YOUR MINI-BRAINS HAVE BIG POTENTIAL
Discover the electrical activity of your neural organoids.
Recent trends in developmental biology and disease-in-a-dish modeling highlight the value of using cell models that more accurately recapitulate the multicellular organization and structure of in vivo tissues, such as 3D iPSC-derived neural models. Assessing the functionality of these 3D models, commonly referred to as neural organoids, or “mini-brains," is vital for their use in disease modeling, drug discovery, and drug safety. Using Maestro microelectrode array (MEA) technology, any scientist can now quickly and easily measure electrical network behavior from live organoids in a multiwell plate at high throughput.
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HOW IT WORKS
Learn how MEA assays work and the innovation behind Axion's products.
Getting started with Maestro couldn't be easier. Culture your neuronal organoids in an Axion multiwell MEA plate [A]. Load this MEA plate into the Maestro MEA system and allow the environmental chamber to automatically equilibrate [B]. Analyze the neural activity of the neural organoids in the MEA plate label-free and in real-time with AxIS Navigator software [C].
WHAT IS MEA?
Axion’s microelectrode array (MEA) plates have a grid of tightly spaced electrodes embedded in the culture surface of each well [A]. Electrically active cells, such as neurons, can be cultured over the electrodes [B]. Over time, as the cultures become established, neurons can form cohesive networks and present an electrophysiological profile. The resulting electrical activity, spontaneous or induced firing of neurons, is captured from each electrode on a microsecond timescale providing both temporally and spatially precise data [C].
NEURAL NETWORK RECORDINGS
Electrical activity is captured from neurons (orange) cultured over electrodes (gray circle). The Maestro MEA system detects key parameters of neural network function, including activity, oscillation, and synchrony.
- Activity – are the neurons functional? Action potentials are the defining feature of neuron function. High values indicate the neurons are firing action potentials frequently. Low values indicate the neurons may have impaired electrophysiological function.
- Synchrony – are the synapses functional? Synapses are functional connections between neurons, such that an action potential from one neuron affects the likelihood of an action potential from another neuron. Synchrony reflects the strength of synaptic connections, and thus how likely neurons are to generate action potentials simultaneously on millisecond time scales. High values (toward 1) indicate highly synchronous activity, and low values (toward 0) indicate the firing of individual neurons has little influence on the activity in other neurons.
- Oscillation – is the network functional? Neural oscillations, defined by alternating periods of high and low activity, are a hallmark of functional networks with excitatory and inhibitory neurons. Oscillation is a measure of how the spikes from all of the neurons in a well are organized in time. High values indicate that the network exhibits bursts of action potentials interspersed with periods of relative quiescence. Low values indicate action potentials are not coordinated across neurons in the network.
CUSTOMER STORY #1
Simultaneous recordings of functional activity from multiple cerebral organoids.
The Maestro platforms allow for easy capture of electrical activity from one or more individual organoids, providing functional neural endpoints that compliment other standard assays for organoids. Electrical activity is captured from neurons in organoids cultured over electrodes. Cerebral organoids generated from human induced pluripotent stem cells (hiPSCs) exhibit spontaneous neural activity, with increasing firing, synchrony, and oscillation as networks mature. The Maestro enables recording of multiple organoids at once [A]. By day 30 in culture, organoids exhibits network bursts of activity [B and C], indicative of strong network formation.
A) Activity map displaying firing rate for 4 cerebral organoids. B) Examples of continuous voltage data recorded from different electrodes in one well. Activity is recorded from different sites on the same organoid. C) Well-wide raster plot showing spikes generated by the organoid in B across all 16 electrodes and network connectivity resulting in network bursts. Teal tick marks indicate electrode bursts, and orange boxes indicate network bursts. Data provided by external Maestro customer.
CUSTOMER STORY #2
3D structures provide more complex models.
Serum-free embryoid bodies (SFEBs) are a 3D model system generated from hiPSCs which recapitulate some aspects of cortical network development. SFEBs can be recorded on MEAs over long time periods to monitor development and maturation. Cortical networks in SFEBs show an increase in the number of spikes and bursts between day 30 and 90 as the network develops. [A] Image of SFEB attached to an MEA plate. Activity map shows firing rate across the entire well, illustrating SFEB coverage over the electrodes and magnitude of firing at [B] day 30 and [C] day 90. Raw traces and well-wide raster plots show the development of activity over time. Phillips, A. W., Nestor, J. E., & Nestor, M. W. (2017). J Vis Exp(125). doi:10.3791/55799.