Adaptive communication between cell assemblies and “reader” neurons shapes flexible brain dynamics

Cell assemblies are considered fundamental units of brain activity, underlying diverse functions ranging from perception to memory and decision-making. Cell assemblies have generally been studied in relation to specific stimuli or actions, but this approach does not readily extend to more abstract constructs. An alternative approach is to assess cell assemblies without making reference to external variables, and instead focus on internal brain processes-by assessing assemblies by their endogenous ability to effectively elicit specific responses in downstream ("reader") neurons. However, this compelling idea currently lacks experimental support. Here, we provide evidence for assembly-reader communication. Large-scale cross-structural recordings in rats revealed that reader activation was genuinely collective, functionally selective, yet flexible, implementing both pattern separation and completion. These processes occurred at the time scale of membrane integration, synaptic plasticity, and gamma oscillations. Finally, assembly-reader couplings were selectively modified upon associative learning, indicating that they were plastic and could become bound to behaviorally relevant variables. These results support cell assemblies as an endogenous mechanism for brain function.