| Abstract No.: | C-B3039 |
| Country: | Canada |
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| Title: | CHARACTERIZING THE TRANSIENT K+ CURRENT CONTRIBUTION TO SUBTHRESHOLD MEMBRANE POTENTIAL OSCILLATIONS IN A HIPPOCAMPAL INTERNEURON MODEL |
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| Authors/Affiliations: | 2 Darrell Haufler*; 1 France Morin; 1 Jean-Claude Lacaille; 3 Frances Skinner;
1 Physiology, GRSNC, Université de Montréal, QC, Canada; 2 Toronto Western Research Institute (TWRI), UHN, Physiology, University of Toronto, ON, Canada; 3 TWRI/UHN, Medicine (Neurology), IBBME, Physiology, University of Toronto, ON, Canada
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| Content: | Objectives: A class of hippocampal interneurons in the CA1 region, bordering the lacunosum moleculare and radiatum hippocampal layers (the LM/R cell), has been shown to exhibit membrane potential oscillations (MPOs) subthreshold to action potential generation. These oscillations occur at theta frequency (4-12 Hz) and are of interest because of their putative role in promoting theta activity at the network level. MPOs can be generated in the absence of synaptic input suggesting that they originate through interactions in the cell’s repertoire of currents. In particular, the transient A-type K+ current (IA) has been shown to contribute. In this study we present a model of the LM/R cell and show that IA can enhance MPOs through modulation of the action potential threshold.
Materials and Methods: A single compartment model of the LM/R cell is developed based on experimental data. IA is represented as a Markov model while the remaining currents, which consist of fast and slow delayed rectifiers, transient and persistent sodium currents, and a leak current, are modeled as Hodgkin and Huxley type currents. We also include applied current and white noise terms. We consider noise intensity that is either voltage independent or proportional to current magnitudes. We analyze the behaviour of the model system at voltages hyperpolarized to action potential threshold. We define the response function of the system which gives the voltage trajectory resulting from a particular current (noise) input, assuming a linear approximation of the currents in the system.
Results: We assess the role IA by computing the difference between subthreshold response functions obtained with and without IA. Blocking IA can result in a hyperpolarizing shift in threshold depending on the V1/2 value of IA inactivation. For noise independent of voltage, I¬A promotes subthreshold power at theta for larger values of the shift (on the order of 2 mV) while for noise dependent of current activation, the presence of IA results in a consistent enhancement of subthreshold theta power.
Conclusion: IA can promote membrane potential power in the theta frequency range with an effect proportional to its induced shift in action potential threshold. The theory we have developed agrees well with simulations for physiological parameter ranges and provides a useful tool for understanding subthreshold membrane potential dynamics.
Acknowledgements
This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (FKS). JCL was supported by a Grant from the Canadian Institutes of Health Research (CIHR), the Fonds de la recherche en santé du Québec (Groupe de recherche sur le système nerveux central), and is the recipient of the Canada Research Chair in Cellular and Molecular Neurophysiology. |
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