Cholinergic Modulation Preserves Spike Timing Under Physiologically Realistic Fluctuating Input

Neuromodulation can change not only the mean firing rate of a neuron, but also its pattern of firing. Therefore, a reliable neural coding scheme, whether a rate coding or a spike time based coding, must be robust in a dynamic neuromodulatory environment. The common observation that cholinergic modulation leads to a reduction in spike frequency adaptation implies a modification of spike timing, which would make a neural code based on precise spike timing difficult to maintain. In this paper, the effects of cholinergic modulation were studied to test the hypothesis that precise spike timing can serve as a reliable neural code. Using the whole cell patch-clamp technique in rat neocortical slice preparation and compartmental modeling techniques, we show that cholinergic modulation, surprisingly, preserved spike timing in response to a fluctuating inputs that resembles in vivo conditions. This result suggests that in vivo spike timing may be much more resistant to changes in neuromodulator concentrations than previous physiological studies have implied.