Many brain disorders exhibit altered synapse formation in development or synapse loss with age. To understand the complexities of human synapse development and degeneration, scientists now engineer neurons and brain organoids from human-induced pluripotent stem cells (hIPSC). These hIPSC-derived brain models develop both excitatory and inhibitory synapses and functional synaptic activity. In this review, we address the ability of hIPSC-derived brain models to recapitulate synapse development and insights gained into the molecular mechanisms underlying synaptic alterations in neuronal disorders. We also discuss the potential for more accurate human brain models to advance our understanding of synapse development, degeneration, and therapeutic responses.
Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines
Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia: a postmortem morphometric study
Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies
KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner
A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells
Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes
Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons
Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells
Stimulation of GABA-induced Ca2+ influx enhances maturation of human induced pluripotent stem cell-derived neurons
Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders
Selective inhibition of KCC2 leads to hyperexcitability and epileptiform discharges in hippocampal slices and in vivo
The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2
Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture
Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions
Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation
Reversal of Phenotypic Abnormalities by CRISPR/Cas9-Mediated Gene Correction in Huntington Disease Patient-Derived Induced Pluripotent Stem Cells
A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells
Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder
Multi-level characterization of balanced inhibitory-excitatory cortical neuron network derived from human pluripotent stem cells
A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research
Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells
Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments
Reproducible and efficient generation of functionally active neurons from human hiPSCs for preclinical disease modeling
Striatal neurons directly converted from Huntington's disease patient fibroblasts recapitulate age-associated disease phenotypes
APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer's Disease Phenotypes in Human iPSC-Derived Brain Cell Types
α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies
Visualizing the Synaptic and Cellular Ultrastructure in Neurons Differentiated from Human Induced Neural Stem Cells-An Optimized Protocol
Alpha-synuclein dynamics in induced pluripotent stem cell-derived dopaminergic neurons from a Parkinson's disease patient (PARK4) with SNCA triplication.
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