Abstract
Although hippocampal theta oscillations represent a prime example of temporal coding in the mammalian brain, little is known about the specific biophysical mechanisms. Intracellular recordings support a particular abstract oscillatory interference model of hippocampal theta activity, the soma-dendrite interference model. To gain insight into the cellular and circuit level mechanisms of theta activity, we implemented a similar form of interference using the actual hippocampal network in mice in vitro. We found that pairing increasing levels of phasic dendritic excitation with phasic stimulation of perisomatic projecting inhibitory interneurons induced a somatic polarization and action potential timing profile that reproduced most common features. Alterations in the temporal profile of inhibition were required to fully capture all features. These data suggest that theta-related place cell activity is generated through an interaction between a phasic dendritic excitation and a phasic perisomatic shunting inhibition delivered by interneurons, a subset of which undergo activity-dependent presynaptic modulation.
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Acknowledgements
We thank B. Shield, D. O'Connor and A. Villacis for help with histology and stereotaxic viral injections, and B.K. Andrasfalvy for help with the temporal focusing experiments. We thank for P. Somogyi and S. Siegelbaum for their comments on a previous version of the manuscript. Precursors of the GAD65-Cre knock-in mice were originally developed by B.V.Z. in the laboratory of G. Miesenboeck at the Memorial Sloan-Kettering Cancer Center in New York.
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A.L. and J.C.M. performed electrophysiological experiments, analyzed the data and wrote the paper. B.V.Z. prepared plasmids, designed Cre recombinase–dependent rAAV-FLEX-rev-ChR2-GFP viruses, generated the GAD65-Cre knock-in mouse line and helped with the manuscript. A.V. designed and built the experimental setup for temporal focusing.
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Losonczy, A., Zemelman, B., Vaziri, A. et al. Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons. Nat Neurosci 13, 967–972 (2010). https://doi.org/10.1038/nn.2597
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DOI: https://doi.org/10.1038/nn.2597
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