciplinary Clinic at Children’s Hospital Colorado
Beyond the synapse: SYNGAP1 in primary and motile cilia
The Roles of Distinct Functions of SynGAP1 in SYNGAP1-Related Disorders
Modeling human brain development and disease: the role of primary cilia
Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.
Contrasting developmental principles of human brain development and their relevance to neurodevelopmental disorders
Cortical interneurons from brain development to disease
Cellular crosstalk in Neurodevelopmental Disorders
Cellular crosstalk is an essential process during brain development and it is influenced by numerous factors, including the morphology of the cells, their adhesion molecules, the local extracellular matrix and the secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the correct development of the human brain. Hence, we combine the in vivo mouse model and the in vitro human-derived neurons, cerebral organoids, and dorso-ventral assembloids in order to better comprehend the molecular and cellular mechanisms involved in ventral progenitors’ proliferation and fate as well as migration and maturation of inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders. We particularly focus on mutations in genes influencing cell-cell contacts, extracellular matrix, and secretion of vesicles and therefore study intrinsic and extrinsic mechanisms contributing to the formation of the brain. Our data reveal an important contribution of cell non-autonomous mechanisms in the development of neurodevelopmental disorders.
Quantifying perturbed SynGAP1 function caused by coding mutations
Therapeutic Strategies for Autism: Targeting Three Levels of the Central Dogma of Molecular Biology with a Focus on SYNGAP1
Involvement of the brain endothelium in neurodevelopmental disorders
Circuit mechanisms of attention dysfunction in Scn8a+/- mice: implications for epilepsy and neurodevelopmental disorders
Catatonia in Neurodevelopmental Conditions
The balanced brain: two-photon microscopy of inhibitory synapse formation
Coordination between excitatory and inhibitory synapses (providing positive and negative signals respectively) is required to ensure proper information processing in the brain. Many brain disorders, especially neurodevelopental disorders, are rooted in a specific disturbance of this coordination. In my research group we use a combination of two-photon microscopy and electrophisiology to examine how inhibitory synapses are fromed and how this formation is coordinated with nearby excitatroy synapses.
Precision Genomics in Neurodevelopmental Disorders
A Data-Driven Approach to Reconstructing Disease Trajectories in SYNGAP1-Related Disorders
Harnessing mRNA metabolism for the development of precision gene therapy
Linking SYNGAP1 with Human-Specific Mechanisms of Neuronal Development
SYNGAP1 and Epilepsy SurgerySYNGAP1 and Epilepsy Surgery
Developmental disorders of presynaptic vesicle cycling - Synaptotagmin-1 and beyond
Post-diagnostic research on rare genetic developmental disorders presents new opportunities (and a few challenges) for discovery neuroscience and translation. In this talk, Kate will describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence pre-synaptic vesicle cycling (SVC disorders). She will focus on Synaptotagmin-1 Associated Neurodevelopmental Disorder (also known as Baker Gordon Syndrome), first described in 2015 and now diagnosed in more than 50 children and young people worldwide. She will then present work-in-progress by her group on the neurodevelopmental spectrum of SVC disorders more broadly, and discuss opportunities for collaborative neuroscience which can bridge the gaps between genetic cause and complex neurological, cognitive and mental health outcomes.
