Networks of interneurons with fast and slow γ-aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm
- *Department of Biomedical Engineering and Center for BioDynamics, Boston University, 44 Cummington Street, Boston, MA 02215; ‡Department of Anesthesiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706; and §Department of Mathematics and Center for BioDynamics, Boston University, 111 Cummington Street, Boston, MA 02215
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Contributed by Nancy J. Kopell
Abstract
During active exploration, hippocampal neurons exhibit nested rhythmic activity at theta (≈8 Hz) and gamma (≈40 Hz) frequencies. Gamma rhythms may be generated locally by interactions within a class of interneurons mediating fast GABAA (GABAA,fast) inhibitory postsynaptic currents (IPSCs), whereas theta rhythms traditionally are thought to be imposed extrinsically. However, the hippocampus contains slow biophysical mechanisms that may contribute to the theta rhythm, either as a resonance activated by extrinsic input or as a purely local phenomenon. For example, region CA1 of the hippocampus contains a slower class of GABAA (GABAA,slow) synapses, believed to be generated by a distinct group of interneurons. Recent evidence indicates that these GABAA,slow interneurons project to the GABAA,fast interneurons that contribute to hippocampal gamma rhythms. Here, we use biophysically based simulations to explore the possible ramifications of interneuronal circuits containing separate classes of GABAA,fast and GABAA,slow interneurons. Simulated interneuronal networks with fast and slow synaptic kinetics can generate mixed theta-gamma rhythmicity under restricted conditions, including strong connections among each population, weaker connections between the two populations, and homogeneity of cellular properties and drive. Under a broader range of conditions, including heterogeneity, the networks can amplify and resynchronize phasic responses to weak phase-dispersed external drive at theta frequencies to either GABAA,slow or GABAA,fast cells. GABAA,slow synapses are necessary for this process of amplification and resynchronization.
Footnotes
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↵ † To whom reprint requests should be addressed. E-mail: jwhite{at}bu.edu.
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↵ ¶ The metabotropic GABAB response represents another slow synaptic process that may contribute to the hippocampal theta rhythm. The decay time constant of GABAB receptors is about 175 ms at 35°C (22), appropriate for the low end of the theta band. GABAB responses are not believed to be generated by a specific population of presynaptic interneurons and were not explored here.
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Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.100124097.
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Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.100124097
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↵ ‖ The term “strong” implies that the summed connections to a postsynaptic cell from other interneurons within its class (GABAA,fast or GABAA,slow) must be larger than the summed connections from interneurons in the other class. In addition, summed connections from interneurons within the cell class must be large enough to keep the cell from firing for approximately the time scale of the synaptic conductance change.
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↵ ** Uniformly distributed phases were used for these simulations because the boundary of phases is well defined, preventing the possibility of “phase wrapping” that would inevitably occur for normal distributions with standard deviation larger than π/3.
- Abbreviations:
- GABAA,
- γ-aminobutyric acid type A;
- GABAB,
- γ-aminobutyric acid type B;
- IPSC,
- inhibitory postsynaptic current;
- SL-M,
- stratum lacunosum-moleculare;
- SR,
- stratum radiatum;
- GABAA,fast,
- fast GABAA component;
- GABAA,slow,
- slow GABAA component;
- τA,fast,
- decay time constant of GABAA,fast responses;
- τA,slow,
- decay time constant of GABAA,slow responses;
- CVI,
- coefficient of variation
- Copyright © The National Academy of Sciences
