Membrane voltage fluctuations reduce spike frequency adaptation and preserve output gain in CA1 pyramidal neurons in a high-conductance state.

Modulating the gain of the input-output function of neurons is critical for processing of stimuli and network dynamics. Previous gain control mechanisms have suggested that voltage fluctuations play a key role in determining neuronal gain in vivo. Here we show that, under increased membrane conductance, voltage fluctuations restore Na(+) current and reduce spike frequency adaptation in rat hippocampal CA1 pyramidal neurons in vitro. As a consequence, membrane voltage fluctuations produce a leftward shift in the frequency-current relationship without a change in gain, relative to an increase in conductance alone. Furthermore, we show that these changes have important implications for the integration of inhibitory inputs. Due to the ability to restore Na(+) current, hyperpolarizing membrane voltage fluctuations mediated by GABA(A)-like inputs can increase firing rate in a high-conductance state. Finally, our data show that the effects on gain and synaptic integration are mediated by voltage fluctuations within a physiologically relevant range of frequencies (10-40 Hz).