Biomedical Engineering Reference
In-Depth Information
electrophysiological behavior eciently, which may include com-
parison of tissue properties at different locations;
III. To monitor changes of electrical activity over periods of time not
accessible with individual conventional electrodes (e.g. glass capillary or
tungsten electrodes) in in vitro experiments.
d n 4 t 3 n g | 7
Furthermore, the exceptional stability of the recording situation when MEAs are
used allows analyses that would otherwise not be feasible. As the MEA tech-
nology can be applied to any electrogenic tissue (i.e. central and peripheral
neurons, heart cells and muscle cells), the MEA biosensor is an ideal in vitro
system to monitor both acute and chronic effects of drugs and toxins and to
perform functional studies under physiological or induced pathophysiological
conditions that mimic in vivo damage. By recording the electrical response of
various locations on a tissue, a spatial map of drug effects at different sites can be
generated which provides important clues about a drug's specificity.
Commercially available microarrays have been used to investigate the elec-
trophysiological behavior of neuron cell populations for basic neuroscience
studies or for applied neuropharmacological investigations. Different experi-
mental protocols have been based on the use of an NMDA agonist and a non-
NMDA agonist (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid,
AMPA) to modulate neuronal excitatory response consisting of an early rapid
component, mediated by AMPA receptors, and of a slower component,
mediated by NMDA receptors. 69 All the experimental sessions in the study by
Martinoia et al. started with a 20 min recording of the network spontaneous
activity, in physiological solution as control condition, before chemicals were
added to the bath solution. For each culture, the effects of drugs on the
endogenous glutamate eux were measured as the percentage variation of
endogenous glutamate amount in the presence of drugs with respect to the
corresponding control value in the absence of drugs (i.e. the glutamate amount
in the basal period immediately preceding the drug exposure period). In order
to investigate modulations in the network electrophysiological activity both at
the spike and at the burst level, it was realized that such modulations appear to
be drug-specific and dose-dependent. In the case of high dose applications, the
network showed an irreversible depression, indicating a possible dissolution of
the network sensitivity and stability. Such an in vitro model of neuronal
networks coupled to MEA devices is a potential high-sensitive biosensing
system that can become a powerful and useful technique for drug screening
applications. Unlike spinal cord neurons that represent a robust model in terms
of network dynamics, cortical neurons represent a more interesting model,
considering that it is likely to be the more advanced, adaptive and sensitive
system. The results by Martinoia et al. further showed a modulation in the
bursting and in the spiking network activity due to specific agonists acting on
the glutamatergic ionotropic receptors (i.e. NMDA and AMPA). The designed
protocols and experimental system showed the possibility of investigating
the intervention of NMDA and non-NMDA receptors in spontaneous
activity present in cortical neuronal networks under the effect of 'low-dose'
n 3 .
 
Search WWH ::




Custom Search