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Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia.

Publication ,  Journal Article
Zhan, R-Z; Nadler, JV; Schwartz-Bloom, RD
Published in: J Cereb Blood Flow Metab
January 2006

Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas most CA1 interneurons survive. It has been proposed that calcium-binding proteins, neurotrophins, and/or inhibitory neuropeptides protect interneurons from ischemia. However, different synaptic responses early after reperfusion could also underlie the relative vulnerabilities to ischemia of pyramidal cells and interneurons. In this study, we used gramicidin perforated patch recording in ex vivo slices to investigate gamma-aminobutyric acid (GABA) synaptic function in CA1 pyramidal cells and interneurons 4 h after a bilateral carotid occlusion accompanied by hypovolemic hypotension. At this survival time, the amplitudes of both miniature inhibitory postsynaptic currents (mIPSCs) and GABA-evoked currents were reduced in CA1 pyramidal cells, but not in CA1 interneurons. In addition, the mean rise time of mIPSCs was reduced in pyramidal cells. The reversal potential for the GABA current (E(GABA)) did not shift toward depolarizing values in either cell type, indicating that the driving force for chloride was unchanged at this survival time. We conclude that early during reperfusion GABAergic neurotransmission is attenuated exclusively in pyramidal neurons. This is likely explained by reduced GABAA receptor sensitivity or clustering and possibly also reduced GABA release, rather than by an elevation of intracellular chloride. Impaired GABA function may contribute to ischemic neuronal death by enhancing the excitability of CA1 pyramidal cells and facilitating N-methyl-D-aspartic acid channel opening. Therefore, normalizing GABAergic function might be a useful pharmacological approach to counter excessive, and potentially excitotoxic, glutamatergic activity during the postischemic period.

Duke Scholars

Published In

J Cereb Blood Flow Metab

DOI

ISSN

0271-678X

Publication Date

January 2006

Volume

26

Issue

1

Start / End Page

112 / 124

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Tissue Culture Techniques
  • Synaptic Transmission
  • Synapses
  • Sensitivity and Specificity
  • Reperfusion
  • Rats, Sprague-Dawley
  • Rats
  • Pyramidal Cells
  • Prosencephalon
 

Citation

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MLA
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Zhan, R.-Z., Nadler, J. V., & Schwartz-Bloom, R. D. (2006). Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia. J Cereb Blood Flow Metab, 26(1), 112–124. https://doi.org/10.1038/sj.jcbfm.9600171
Zhan, Ren-Zhi, J Victor Nadler, and Rochelle D. Schwartz-Bloom. “Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia.J Cereb Blood Flow Metab 26, no. 1 (January 2006): 112–24. https://doi.org/10.1038/sj.jcbfm.9600171.
Zhan, Ren-Zhi, et al. “Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia.J Cereb Blood Flow Metab, vol. 26, no. 1, Jan. 2006, pp. 112–24. Pubmed, doi:10.1038/sj.jcbfm.9600171.
Journal cover image

Published In

J Cereb Blood Flow Metab

DOI

ISSN

0271-678X

Publication Date

January 2006

Volume

26

Issue

1

Start / End Page

112 / 124

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Tissue Culture Techniques
  • Synaptic Transmission
  • Synapses
  • Sensitivity and Specificity
  • Reperfusion
  • Rats, Sprague-Dawley
  • Rats
  • Pyramidal Cells
  • Prosencephalon