One of the fundamental obstacles to realizing a biologically realistic model of a mammalian brain system is obtaining direct electrophysiological measurements of the activity of interneurons that often are not experimentally accessible. In collaboration with Dr. Robert Sclabassi (Univ of Pittsburgh), w e have developed the theoretical and experimental procedures that allow an explicit representation of the input/output properties of interneurons and have applied these procedures to the case of GABAergic interneurons of the dentate. GABAa receptor-mediated inhibition of granule cells was modeled as a negative feedback circuit, and the higher order discrete Fourier transforms for the nonlinear case were derived. In the presence of the GABAa receptor antagonist, bicuculline, we experimentally characterized the input/output properties of granule cells (the feedthrough element) alone; in the presence of the allosteric GABAa receptor allosteric agonist, alphaxalone, we characterized the input/output properties of the granule cells and the GABAergic interneuron together (the feedthrough and feedback elements). Using the higher order discrete Fourier transforms, we solved for the transfer functions for the feedback element alone, and converted the Fourier transforms back into the time domain for an explicit expression of the contribution of the GABAergic interneuron population.
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