Human iPSC-derived GABAergic neurons

Access a toolkit of functional, consistent inhibitory GABAergic neurons in to study neurodegenerative diseases

Powered by opti-ox 

 

GABAergic neurons are the major inhibitory neurons of the central nervous system (CNS), playing a critical role in balancing excitatory signals. This excitatory-inhibitory balance is fundamental to healthy brain function by regulating neuronal firing and network synchronisation. Consequently, dysfunction in GABAergic signalling is strongly associated with neurological and psychiatric disorders, including Alzheimer’s disease, epilepsy, autism spectrum disorder (ASD), and schizophrenia.

Developing therapeutics for these conditions requires reliable, human-relevant models; however, current approaches often struggle to generate inhibitory interneurons with sufficient purity and consistency for high-throughput screening.

ioGABAergic Neurons provide a highly pure (>99%) population of human iPSC-derived inhibitory neurons powered by opti-ox technology. Ready for experimentation within just 4 days of thawing, these cells express classical GABAergic neuron markers and, when in co-culture with glutamatergic neurons, help to modulate neuronal network activity, making them ideal for precisely studying excitatory/inhibitory (E/I) balance and disease mechanisms.

Learn more about ioGABAergic Neurons and explore the data

Learn more about ioGABAergic Neurons and explore the data

ioGABAergic Neurons form a >99% pure inhibitory neuronal population within 4 days post-thaw

 

ioGABAergic Neurons rapidly acquire a homogeneous phenotype, as captured in this video time course. Powered by opti-ox technology, these cells quickly mature into a defined, >99% pure population of GABAergic inhibitory interneurons. Unlike the heterogeneous populations generated by traditional directed differentiation methods, ioGABAergic Neurons provide scientists with a highly pure, human in vitro model to precisely study changes in inhibitory/excitatory balance.

ioGABAergic Neurons display spontaneous functional activity 16 days post-thaw

 

Calcium imaging reveals the rapid acquisition of functional activity in ioGABAergic Neurons. As captured in this video, the cells demonstrate robust spontaneous firing at day 16 post-revival. This early functional maturation enables scientists to accelerate timelines for assay development and neuronal network analysis.

ioGABAergic Neurons modulate functional network activity to accurately model the CNS

MEA data showing ioGABAergic Neurons form stable functional neuronal networks and display network modulation in tri-cultures with ioGlutamatergic Neurons and astrocytes_FINAL

 

Tri-cultures of ioGlutamatergic Neurons, ioGABAergic Neurons, and astrocytes form functional neuronal networks and modulate network activity. MEA analysis reveals that systematically increasing the ratio of ioGABAergic Neurons reduces the synchronised network activity driven by excitatory neurons, as expected. The absence of bursting in GABA-only controls confirms the high purity of the inhibitory population. These networks achieve stable spontaneous activity by DIV 25, which is maintained through DIV 64. Experiments performed by Charles River Laboratories on the Axion Maestro Pro MEA platform.

Diazepam enhances ioGABAergic Neuron-mediated inhibition in a dose-dependent manner

Diazepam enhances the inhibition by ioGABAergic Neurons in a dose-dependent manner.

 

MEA analysis on the Axion Maestro Pro platform demonstrates the specific inhibitory effect of ioGABAergic Neurons in tri-cultures with ioGlutamatergic Neurons and astrocytes. Treatment with diazepam—a GABAA receptor positive allosteric modulator— reduces network activity in tri-cultures but shows no impact on the control co-cultures. The representative raster plots and network activity quantification demonstrate a dose-dependent decrease in spikes per network burst, confirming the system as a sensitive, robust in vitro model for GABAergic modulation in drug discovery.

ioGABAergic Neurons accelerate ASO discovery for rare neurodevelopmental disease

In this case study, Rodney A. Bowling Jr., PhD, founder and CSO of To Cure a Rose, shares insights on their need for consistent human neurons that express a target gene. Easy access to gene expression data on ioCells assisted them in selecting the right cells, ioGABAergic Neurons, and discovering not just one, but two promising ASO candidates.

The defined, consistent nature of the cells enabled the successful assessment of 57 antisense oligonucleotides (ASOs), identifying two lead candidates with >90% knockdown efficacy.

ioGABAergic Neurons Alzheimer’s disease models in ioGABAergic Neurons demonstrate increased Aβ42:40 ratio

AB42 ratio data in london mutation homhet-1

 

ioGABAergic Neurons Alzheimer’s disease models carry a genetically engineered homozygous and heterozygous APP V717I (London) mutation, recapitulate the expected Alzheimer’s disease phenotype of Amyloid beta (Aβ) peptide release in an MSD assay over a 30-day time course. These disease model cells enable reliable investigations APP mutant protein when paired with the genetically matched wild-type ioGABAergic Neurons.

