Mallory, C. | Search bioRxiv

bioRxiv2026

Hippocampal replay repairs the cognitive map for flexible planning

Hippocampal replay is highly structured: prospective replay precedes retrospective replay within a stopping period, each aligns with the animal's future and past paths, with replay sometimes being directed towards goals the animal has abandoned. These regularities have resisted a single explanation. Replay seems sometimes to serve the animal's next decision and sometimes to work against it, and its prospective-then-retrospective ordering, present even in animals with little experience, runs opposite to what the leading normative account predicts. We propose that replay repairs the cognitive map. A map that supports planning must already be built around where the animal is going since that is where its plans end. Every change of goal leaves the map wrong in a specific way and in need of two corrections: one for the goal being adopted and another for the goal being left behind. Their relative size and reach account for replay's ordering, its direction, and its apparently paradoxical content. The account also makes a prediction about a specific condition, when the animal's past and future paths converge, under which the usual ordering should invert and this is confirmed from recordings of rats foraging in an open arena.

neuroscience↗

bioRxiv2021

Modular, robust and extendible multicellular circuit design in yeast

Division of labor between cells is ubiquitous in biology but the use of multi-cellular consortia for engineering applications is only beginning to be explored. A significant advantage of multi-cellular circuits is their potential to be modular with respect to composition but this claim has not yet been extensively tested using experiments and quantitative modeling. Here, we construct a library of 24 yeast strains capable of sending, receiving or responding to three molecular signals, characterize them experimentally and build quantitative models of their input-output relationships. We then compose these strains into two- and three-strain cascades as well a four-strain bistable switch and show that experimentally measured consortia dynamics can be predicted from the models of the constituent parts. To further explore the achievable range of behaviors, we perform a fully automated computational search over all two-, three- and four-strain consortia to identify combinations that realize target behaviors including logic gates, band-pass filters and time pulses. Strain combinations that are predicted to map onto a target behavior are further computationally optimized and then experimentally tested. Experiments closely track computational predictions. The high reliability of these model descriptions further strengthens the feasibility and highlights the potential for distributed computing in synthetic biology.

synthetic biology↗