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J Neurophysiol (March 16, 2005). doi:10.1152/jn.00086.2005
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Submitted on January 24, 2005
Accepted on March 14, 2005

An In Vitro Model of Hippocampal Sharp Waves: Regional Initiation and Intracellular Correlates

Chiping Wu1, Majan Nassiri Asl1, Jesse Gillis1, Frances K Skinner1, and Liang Zhang1*

1 Division of Cellular and Molecular Biology, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: liangz{at}uhnres.utoronto.ca.

During slow wave sleep and consummatory behaviors, electroencephalographic recordings from the rodent hippocampus reveal large amplitude potentials called sharp waves. The sharp waves originate from the CA3 circuitry and their generation is correlated with coherent discharges of CA3 pyramidal neurons and dependent upon the activity mediated by AMPA glutamate receptors. To model sharp waves in a relatively large hippocampal circuitry in vitro, we developed thick (1 mm) mouse hippocampal slices by separating the dentate gyrus from the CA2/CA1 areas while keeping the functional dentate gyrus-CA3-CA1 connections. We found that large amplitude (0.3-3 mV) sharp wave-like field potentials occurred spontaneously in the thick slices without extra ionic or pharmacological manipulation and they resemble closely electroencephalographic sharp waves with respect to waveform, regional initiation, pharmacological manipulations and intracellular correlates. Via measuring tissue O2, K+, synaptic and single cell activities, we verified that the sharp wave-like potentials are not a consequence of anoxia, nonspecific elevation of extracellular K+ and dissection-related tissue damage. Our data suggest that a subtle but crucial increase in the CA3 glutamatergic activity effectively recruits a population of neurons thus responsible for the generation of the sharp wave-like spontaneous field potentials in isolated hippocampal circuitry.




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