Biophysical mechanisms of noise resistance in neurons

John White

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.