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Effects of the GABAA receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro.

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Title: Effects of the GABAA receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro.
Authors: Behrens, C. J. (AUTHOR), Van Den Boom, L. P. (AUTHOR), Heinemann, U. (AUTHOR)
Source: European Journal of Neuroscience. Apr2007, Vol. 25 Issue 7, p2170-2181. 12p. 8 Graphs.
Subjects: Hippocampus (Brain), Rat physiology, Amino acid neurotransmitters, Potassium, Epilepsy
Abstract: Hippocampal sharp wave-ripple-complexes (SPW-Rs) are characterized by slow field potential transients superimposed by ripples with a frequency of ∼200 Hz. In epileptic humans and rats frequencies of such transient network oscillations can reach up to 500 Hz potentially due to loss of functional inhibition. Therefore, we investigated whether GABAA receptor antagonists increased ripple frequency during SPW-Rs. Within area CA3, SPW-Rs were induced by repeated stimulation of stratum radiatum in area CA1 of adult Wistar rat hippocampal slices. Intracellular recordings showed that in approximately 50% of recorded CA3 pyramidal cells SPW-Rs were accompanied by compound excitory postsynaptic potentials (EPSPs) of ∼10 mV superimposed by up to four action potentials (APs). The remaining cells responded with a compound inhibitory postsynaptic potential (IPSP) during SPW-Rs. The GABAA receptor antagonists bicuculline (BMI) or gabazine (SR-95531) led to a transition of SPW-Rs into prolonged bursts with a significant increase in amplitude and duration reminiscent of recurrent epileptiform discharges (REDs). Ripple frequencies increased from ∼190 Hz to ∼300 Hz. In naïve slices SR-95531 and BMI also evoked REDs with similar incidence and high frequency ripple frequencies of ∼240 Hz. Elevations in extracellular potassium concentration during REDs were approximately 20-fold higher than those observed during SPW-Rs. Intracellular recordings revealed bursts that were characterized by a large (> 25 mV) prolonged depolarization superimposed by up to 40 APs in close synchrony with extracellularly recorded ripples. Our results suggest that the generation of high frequency ripples, which are also observed in epileptic humans and rats, could indicate a loss of functional inhibition. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
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  Data: Effects of the GABA<subscript>A</subscript> receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro.
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  Data: <searchLink fieldCode="AR" term="%22Behrens%2C+C%2E+J%2E%22">Behrens, C. J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Van+Den+Boom%2C+L%2E+P%2E%22">Van Den Boom, L. P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Heinemann%2C+U%2E%22">Heinemann, U.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Apr2007, Vol. 25 Issue 7, p2170-2181. 12p. 8 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Rat+physiology%22">Rat physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Amino+acid+neurotransmitters%22">Amino acid neurotransmitters</searchLink><br /><searchLink fieldCode="DE" term="%22Potassium%22">Potassium</searchLink><br /><searchLink fieldCode="DE" term="%22Epilepsy%22">Epilepsy</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Hippocampal sharp wave-ripple-complexes (SPW-Rs) are characterized by slow field potential transients superimposed by ripples with a frequency of ∼200 Hz. In epileptic humans and rats frequencies of such transient network oscillations can reach up to 500 Hz potentially due to loss of functional inhibition. Therefore, we investigated whether GABAA receptor antagonists increased ripple frequency during SPW-Rs. Within area CA3, SPW-Rs were induced by repeated stimulation of stratum radiatum in area CA1 of adult Wistar rat hippocampal slices. Intracellular recordings showed that in approximately 50% of recorded CA3 pyramidal cells SPW-Rs were accompanied by compound excitory postsynaptic potentials (EPSPs) of ∼10 mV superimposed by up to four action potentials (APs). The remaining cells responded with a compound inhibitory postsynaptic potential (IPSP) during SPW-Rs. The GABAA receptor antagonists bicuculline (BMI) or gabazine (SR-95531) led to a transition of SPW-Rs into prolonged bursts with a significant increase in amplitude and duration reminiscent of recurrent epileptiform discharges (REDs). Ripple frequencies increased from ∼190 Hz to ∼300 Hz. In naïve slices SR-95531 and BMI also evoked REDs with similar incidence and high frequency ripple frequencies of ∼240 Hz. Elevations in extracellular potassium concentration during REDs were approximately 20-fold higher than those observed during SPW-Rs. Intracellular recordings revealed bursts that were characterized by a large (> 25 mV) prolonged depolarization superimposed by up to 40 APs in close synchrony with extracellularly recorded ripples. Our results suggest that the generation of high frequency ripples, which are also observed in epileptic humans and rats, could indicate a loss of functional inhibition. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/j.1460-9568.2007.05462.x
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        Text: English
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        Type: general
      – SubjectFull: Rat physiology
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      – SubjectFull: Amino acid neurotransmitters
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      – SubjectFull: Potassium
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              Text: Apr2007
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              Y: 2007
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