Delivered cryopreserved, the cells are ready for experimentation from 4 days post-thaw

 

In this video, our scientist takes you through the step-by-step process of how to thaw, seed and culture ioGABAergic Neurons. 

 

What scientists say about ioGABAergic Neurons

An image of Rodney A. Bowling Jr., Ph.D.

Rodney A. Bowling Jr., Ph.D.

Co-Founder & Chief Scientific Officer | Everlum Bio

"These neurons are 90% GABAergic and do undergo gymnosis. They also go from plating to experiment in 3 weeks, I couldn't be happier"

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Co-culture-hiPSC-derived-glutamatergic-and-gabaergic-neurons
Build functional excitatory - inhibitory in vitro cultures
Choose defined, consistent neurons
Expand your research
Build functional excitatory - inhibitory in vitro cultures
Choose defined, consistent neurons
Co-culture-hiPSC-derived-glutamatergic-and-gabaergic-neurons

Build neuronal co- and tri- cultures that more accurately represent the complexity of the human brain. Glutamatergic and GABAergic neurons are crucial to help maintain stable ratios of excitatory and inhibitory populations throughout your MEA experiments. 

Explore ioGlutamatergic Neurons
Explore ioGlutamatergic Neuron Disease Models

Modeling-disease-with-isogenic-control
Model Alzheimer's disease
APP (London) mutation ioGABAergic Neurons
Expand your research
Model Alzheimer's disease
APP (London) mutation ioGABAergic Neurons
Modeling-disease-with-isogenic-control

Investigate the impact of the APP V717I (London) mutation on Alzheimer's disease pathology with a functional, rapidly maturing, and disease-relevant system.
ioGABAergic Neurons engineered with the APP V717I (London) mutation demonstrate disease-related phenotype of an increased ratio of A𝛽42:40, as observed in Alzheimer’s disease, when compared to wild-type ioGABAergic Neurons, their genetically matched control.

View the data on the product pages
ioGABAergic Neurons APP V717I/V717I
ioGABAergic Neurons APP V717I/WT

Quad-culture-glutamatergic-neurons-microglia-astrocytes-and-oligodendrocyte-like-cells
Generate functional in vitro models of the CNS
Highly pure human iPSC-derived cells to build complex multi-cell cultures
Expand your research
Generate functional in vitro models of the CNS
Highly pure human iPSC-derived cells to build complex multi-cell cultures
Quad-culture-glutamatergic-neurons-microglia-astrocytes-and-oligodendrocyte-like-cells

ioGABAergic Neurons are highly pure, defined and consistent, a great companion for your CNS model.
Combine them with other neuronal and glia ioCells to generate complex multi-cell cultures.

ioGlutamatergic Neurons
ioMicroglia
ioAstrocytes
ioOligodendrocyte-like cells

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Custom cell development
Generate custom disease models or reporter lines
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Custom cell development
Generate custom disease models or reporter lines
Engineer-disease-mutation-hiPSC-derived-cells

Build your custom disease model or reporter line to pair with wild-type ioGABAergic Neurons as the genetically matched control.

Throughout the custom process, our experts will bring your project to life, and be on hand to support you with any technical queries.

Start the conversation today

Start effortlessly with our library of protocols

ioGABAergic Neurons and disease models user manual | bit.bio User manual
ioGABAergic Neurons and disease models user manual | bit.bio

V6

bit.bio

2023

Download
How to culture ioGABAergic Neurons Video tutorial
How to culture ioGABAergic Neurons
Prachi Bhagwatwar​​​​ | ​Research Assistant | bit.bio
Watch now
Culturing ioGABAergic Neurons in 96-well plates | bit.bio Protocol
Culturing ioGABAergic Neurons in 96-well plates | bit.bio
Download protocol
ioGABAergic Neurons ICC staining protocol | bit.bio Protocol
ioGABAergic Neurons ICC staining protocol | bit.bio
Download protocol

Product resources

Advancing rare disease drug discovery using consistent, defined human cells Case study
Advancing rare disease drug discovery using consistent, defined human cells
Rodney A. Bowling Jr., PhD,
Founder and Chief Scientific Officer
To Cure a Rose
Download
ioGABAergic Neurons Brochure
ioGABAergic Neurons
bit.bio
Download
Generation and characterisation of a panel of human iPSC-derived neurons and microglia carrying early and late onset relevant mutations for Alzheimer’s disease Poster
Generation and characterisation of a panel of human iPSC-derived neurons and microglia carrying early and late onset relevant mutations for Alzheimer’s disease

