Odor trail tracking: a new paradigm to unveil algorithms and neural circuits underlying active sensation and continuous decision making

Summary Animals actively sample sensory information, which they combine with prior knowledge to make decisions in a sensorimotor feedback loop. Aspects of this complex loop are often studied in isolation, using trial structures and in simplified conditions such as head-restrained animals in virtual reality. Studying an ethologically relevant, natural behavior in the laboratory can offer deeper insights about the behavioral strategies and their mechanistic neural implementation. Odor trail tracking is one such behavior, observed in many terrestrial animals including mice, and involves continuous re-orientation along the trail. The acquisition of odor cues is heavily guided by active sampling via sniffing and body movements, which introduces a strong coupling between sensation and motor actions. Theoretical studies hint at multi-modal strategies based on bilateral sampling, temporal integration and the use of internal models, whose relative contributions remain unclear. Here, a team of three PIs with complementary expertise, proposes to dissect the algorithmic and neural basis of olfactory trail tracking, which can offer deeper insights into active sensation, spatial navigation and continuous decision making. Using behavioral, physiological, molecular and analytical methods, the PIs will test algorithmic hypotheses and identify neural circuits guided by the following aims. In Aim 1, they will investigate the strategies exhibited by mice during trail tracking and identify brain regions supporting this behavior. A high-throughput adaptive system will be used to characterize the behavior of mice while tracking odor trails in a custom-built treadmill. In Aim 2, the PIs will uncover the neural circuits and cell types in brain regions involved in trail tracking. They will use cell-type targeted measurement of neural activity, viral tracing and transcriptomics in olfactory cortical areas to uncover patterns of activity and neural connectivity supporting neural computations necessary for trail tracking. In Aim 3, the PIs will elucidate, theoretically and computationally, behavioral strategies that mice use to track odor trails, and their underlying neural algorithms. They will use experimental data of Aim 1 to assess the validity of a novel theoretical framework, specifically in the context of sector search strategies and bilateral processing by rodents. Experimental data of Aim 2 will be used to unveil the neural dynamics and connectivity of sub-circuits that implement the algorithms driving behavior.