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.
Highlights
Membrane voltage in cortical neurons is dominated by fluctuations mediated by random synaptic activity [1,2,3,4]
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
Summary
Membrane voltage in cortical neurons is dominated by fluctuations mediated by random synaptic activity [1,2,3,4]. Because probabilistic threshold crossings associated with fluctuations lower spike threshold, enabling spike response to otherwise sub-threshold inputs [5,6], it has been hypothesized that background activity amplifies neuronal sensitivity, and in doing so permits fluctuations to modify the input-output functions of neurons [7,8,9,10,11,12]. Data supporting a strong relationship come from only a few types of neurons [8,11,21,22,23] Even these restricted studies have shown significant variability in the magnitude of the effect [21,23,24,25]. The negative slope conductance associated with Na+ current, which increases membrane resistance in close proximity to spike threshold [26], has been shown to reduce neuronal responsiveness to high frequency voltage fluctuations in model neurons [27]
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