Baby steps to breakthroughs in precision health in neurodevelopmental disorders
Targeting alternative splicing of SYNGAP1 using antisense oligonucleotides
Functional and translational implications of A-to-I editing in brain development and neurodevelopmental disorders
Investigating activity-dependent processes in cerebral cortex development and disease
The cerebral cortex contains an extraordinary diversity of excitatory projection neuron (PN) and inhibitory interneurons (IN), wired together to form complex circuits. Spatiotemporally coordinated execution of intrinsic molecular programs by PNs and INs and activity-dependent processes, contribute to cortical development and cortical microcircuits formation. Alterations of these delicate processes have often been associated to neurological/neurodevelopmental disorders. However, despite the groundbreaking discovery that spontaneous activity in the embryonic brain can shape regional identities of distinct cortical territories, it is still unclear whether this early activity contributes to define subtype-specific neuronal fate as well as circuit assembly. In this study, we combined in utero genetic perturbations via CRISPR/Cas9 system and pharmacological inhibition of selected ion channels with RNA-sequencing and live imaging technologies to identify the activity-regulated processes controlling the development of different cortical PN classes, their wiring and the acquisition of subtype specific features. Moreover, we generated human induced pluripotent stem cells (iPSCs) form patients affected by a severe, rare and untreatable form of developmental epileptic encephalopathy. By differentiating cortical organoids form patient-derived iPSCs we create human models of early electrical alterations for studying molecular, structural and functional consequences of the genetic mutations during cortical development. Our ultimate goal is to define the activity-conditioned processes that physiologically occur during the development of cortical circuits, to identify novel therapeutical paths to address the pathological consequences of neonatal epilepsies.
Don't forget the gametes: Neurodevelopmental pathogenesis starts in the sperm and egg
Proper development of the nervous system depends not only on the inherited DNA sequence, but also on proper regulation of gene expression, as controlled in part by epigenetic mechanisms present in the parental gametes. In this presentation an internationally recognized research advocate explains why researchers concerned about the origins of increasingly prevalent neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder should look beyond genetics in probing the origins of dysregulated transcription of brain-related genes. The culprit for a subset of cases, she contends, may lie in the exposure history of the parents, and thus their germ cells. To illustrate how environmentally informed, nongenetic dysfunction may occur, she focuses on the example of parents' histories of exposure to common agents of modern inhalational anesthesia, a highly toxic exposure that in mammalian models has been seen to induce heritable neurodevelopmental abnormality in offspring born of exposed germline.
How are nervous systems remodeled in complex metazoans?
Early in development the nervous system is constructed with far too many neurons that make an excessive number of synaptic connections. Later, a wave of neuronal remodeling radically reshapes nervous system wiring and cell numbers through the selective elimination of excess synapses, axons and dendrites, and even whole neurons. This remodeling is widespread across the nervous system, extensive in terms of how much individual brain regions can change (e.g. in some cases 50% of neurons integrated into a brain circuit are eliminated), and thought to be essential for optimizing nervous system function. Perturbations of neuronal remodeling are thought to underlie devastating neurodevelopmental disorders including autism spectrum disorder, schizophrenia, and epilepsy. This seminar will discuss our efforts to use the relatively simple nervous system of Drosophila to understand the mechanistic basis by which cells, or parts of cells, are specified for removal and eliminated from the nervous system.
2nd In-Vitro 2D & 3D Neuronal Networks Summit
The event is open to everyone interested in Neuroscience, Cell Biology, Drug Discovery, Disease Modeling, and Bio/Neuroengineering! This meeting is a platform bringing scientists from all over the world together and fostering scientific exchange and collaboration.
2nd In-Vitro 2D & 3D Neuronal Networks Summit
The event is open to everyone interested in Neuroscience, Cell Biology, Drug Discovery, Disease Modeling, and Bio/Neuroengineering! This meeting is a platform bringing scientists from all over the world together and fostering scientific exchange and collaboration.
