It is well established that following adaptation, cellsadjust their sensitivity to reflect the global stimulus condi-tions. Post-adaptation, the stimulus-response function(SRF) is often displaced laterally (relative to control),centering the dynamic response region of a cell onto theadapting stimulus (AS). Recent studies in guinea pig infe-rior colliculus (IC) [1] and barrel cortex [2] using a noveladaptation technique that allowed for the independentmanipulation of either stimulus mean or variance alsoobserved a lateral shift in the SRF that was dependent onthe mean AS. When stimulus mean was held constant andonly the variance of the AS was increased, the SRF wasscaled upward, indicating that cells altered the gain oftheir responses to code for levels of variance in the AS.Gain here refers to neural gain and is quantified as the SRFgradient at the stimulus that elicits half the maximumresponse. Adaptation to variance was rare in the IC [1] butrelatively common in the barrel cortex [2]. However, thedirection of gain change was in contradiction to Informa-tion Theory [3], which predicts a decrease in neural gain(quantified by the SRF slope) with increased stimulus var-iance.We performed a further analysis of the experimental data,from the barrel cortex [2], and found that the adaptivegain changes to AS variance were, in fact, in the directionpredicted by Information Theory. To investigate themechanisms underpinning these variance-related gainchanges we implemented, in Matlab, a pulse-based, inte-grate-and-fire, single neuron model, with Hodgkin-Hux-ley style dynamics [4]. The introduction of firing rateadaptation [2] resulted in the lateral displacement of theSRF in response to shifts in the mean AS, but did not gen-erate changes in the overall gain of the cell in response toincreases in stimulus variance. An extensive literaturereview has suggested three possible sources of gain controlwe are currently exploring. (1) Balanced increases in bothexcitatory and inhibitory random background conduct-ances, in vitro and in modeling studies, can inducechanges in gain [5]. We have found that concomitantincreases in both background and stimulus variance leadto a scaling downwards of the SRF, in line with the exper-imental data. (2) Where a non-linear relationshipbetween stimulus and response exists, the addition ofexcitation or inhibition can increase or decrease gain,respectively [6]. (3) Imbalanced intra-cortical synapticdepression [7] is of most interest as synaptic depressionhas been proposed as one possible source of contrast-gaincontrol, a well-explored phenomenon of the visual sys-tem.