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  • Undergraduate Poster Abstracts
  • THU-857 TESTING THE GATE HYPOTHESIS FOR SEIZURE DEVELOPMENT: MUSCARINIC RECEPTOR MODULATION OF INPUT/OUTPUT THROUGH THE DENTATE GYRUS

    • Kael McInnis ;
    • Jessica Perkins ;
    • Robert Brenner ;
    • Mark Shapiro ;
    • David Jaffe ;

    THU-857

    TESTING THE GATE HYPOTHESIS FOR SEIZURE DEVELOPMENT: MUSCARINIC RECEPTOR MODULATION OF INPUT/OUTPUT THROUGH THE DENTATE GYRUS

    Kael McInnis1, Jessica Perkins1, Robert Brenner2, Mark Shapiro2, David Jaffe1.

    1The University of Texas at San Antonio, San Antonio, TX, 2The University of Texas Health Science Center at San Antonio, San Antonio, TX.

    Traumatic brain injury is a leading cause of temporal lobe epilepsy in humans and is usually accompanied by behavioral stressors, most notably during combat. Both stress and novelty modulate transmission through the hippocampal formation, a temporal lobe structure highly prone to epileptic activity. The dentate gyrus (DG) serves as both a gate and a filter for information flowing into the hippocampus. Low-frequency signals readily pass through this structure, while blocking high-frequency signals. Extreme stress elevates cholinergic signaling. We hypothesize that muscarinic cholinergic receptor activation promotes seizure development by reducing the gating function of the DG. Using a mouse hippocampal slice preparation, we studied the effects of muscarinic receptor activation on signal propagation through the DG. Bath application of the muscarinic agonist carbachol (CCh, 20 µM) resulted in a shift in the optimum frequency for signal transmission from 5 to 50 Hz. Analyses of evoked perforant-path synaptic input, and the resulting population spike output, suggests that enhanced signal propagation results from an increase in postsynaptic excitability, maximal at 50 Hz. CCh had no significant effect on low-frequency (5 Hz) transmission. These results are consistent with the hypothesis that stress-associated neuromodulation alters DG gating. Future experiments will employ a designer receptor exclusively activated by designer drugs (DREADD) approach where we will exclusively increase the excitability of DG granule cells, without affecting the entire DG network, to further understand how stress-associated modulation affects DG gating.  [Partially funded by GM060655.]