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Author Notes:

Correspondence: Stephen F Traynelis: strayne@emory.edu

KSH carried out immunohistochemistry and wrote the manuscript.

GM performed whole cell patch from dentate granule neuron.

CEH carried out voltage sensitive dye imaging.

JL performed the immunoblotting and immunostaining in cultured astrocyte.

See publication for full list of author contributions.

Acknowledgments: We thank Juan Rong for sharing unpublished data.

Competing interests: The authors declare that they have no competing interests.

Subjects:

Research Funding:

This work is supported by NIH (NS039419 SFT; NS043875 CJL; NS042505 CEJ,) and by World Class Institute Program of Korea Ministry of Education, Science and Technology (CJL). We thank Juan Rong for sharing unpublished data.

Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus

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Journal Title:

Molecular Brain

Volume:

Volume 4, Number 32

Publisher:

, Pages 1-12

Type of Work:

Article | Final Publisher PDF

Abstract:

Protease activated receptor-1 (PAR1) is expressed in multiple cell types in the CNS, with the most prominent expression in glial cells. PAR1 activation enhances excitatory synaptic transmission secondary to the release of glutamate from astrocytes following activation of astrocytically-expressed PAR1. In addition, PAR1 activation exacerbates neuronal damage in multiple in vivo models of brain injury in a manner that is dependent on NMDA receptors. In the hippocampal formation, PAR1 mRNA appears to be expressed by a subset of neurons, including granule cells in the dentate gyrus. In this study we investigate the role of PAR activation in controlling neuronal excitability of dentate granule cells. We confirm that PAR1 protein is expressed in neurons of the dentate cell body layer as well as in astrocytes throughout the dentate. Activation of PAR1 receptors by the selective peptide agonist TFLLR increased the intracellular Ca2+ concentration in a subset of acutely dissociated dentate neurons as well as non-neuronal cells. Bath application of TFLLR in acute hippocampal slices depolarized the dentate gyrus, including the hilar region in wild type but not in the PAR1-/- mice. PAR1 activation increased the frequency of action potential generation in a subset of dentate granule neurons; cells in which PAR1 activation triggered action potentials showed a significant depolarization. The activation of PAR1 by thrombin increased the amplitude of NMDA receptor-mediated component of EPSPs. These data suggest that activation of PAR1 during normal function or pathological conditions, such as during ischemia or hemorrhage, can increase the excitability of dentate granule cells.

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© 2011 Han et al; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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