Mapping the Dynamics of the Linear and 3D Genome of Single Cells in the Developing Brain
Three intimately related dimensions of the mammalian genome—linear DNA sequence, gene transcription, and 3D genome architecture—are crucial for the development of nervous systems. Changes in the linear genome (e.g., de novo mutations), transcriptome, and 3D genome structure lead to debilitating neurodevelopmental disorders, such as autism and schizophrenia. However, current technologies and data are severely limited: (1) 3D genome structures of single brain cells have not been solved; (2) little is known about the dynamics of single-cell transcriptome and 3D genome after birth; (3) true de novo mutations are extremely difficult to distinguish from false positives (DNA damage and/or amplification errors). Here, I filled in this longstanding technological and knowledge gap. I recently developed a high-resolution method—diploid chromatin conformation capture (Dip-C)—which resolved the first 3D structure of the human genome, tackling a longstanding problem dating back to the 1880s. Using Dip-C, I obtained the first 3D genome structure of a single brain cell, and created the first transcriptome and 3D genome atlas of the mouse brain during postnatal development. I found that in adults, 3D genome “structure types” delineate all major cell types, with high correlation between chromatin A/B compartments and gene expression. During development, both transcriptome and 3D genome are extensively transformed in the first month of life. In neurons, 3D genome is rewired across scales, correlated with gene expression modules, and independent of sensory experience. Finally, I examined allele-specific structure of imprinted genes, revealing local and chromosome-wide differences. More recently, I expanded my 3D genome atlas to the human and mouse cerebellum—the most consistently affected brain region in autism. I uncovered unique 3D genome rewiring throughout life, providing a structural basis for the cerebellum’s unique mode of development and aging. In addition, to accurately measure de novo mutations in a single cell, I developed a new method—multiplex end-tagging amplification of complementary strands (META-CS), which eliminates nearly all false positives by virtue of DNA complementarity. Using META-CS, I determined the true mutation spectrum of single human brain cells, free from chemical artifacts. Together, my findings uncovered an unknown dimension of neurodevelopment, and open up opportunities for new treatments for autism and other developmental disorders.
One by one: brain organoid modelling of neurodevelopmental disorders at single cell resolution
The use of milk exosomes to increase the expression of SYNGAP1 expression in SYNGAP1 mice
An Introduction to Autism BrainNet
Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries
GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease. Our web pages for reference: https://devneuro.org.uk/marinlab/ & https://devneuro.org.uk/rico/default
Translational Biomarkers in Preclinical Models of Neurodevelopmental Disorders
Synaptic alterations in the striatum drive ASD-related behaviors in mice
Role of primary visual cortex (V1) in visual awareness: insights from blindsight
Stem cell approaches to understand acquired and genetic epilepsies
The Hsieh lab focuses on the mechanisms that promote neural stem cell self-renewal and differentiation in embryonic and adult brain. Using mouse models, video-EEG monitoring, viral techniques, and imaging/electrophysiological approaches, we elucidated many of the key transcriptional/epigenetic regulators of adult neurogenesis and showed aberrant new neuron integration in adult rodent hippocampus contribute to circuit disruption and seizure development. Building on this work, I will present our recent studies describing how GABA-mediated Ca2+ activity regulates the production of aberrant adult-born granule cells. In a new direction of my laboratory, we are using human induced pluripotent stem cells and brain organoid models as approaches to understand brain development and disease. Mutations in one gene, Aristaless-related homeobox (ARX), are of considerable interest since they are known to cause a common spectrum of neurodevelopmental disorders including epilepsy, autism, and intellectual disability. We have generated cortical and subpallial organoids from patients with poly-alanine expansion mutations in ARX. To understand the nature of ARX mutations in the organoid system, we are currently performing cellular, molecular, and physiological analyses. I will present these data to gain a comprehensive picture of the effect of ARX mutations in brain development. Since we do not understand how human brain development is affected by ARX mutations that contribute to epilepsy, we believe these studies will allow us to understand the mechanism of pathogenesis of ARX mutations, which has the potential to impact the diagnosis and care of patients.
Networking—the key to success… especially in the brain
In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you can’t befriend everybody you meet, nor can every neuron wire with every other!). This talk will cover some of Alex’s work showing that microscopic (cellular scale) brain networks inferred from spontaneous activity show similar complex topology to that previously described in macroscopic human brain scans. The talk will also discuss what happens when neurodevelopment is disrupted in the case of a monogenic disorder called Rett Syndrome. This will include simulations of neuronal activity and the effects of manipulation of model parameters as well as what happens when we manipulate real developing networks using optogenetics. If functional development can be restored in atypical networks, this may have implications for treatment of neurodevelopmental disorders like Rett Syndrome.
Investigating the functional single-cell biology of SynGAP1 pathways
Dual lecture: Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries
GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.
