title: Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations.
abstract: The presence of voltage fluctuations arising from synaptic activity is a critical component in models of gain control, neuronal output gating, and spike rate coding. The degree to which individual neuronal input-output functions are modulated by voltage fluctuations, however, is not well established across different cortical areas. Additionally, the extent and mechanisms of input-output modulation through fluctuations have been explored largely in simplified models of spike generation, and with limited consideration for the role of non-linear and voltage-dependent membrane properties. To address these issues, we studied fluctuation-based modulation of input-output responses in medial entorhinal cortical (MEC) stellate cells of rats, which express strong sub-threshold non-linear membrane properties. Using in vitro recordings, dynamic clamp and modeling, we show that the modulation of input-output responses by random voltage fluctuations in stellate cells is significantly limited. In stellate cells, a voltage-dependent increase in membrane resistance at sub-threshold voltages mediated by Na+ conductance activation limits the ability of fluctuations to elicit spikes. Similarly, in exponential leaky integrate-and-fire models using a shallow voltage-dependence for the exponential term that matches stellate cell membrane properties, a low degree of fluctuation-based modulation of input-output responses can be attained. These results demonstrate that fluctuation-based modulation of input-output responses is not a universal feature of neurons and can be significantly limited by subthreshold voltage-gated conductances.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Fernandez
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Paola
authors.initials: P
authors.lastname: Malerba
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: White
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D018728:Entorhinal Cortex / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D051381:Rats; D020318:Rats, Long-Evans; D009435:Synaptic Transmission / Q000502:physiology*