Non-linear Membrane Properties in Entorhinal Cortical Stellate Cells Reduce Modulation of Input-Output Responses by Voltage Fluctuations
| Autor: | Paola Malerba, Fernando R. Fernandez, John A. White |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Models Neurological Action Potentials Gating Biology Neurotransmission Synaptic Transmission Membrane Potentials 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Interneurons Genetics Animals Entorhinal Cortex Computer Simulation Rats Long-Evans lcsh:QH301-705.5 Molecular Biology Cells Cultured Ecology Evolution Behavior and Systematics 030304 developmental biology Membrane potential 0303 health sciences Quantitative Biology::Neurons and Cognition Ecology Subthreshold conduction Cell Membrane Depolarization Anatomy Entorhinal cortex Rats lcsh:Biology (General) Nonlinear Dynamics Computational Theory and Mathematics Modeling and Simulation Hepatic stellate cell Biophysics Neural coding 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 11, Iss 4, p e1004188 (2015) |
| ISSN: | 1553-7358 |
| Popis: | 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. Author Summary The membrane voltage of neurons in vivo is dominated by noisy “background” fluctuations generated by network-based synaptic activity from nearby cells. It has been speculated that membrane voltage fluctuations in neurons play an important role in scaling the relationship between input amplitude and spike rate response. For this to be true, neuronal spike input-output behavior must be sensitive to physiological membrane voltage fluctuations. Using a combination of single cell recordings and modeling, we investigated the mechanisms through which voltage fluctuations modulate neuronal input-output responses. We find that neurons that express an increase in membrane input resistance with depolarization show low levels of noise-mediated modulation of input-output responses due, in part, to voltage trajectories that suppress the likelihood of generating a spike in response to random current input fluctuations. Hence, non-linear membrane properties arising from certain types of voltage-gated conductances limit noise-based modulation of neuronal input-output responses. |
| Databáze: | OpenAIRE |
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