Mechanisms of CACNA1A-associated developmental epileptic encephalopathies
Developmental epileptic encephalopathies are early-onset epilepsies, often refractory to therapy, with developmental delay or regression. These disorders carry poor neurodevelopmental prognosis, with long-term refractory epilepsy and persistent cognitive, behavioral and motor deficits. Mutations in the CACNA1A gene, encoding the pore-forming α1 subunit of CaV2.1 voltage-gated calcium channels, result in a spectrum of neurological disorders, including severe, early-onset epileptic encephalopathies. Recent work from the Rossignol lab helped characterize the phenotypic spectrum of CACNA1A-related epilepsies in humans. Using conditional genetics and novel animal models, the Rossignol lab unveiled some of the underlying pathophysiological mechanisms, including critical deficits in cortical inhibition, resulting in seizures and a range of cognitive-behavioral deficits. Importantly, Dr. Rossignol’s team demonstrated that the targeted activation of specific GABAergic interneuron populations in selected cortical regions prevents motor seizures and reverts attention deficits and cognitive rigidity in mouse models of the disorder. These recent findings open novel avenues for the treatment of these severe CACNA1A-associated neurodevelopmental disorders.
Relearning to see with a damaged V1
Behavioral phenotyping strategies for mouse models of neurodevelopmental disorders
Gestational exposure to environmental toxins, infections, and stressors are epidemiologically linked to neurodevelopmental disorders
Gestational exposure to environmental toxins, infections, and stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism spectrum disorder. We modeled some of these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly dysregulated the maternal immune system. Male but not female offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions, along with disruptions of gut structure and microbiome composition. Cellularly, prenatal stressors impaired microglial synaptic pruning in males during early postnatal development. Precise inhibition of microglial phagocytosis during the same critical period mimicked the impact of prenatal stressors on the male-specific social deficits. Conversely, modifying the gut microbiome rescued the social and cellular deficits, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development, perhaps via a gut-brain disruption.
Untitled Seminar
Interpretation of SYNGAP1 Variants
Careers in neuroscience (and beyond!)
Join us to hear about degrees and careers in neuroscience, what it’s like to be a neuroscientist, the wide range of career options open to you after a neuroscience degree, first-hand examples of career paths in neuroscience, and some tips and thoughts to help you in your own careers. This free and friendly webinar will give you the chance to ask questions from people with different experiences in neuroscience: - Emma Soopramanien, the BNA Committee Representative for Students and Early Career Researchers – Emma has just completed her undergraduate course in neuroscience, and will be hosting the webinar. - Professor Anthony Isles, BNA Trustee – Anthony is a professor at Cardiff University, where he researches epigenetic mechanisms of brain and behaviour and how they contribute to neurodevelopmental and neuropsychiatric disorders, as well as teaching undergraduate and postgraduate students. He will talk about how he came to be a neuroscientist researcher and ways into neuroscience. - Dr Anne Cooke, BNA Chief Executive – Anne studied physiology and neuroscience at university and carried out research into neuronal communication, before then following a career path with roles in academia and industry, and now as CE at the BNA. Anne will describe her own career in neuroscience, as well as some of the many other options open to you after a neuroscience degree.
Learning under uncertainty in autism and anxiety
Optimally interacting with a changeable and uncertain world requires estimating and representing uncertainty. Psychiatric and neurodevelopmental conditions such as anxiety and autism are characterized by an altered response to uncertainty. I will review the evidence for these phenomena from computational modelling, and outline the planned experiments from our lab to add further weight to these ideas. If time allows, I will present results from a control sample in a novel task interrogating a particular type of uncertainty and their associated transdiagnostic psychiatric traits.
Types of seizures and EEG patterns in SYNGAP1
Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids
The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes—in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points.