Smith, et al. 

bit.bio

2024

View poster
Reprogramming the stem cell for a new generation of cures Publication
Reprogramming the stem cell for a new generation of cures

Davenport A, Frolov T & Kotter M

Drug Discovery World

2020

 

Read more
Industrialising Cellular Reprogramming: Leveraging opti-ox Technology to Manufacture Human Cells with Unprecedented Consistency Talk
Industrialising Cellular Reprogramming: Leveraging opti-ox Technology to Manufacture Human Cells with Unprecedented Consistency

Innovation showcase talk at ISSCR

Marius Wernig MD, PhD | Stanford 

Mark Kotter, MD, PhD | bit.bio

Watch now
Modelling neurodevelopment | Investigating the impact of maternal immune activation on neurodevelopment using human iPSC-derived cells | bit.bio Webinar
Modelling neurodevelopment | Investigating the impact of maternal immune activation on neurodevelopment using human iPSC-derived cells | bit.bio

Dr Deepak Srivastava | King’s College London

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Modelling human neurodegenerative diseases in research & drug discovery | bit.bio Webinar
Modelling human neurodegenerative diseases in research & drug discovery | bit.bio

Dr Mariangela Iovino | Group Leader | Charles River

Dr Tony Oosterveen | Senior Scientist | bit.bio

Watch now
Rethinking Developmental Biology With Cellular Reprogramming | bit.bio Webinar
Rethinking Developmental Biology With Cellular Reprogramming | bit.bio

Mark Kotter | CEO and founder | bit.bio

Marius Wernig | Professor Departments of Pathology and Chemical and Systems Biology |  Stanford University

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Mastering Cell Identity In A Dish: The Power Of Cellular Reprogramming | bit.bio Webinar
Mastering Cell Identity In A Dish: The Power Of Cellular Reprogramming | bit.bio

Prof Roger Pedersen | Adjunct Professor and Senior Research Scientist at Stanford University 

Dr Thomas Moreau | Director of Cell Biology Research | bit.bio

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Uncovering the Glioma Microenvironment With In Vitro Neuronal Models | bit.bio Webinar
Uncovering the Glioma Microenvironment With In Vitro Neuronal Models | bit.bio

Dr Brian Gill, MD | Assistant Professor of Neurological Surgery| Columbia University Irving Medical Center

Dr Tony Oosterveen | Principal Scientist and CNS Lead, Neurobiology | bit.bio

 

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Frequently Asked Questions (FAQs)

  • What is the functional role of GABAergic neurons?

GABAergic neurons are the primary inhibitory neurons of the central nervous system (CNS), critical for maintaining the excitatory-inhibitory (E/I) balance to carefully modulate neuronal network activity. This excitatory-inhibitory balance is fundamental to healthy brain function, regulating spontaneous firing and network synchronisation. Consequently, dysfunction in GABAergic signalling is strongly associated with neurological disorders like Alzheimer’s disease, epilepsy, autism spectrum disorder (ASD), and schizophrenia.

 

  • How do ioGABAergic Neurons address the limitations of traditional differentiation protocols?

ioGABAergic Neurons address the heterogeneity obtained with traditional directed differentiation protocols by providing a >99% pure population of inhibitory interneurons. Powered by opti-ox technology, these human iPSC-derived GABAergic neurons rapidly acquire a homogeneous and functional phenotype, eliminating the noise and variability that affects CNS models from other GABAergic neuron models.

 

  • How quickly do ioGABAergic Neurons display functional activity?

ioGABAergic Neurons are ready for experimentation within 4 days post-thaw and display robust, spontaneous functional activity by day 16 when assess by calcium imaging. This rapid maturation allows scientists to avoid months-long differentiation protocols, significantly accelerating assay development for neuronal network analysis.

 

  • How do GABAergic Neurons modulate neuronal network activity in co-cultures?

In co-culture with excitatory neurons, ioGABAergic Neurons actively modulate network dynamics, effectively dampening synchronised bursting to establish a physiological excitatory-inhibitory (E/I) balance. Functional validation using microelectrode array (MEA) analysis confirms that ioGABAergic Neurons respond to GABA modulating compounds, such as diazepam, which enhances their inhibitory effect in a dose-dependent manner.

 

  • How can ioGABAergic Neurons be used to model Alzheimer's disease pathology?

ioGABAergic Neurons engineered with the APP V717I (London) mutation recapitulate Alzheimer’s disease, exhibit the expected disease-specific phenotypes such as an increase in the Aβ42:40 ratio. This genetically matched model mirrors the amyloidogenic shift found in disease, providing a robust, human-relevant platform for screening therapeutics against wild-type controls.