Neural Coding analyses often reflect an assumption that neural populations respond uniquely and consistently to particular stimuli. For example, analyses of spatial remapping in hippocampal populations often assume that each environment has one unique representation and that remapping occurs over long time scales as an animal traverses between distinct environments. However, as neuroscience experiments begin to explore more naturalistic tasks and stimuli, and reflect more ambiguity in neural representations, methods for analyzing population neural codes must adapt to reflect these features. In this paper, we develop a new state-space modeling framework to address two important issues related to remapping. First, neurons may exhibit significant trial-to-trial or moment-to-moment variability in the firing patterns used to represent a particular environment or stimulus. Second, in ambiguous environments and tasks that involve cognitive uncertainty, neural populations may rapidly fluctuate between multiple representations. The state-space model addresses these two issues by integrating an observation model, which allows for multiple representations of the same stimulus or environment, with a state model, which characterizes the moment-by-moment probability of a shift in the neural representation. These models allow us to compute instantaneous estimates of the stimulus or environment currently represented by the population. We demonstrate the application of this approach to the analysis of population activity in the CA1 region of hippocampus of a mouse moving through ambiguous virtual environments. Our analyses demonstrate that many hippocampal cells express significant trial-to-trial variability in their representations and that the population representation can fluctuate rapidly between environments within a single trial when spatial cues are most ambiguous.
Paper Authors: Sahand Farhoodi, Mark Plitt, Lisa Giocomo, Uri Eden