Biomedical Engineering Reference
In-Depth Information
rise to spatio-temporal patterns of extracellular voltages that are indicative of
the return current. Micro electrode arrays (MEAs) and specialized miniaturized
tools, such as complementary metal oxide semiconductor (CMOS) technology,
have evolved as emerging tools in neuroscience research to measure these
voltages. Spatial distribution of electrodes is important since information in the
brain is processed by populations or clusters of neurons rather than by single
cells. Measurement of electrical activity in a brain slice (or cultured neuronal
network obtained in an in vitro extracellular recording technique) enables a
further understanding of brain and neuronal network function. Furthermore,
measurement of electrical potentials from arrays of electrodes gives physi-
ologically relevant data such as action potential firing rates and long-term
measurements,
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firing patterns of populations of neurons, signal propagation,
information processing, memory and learning.
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In addition to passive
measurement of neuronal potentials, active applied experiments through exci-
tation of neurons and observation of changes (resulting from neuronal
networks responses to environmental conditions and perturbations) can be used
for toxicology studies, drug screening and applications in cellular biosensors.
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The neuron is a self-sustaining entity, tolerating the in vitro milieu extremely
well given the right nutrients and environment. These properties contribute to
an ideal experimental setup, where neurons are kept alive over many months on
metal electrodes and artificial substrates. Neural networks with controlled
orientation, discussed in the next chapter, can be grown on artificial substrates
and subjected to electrical and electromagnetic fields, drugs, neurotransmitters
and so on to better understand how the cell reacts to various stimuli. Neuron-
based electronic devices can measure a range of phenomena including elec-
tronic changes in membrane potential, transmission effects, ion channel
activity, neuron-neuron connectivity and neuron contact with a high degree of
sensitivity. These electronic interfaces can be used as specific biosensors to
detect metabolic activity, small molecule interactions, drug effects, toxicity and
mutagenicity.
It is fascinating to watch in real time the self-organizing process of a neural
network from the seeding on a surface (from isolated neurons) to the formation
of a complex. Recent developments in multielectrode arrays, optical imaging
and fluorescence microscopy add complementary dimensions to understanding
the process developing.
Using a simple charge coupled device (CCD) camera mounted on a phase
contrast microscope coupled to a PC (for image processing), it is possible to
observe in real time the growth of a neural network.
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The most intense stage of
development happens between day 1 and day 5. After this rapid growth, there is
a pronounced decrease in growth rate. By day 6 in culture, most of the neurons
develop interconnections and are part of an elaborate network. During the
growth process, growth cones connect not just to neighboring cells but also to
neurites previously extended from their own cell body with no evidence of
self-avoidance. They thereby form close loops, which are thought to have
importance in the functional feedback circuits. What happens next is essential
and illustrates the amazing plasticity of such networks of living neurons.
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