iPSC-derived GABAergic Neuron Generation Service

GABAergic neurons are a class of inhibitory neurons that release the neurotransmitter gamma-aminobutyric acid (GABA). GABA is the primary inhibitory neurotransmitter in the adult central nervous system and plays a crucial role in regulating neuronal excitability and maintaining the balance between neuronal excitation and inhibition.

These inhibitory neurons can be derived from human induced pluripotent stem cells (iPSCs) through specific differentiation protocols. iPSCs are stem cells generated by reprogramming somatic cells back into a pluripotent state. The pluripotent iPSCs can then be directed to differentiate into GABAergic neuron precursors that mature into functional inhibitory neurons.

iPSC-derived GABAergic Neurons Offer Unique Advantages

• Model inhibitory neuron deficits underlying neurological conditions

Patient-specific iPSC lines allow the generation of GABAergic neurons carrying disease-relevant genetic backgrounds to model inhibitory dysfunction.

• Obtain homogeneous populations of GABAergic neurons

Differentiation from iPSC lines can produce pure cultures of defined GABAergic neuron types.

• Investigate GABAergic neurodevelopment and interneuron subtype specification

The developmental paths of iPSC-derived GABAergic neurons can be studied to understand interneuron fate determination and maturation.

• Reconstruct inhibitory neural circuits from patient cells

Co-cultures of GABAergic and glutamatergic neurons derived from the same patient enable modeling of imbalanced neural networks.

• Screen compounds modulating GABA receptors/transporters

iPSC-derived GABAergic neurons are useful for high-throughput screening of drugs targeting GABA pathways like anticonvulsants.

Key Applications Include

• Modeling GABAergic neuron pathology in epilepsy, autism, schizophrenia.
• Studying neurodevelopmental disorders with interneuron migration defects.
• Evaluating effects of anesthetics/sedatives targeting GABA receptors.
• Screening antiepileptic, anxiolytic, or neuropsychiatric therapeutics.

Common Assays With iPSC-derived GABAergic Neurons

• Immunocytochemistry for Neuron markers, GABA, Vesicular Transporters

Utilizes antibodies to confirm GABAergic identity, visualize GABA production, and examine synaptic machinery localization.

• Gene Expression Analysis (RNA-seq, qPCR)

Transcriptomic studies to analyze gene expression patterns related to GABAergic development, specification, and function.

• Morphology and Neurodevelopmental Assessments

Evaluates neurite outgrowth, migration, synaptic connectivity, and maturation of GABAergic neuron cultures.

• Electrophysiology (Patch-clamp, multi-electrode arrays)

Measures electrical properties of GABA neurons and quantifies inhibitory synaptic currents via electrode recordings.

• Calcium Imaging And Fluorescence Neurotransmitter Assays

Uses fluorescent GABA sensors and calcium dyes to visualize GABAergic neurotransmission and neuronal firing activity.

GABAergic Neuron Dysfunction Has Been Implicated In

• Epilepsy: Reduced GABA inhibition contributes to seizures.

Mutations in genes involved in GABA synthesis, release, or GABA receptor function can lead to neuronal hyperexcitability and epileptic seizures. iPSC models allow for studying patient-specific GABAergic neuron defects.

• Schizophrenia: GABA neuron deficits involved in cognitive symptoms.

Post-mortem studies of schizophrenia patient brains have revealed deficits in cortical GABAergic interneurons, which may underlie cognitive impairments. iPSC models enable the investigating of interneuron developmental defects.

• Autism Spectrum Disorder: GABAergic signaling disruptions.

Imbalances between excitatory/inhibitory neurotransmission, with reduced GABAergic signaling, have been observed in autism. iPSC models can reconstruct imbalanced neural networks from patients.

• Down Syndrome: Altered GABA system development.

The extra copy of chromosome 21 in Down syndrome impacts the expression of genes involved in GABAergic interneuron development and specification, contributing to cognitive deficits.

• Huntington's Disease: Mutant huntingtin impairs GABA function.

The mutant huntingtin protein can cause transcriptional dysregulation of GABA synthesis enzymes and transporters, impairing GABAergic neurotransmission in the brain.

Patient-derived iPSC models allow the investigation of GABAergic neuron phenotypes related to these disorders. Genomic screening, CRISPR gene editing, and compound treatments can probe underlying pathways and validate therapeutic targets.

In summary, iPSC-derived GABAergic neurons enable neuroscience research into inhibitory circuits, neurodevelopmental disorders, and GABA-targeted therapeutics. Creative Biolabs offers custom GABAergic neuron differentiation services utilizing your cell lines. Let us guide you through your experimental investigations and help advance your understanding of neural development and connectivity.

Reference

1. Staege, Selma et al. "Reduced Expression of GABA A Receptor Alpha2 Subunit Is Associated With Disinhibition of DYT-THAP1 Dystonia Patient-Derived Striatal Medium Spiny Neurons." Front Cell Dev Biol. 2021;9:650586. Distributed under Open Access license CC BY 4.0. The original image was modified.