Hippocampus CA1 place cells express a spatial neural code by discharging action potentials in cell-specific locations (′place fields′), but their discharge timing is also coordinated by multiple mechanisms, suggesting an alternative ′ensemble cofiring′ neural code, potentially distinct from place fields. We compare the importance of these distinct information representation schemes for encoding environments. Using miniature microscopes, we recorded the ensemble activity of mouse CA1 principal neurons expressing GCaMP6f across a multi-week experience of two distinct environments. We find that both place fields and ensemble coactivity relationships are similarly reliable within environments and distinctive between environments. Decoding the environment from cell-pair coactivity relationships is effective and improves after removing cell-specific place tuning. Ensemble decoding relies most crucially on anti-coactive cell pairs distributed across CA1 and is independent of place cell firing fields. We conclude that ensemble cofiring relationships constitute an advantageous neural code for environmental space, independent of place fields.

We consider the possibility of applying game theory to analysis and modeling of neurobiological systems. Specifically, the basic properties and features of information asymmetric signal games are considered and discussed as having potential to explain diverse neurobiological phenomena at levels of biological function that include gene regulation, molecular and biochemical signaling, cellular and metabolic function, as well as neuronal action potential discharge to represent cognitive variables that may underlie memory and behavior. We begin by arguing that there is a pressing need for conceptual frameworks that can permit analysis and integration of information and explanations across the many scales of diverse levels of biological function if we are to understand cognitive functions like learning, memory, and perception. The present work focuses on systems level neuroscience organized around the connected brain regions of the entorhinal cortex and hippocampus. These areas are intensely studied in rodent subjects as model neuronal systems that undergo activity-dependent synaptic plasticity to form and represent memories and spatial knowledge used for purposeful navigation. Examples of cognition-related spatial information in the observed neuronal discharge of hippocampal place cell populations and medial entorhinal head-direction cell populations are used to illustrate possible challenges to information maximization concepts that may be natural to explain using the ideas and features of information asymmetric signaling games.