An alternative strategy to native pattern replication or transient neuron elimination for studying cell assemblies is to systematically perturb the on-line monitored native pattern or part of it. For example, properly timed discharge of weakly connected neurons may strengthen their connections and incorporate them into the assembly sequence (Dragoi et al, 2003; King et al., 1999). Conversely, appropriately timed silencing of assembly members may eliminate them from future attendance in the assembly. An equally promising direction is the temporal jittering of spikes by applying statistically defined noise. While temporal jittering of spikes can maintain firing rates and the average spiking behavior of neurons, it can be used to probe the reader’s tolerance for interpreting the relevant information. For studying the behavioral impact of such manipulations, the obvious challenge is to jitter spikes in a large enough volume of neuronal tissue selectively. In addition to engineering efficient optogenetic methods, drugs affecting short-term synaptic plasticity, but less so firing rates, can be used to probe circuits. For example, drug activation of presynatic cannabinoid receptors (Freund et al., 2003) had no effect on