Male-specific intracellular signaling and male bias in neurodevelopmental disorders
Sensory Processing and Arousal in Neurodevelopmental Disorders
Modulating gene regulation to treat gene dosage-associated diseases
Synapse and Circuit Development
The symposium will start with A/Prof Jenny Gunnersen who will present “New insights into mechanisms of excitatory synapse development”. Then, Dr Tommas Ellender will deal with the “Embryonic neural progenitor pools and the generation of fine-scale neural circuits” and Dr Thomas Marissal will talk about “Parvalbumin interneurons: the missing link between the micro and macroscopic alterations related to neurodevelopmental disorders?"”.
New Strategies and Approaches to Tackle and Understand Neurological Disorder
Broadly, the Mauro Costa-Mattioli laboratory (The MCM Lab) encompasses two complementary lines of research. The first one, more traditional but very important, aims at unraveling the molecular mechanisms underlying memory formation (e.g., using state-of-the-art molecular and cell-specific genetic approaches). Learning and memory disorders can strike the brain during development (e.g., Autism Spectrum Disorders and Down Syndrome), as well as during adulthood (e.g., Alzheimer’s disease). We are interested in understanding the specific circuits and molecular pathways that are primarily targeted in these disorders and how they can be restored. To tackle these questions, we use a multidisciplinary, convergent and cross-species approach that combines mouse and fly genetics, molecular biology, electrophysiology, stem cell biology, optogenetics and behavioral techniques. The second line of research, more recent and relatively unexplored, is focused on understanding how gut microbes control CNS driven-behavior and brain function. Our recent discoveries, that microbes in the gut could modulate brain function and behavior in a very powerful way, have added a whole new dimension to the classic view of how complex behaviors are controlled. The unexpected findings have opened new avenues of study for us and are currently driving my lab to answer a host of new and very interesting questions: - What are the gut microbes (and metabolites) that regulate CNS-driven behaviors? Would it be possible to develop an unbiased screening method to identify specific microbes that regulate different behaviors? - If this is the case, can we identify how members of the gut microbiome (and their metabolites) mechanistically influence brain function? - What is the communication channel between the gut microbiota and the brain? Do different gut microbes use different ways to interact with the brain? - Could disruption of the gut microbial ecology cause neurodevelopmental dysfunction? If so, what is the impact of disruption in young and adult animals? - More importantly, could specific restoration of selected bacterial strains (new generation probiotics) represent a novel therapeutic approach for the targeted treatment of neurodevelopmental disorders? - Finally, can we develop microbiota-directed therapeutic foods to repair brain dysfunction in a variety of neurological disorders?
The time of chromatin: emerging insights from longitudinal modelling of neurodevelopmental disorders
Sensory brain responses alterations as translational markers for SynGAP1 haploinsufficiency
Developmental trajectories of sleep EEG in neurodevelopmental disorders: Does sex matter?
FENS Forum 2024
Functional characterization of DPYSL5 gene variants involved in neurodevelopmental disorders with brain malformations
FENS Forum 2024
Human iPSC-derived neurons to investigate subtype-specific alterations in neurodevelopmental disorders: Our progress on SSADH deficiency
FENS Forum 2024
Integrating network activity with transcriptomic profiling in hiPSCs-derived neuronal networks to understand the molecular drivers of functional heterogeneity in the context of neurodevelopmental disorders
FENS Forum 2024
Investigating the pathogenic potential of KCNH5 variants in neurodevelopmental disorders
FENS Forum 2024
Investigating the pathogenic potential of CLSTN1 variants in neurodevelopmental disorders
FENS Forum 2024
PTCHD1 modulates cytoskeleton remodeling through regulation of Rac1-PAK signaling pathway, consistent with neurodevelopmental disorders phenotype
FENS Forum 2024
Rabphilin 3A: From NMDA receptor synaptic retention to neurodevelopmental disorders
FENS Forum 2024
Role of astrocytes in visual synaptic transmission and plasticity: Implications in neurodevelopmental disorders
FENS Forum 2024
The true cost of air pollution on neurodevelopmental disorders: Postnatal PM10 exposure impairs normal development in transgenic ApoE mice
FENS Forum 2024
In vivo xenotransplantation of patient iPSC-derived neurons in MECP2 neurodevelopmental disorders
FENS Forum 2024