Neurological Disease

Neurodisease Application
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In vitro neural models are powerful tools to study neural function and complex disorders of the human nervous system. Neurodegenerative diseases, like Alzheimer’s, Parkinson’s, or ALS, result in the progressive degeneration of healthy neurons while neurodevelopmental disorders, like autism, Down syndrome, or schizophrenia affect brain development and ultimately impact function. Both types of neurological disease require the ability to study neural networks and how they change over time.

Maestro Pro and Edge microelectrode array (MEA) technology is uniquely suited for this purpose, with noninvasive measurements that can be performed over days and months while preserving the complex structure and communication of neuronal networks. With the added ability to culture and measure multiple lines simultaneously, MEA is an ideal platform for studying disease-in-a-dish models.

 

Discover how a mutation impacts neural function

 

Fragile X

In an iPSC-derived model of Fragile X syndrome, the cultures were first characterized by a significant reduction in FMR1 and FMRP expression, relative to an isogenic control. The corresponding network electrophysiology phenotype featured an increase in excitability (weighted mean firing rate) at 21+ days in culture. Co-culture control and Fragile X neurons at different ratios revealed that only approximately 20% healthy neurons were necessary to restore activity to control levels [Liu et al. 2018]. 

Fragile X spontaneous activity

 

Burning Man Syndrome

Neurons expressing a specific mutation associated with inherited erythromelagia, a chronic pain syndrome characterized by a burning sensation in response to heat, were cultured on the MEA and treated with carbamazepine which reduced their sensitivity to temperature increases. Two patients with the same mutation were then treated with carbamazepine and reported a reduction in pain duration when compared to a placebo [Mis et al. 2018].

Neural activity map of burning man pain syndrome on MEA plate

 

Parkinson’s Disease

Data obtained from the Maestro contributed toward better understanding of the genetic and nongenetic causes of Parkinson’s disease. In a study involving identical twins, one with Parkinson’s and the other without, researchers were able to compare the impaired network activity of the Parkinson's twin to the synchronous network of the healthy twin [Woodard et al. 2014].

Results from studies of Parkinsons Disease
Neuro disease protocol

Getting started with Maestro Pro and Edge couldn't be easier. Culture your neurons in an Axion multiwell MEA plate (Day 0).  Load the MEA plate into the Maestro MEA system at the desired recording times and begin recording.  Analyze the neural activity in the MEA plate label-free and in real-time with AxIS Navigator Neural Module software. 

 

 

Maestro MEA user

 

The advantage of measuring the neural activity of neurodisease models on the Maestro Pro and Edge systems:

  • Measure what matters – The Maestro Pro and Edge MEA systems directly measure neuronal action potentials. Indirect measurements like calcium imaging are unable to capture important but subtle changes to neural network signaling while gene and protein expression are insufficient to characterize function. The Maestro MEA platforms track activity in real-time, enabling you to answer the question that matters: Do your neurons fire as expected?

  • Analyze cell activity label-free – The Maestro MEA system performs noninvasive electrical measurements from the cultured neural population, circumventing the use of dyes/reporters that can perturb your cell model and confound results. Track activity over hours, weeks, and months from the same population of cells.

  • Probe cell models in the same plate they were cultured in – Neurons exist as a functional network of inter-linked cells. The Maestro MEA platforms preserve the complex functionality of your neural models. Platforms that require single-cell suspensions (automated patch clamp, flow cytometry), require more sample handling and destroy the networks that define the functionality of these neural cultures.

  • It's easy – You don't have to be an electrophysiologist to use the Maestro MEA system. Just culture your neurons in an MEA plate, load your plate into the Maestro MEA system, and record your neural data. Axion's data analysis tools will do the rest, even generating the publication-ready graphs you need.

Neural MEA technology

Neural MEA

 

What is a microelectrode array (MEA)?

Microelectrode arrays (MEA), also known as multielectrode arrays, contain a grid of tightly spaced electrodes embedded in the culture surface of the well. Electrically active cells, such as neurons, are plated and cultured over the electrodes. When neurons fire action potentials, the electrodes measure the extracellular voltage on a microsecond timescale. As the neurons attach and network with one another, an MEA can simultaneously sample from many locations across the culture to detect propagation and synchronization of neural activity across the cell network.

That’s it, an electrode and your cells. Since the electrodes are extracellular, the recording is noninvasive and does not alter the electrophysiology of the cells - you can measure the activity of your culture for minutes, days, or even months!

CytoView well bottom

An MEA of 64 electrodes embedded in the substate at the bottom of a well.

Rendering of cells growing over the electrodes at the bottom of the well

Neurons attach to the array and form a network. The microelectrodes detect the action potentials fired as well as their propagation across the network.

 

 

 

Brain waves in a dish

Neurons communicate with other cells via electrochemical signals. Many neural cell types form cellular networks, and MEAs allow us to capture and record the electrical activity that propagates through these networks.

Neurons fire action potentials that are detected by adjacent electrodes as extracellular spikes. As the network matures, neurons often synchronize their electrical activity and may exhibit network bursts, where neurons repeatedly fire groups of spikes over a short period of time.

The MEA detects each cell's activity, as well as the propagation of the activity across the network, with spatial and temporal precision. Patterns as complex as EEG-like waveforms, or "brain waves in a dish", can be observed. Axion's MEA assay captures key features of neural network behavior as functional endpoints - activity, synchrony, and network oscillations.

Action potentials recorded from electrodes

Action potentials are the defining feature of neuron function. High values indicate frequent action potential firing and low values indicate the neurons may have impaired function.

Synchrony reflects the prevalence and strength of synaptic connections, and thus how likely neurons are to generate action potentials simultaneously

Synapses are functional connections between neurons. Synchrony reflects the prevalence and strength of synaptic connections, and thus how likely neurons are to generate action potentials simultaneously on millisecond time scales.

Network oscillations, or network bursting, are defined by alternating periods of high and low activity

Network oscillations, or network bursting, as 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 are organized in time.

 

Do more with multiwell

Axion BioSystems offers multiwell plates, ranging from 6 to 96 wells, with an MEA embedded in the bottom of each well. Multiwell MEA plates allow you to study complex neural biology in a dish, from a single cell firing to network activity, across many conditions and cell types at once.