Limits...
Stimulus-evoked high frequency oscillations are present in neuronal networks on microelectrode arrays.

Hales CM, Zeller-Townson R, Newman JP, Shoemaker JT, Killian NJ, Potter SM - Front Neural Circuits (2012)

Bottom Line: As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away.Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation.Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Center for Neurodegenerative Diseases, Emory University, Atlanta GA, USA.

ABSTRACT
Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250-400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.

No MeSH data available.


Related in: MedlinePlus

Oscillations are isolated to a single electrode. 200 ms of SALPA filtered traces appropriately oriented to each of 59 electrodes (200 μm spacing) from a single microelectrode array. 0.5 V stimulus occurs only on the electrode with the black arrow. Representative example (hippocampal culture age six weeks) from n = 152 electrodes in six cultures (two cortical and four hippocampal). TTX was not present in the medium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3351760&req=5

Figure 4: Oscillations are isolated to a single electrode. 200 ms of SALPA filtered traces appropriately oriented to each of 59 electrodes (200 μm spacing) from a single microelectrode array. 0.5 V stimulus occurs only on the electrode with the black arrow. Representative example (hippocampal culture age six weeks) from n = 152 electrodes in six cultures (two cortical and four hippocampal). TTX was not present in the medium.

Mentions: Previous microwire studies in rodents and epileptic humans showed that similar high frequency oscillations are isolated to single microwires with around 1 mm spacing (Bragin et al., 2003; Schevon et al., 2009). The work here suggested a very localized population of cells is responsible for the activity. The stimulus-evoked oscillations in cultured networks were present only on the single stimulation electrode with no spread to adjacent electrodes (Figure 4), even with higher voltages (data not shown). These results provide improved spatial resolution of the activity compared to in vivo microwire studies since the oscillation was further localized to a population of cells within a 200 μm radius.


Stimulus-evoked high frequency oscillations are present in neuronal networks on microelectrode arrays.

Hales CM, Zeller-Townson R, Newman JP, Shoemaker JT, Killian NJ, Potter SM - Front Neural Circuits (2012)

Oscillations are isolated to a single electrode. 200 ms of SALPA filtered traces appropriately oriented to each of 59 electrodes (200 μm spacing) from a single microelectrode array. 0.5 V stimulus occurs only on the electrode with the black arrow. Representative example (hippocampal culture age six weeks) from n = 152 electrodes in six cultures (two cortical and four hippocampal). TTX was not present in the medium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351760&req=5

Figure 4: Oscillations are isolated to a single electrode. 200 ms of SALPA filtered traces appropriately oriented to each of 59 electrodes (200 μm spacing) from a single microelectrode array. 0.5 V stimulus occurs only on the electrode with the black arrow. Representative example (hippocampal culture age six weeks) from n = 152 electrodes in six cultures (two cortical and four hippocampal). TTX was not present in the medium.
Mentions: Previous microwire studies in rodents and epileptic humans showed that similar high frequency oscillations are isolated to single microwires with around 1 mm spacing (Bragin et al., 2003; Schevon et al., 2009). The work here suggested a very localized population of cells is responsible for the activity. The stimulus-evoked oscillations in cultured networks were present only on the single stimulation electrode with no spread to adjacent electrodes (Figure 4), even with higher voltages (data not shown). These results provide improved spatial resolution of the activity compared to in vivo microwire studies since the oscillation was further localized to a population of cells within a 200 μm radius.

Bottom Line: As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away.Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation.Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Center for Neurodegenerative Diseases, Emory University, Atlanta GA, USA.

ABSTRACT
Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250-400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.

No MeSH data available.


Related in: MedlinePlus