Mice identify subgoal locations through an action-driven mapping process

Mammals instinctively explore and form mental maps of their spatial environments. Models of cognitive mapping in neuroscience mostly depict map-learning as a process of random or biased diffusion. In practice, however, animals explore spaces using structured, purposeful, sensory-guided actions. Here we test the hypothesis that executing specific exploratory actions is a key strategy for building a cognitive map. Previous work has shown that in arenas with obstacles and a shelter, mice spontaneously learn efficient multi-step escape routes by memorizing allocentric subgoal locations. We thus used threat-evoked escape to probe the relationship between ethological exploratory behavior and allocentric spatial memory. Using closed-loop neural manipulations to interrupt running movements during exploration, we found that blocking runs targeting an obstacle edge abolished subgoal learning. In contrast, blocking other movements while sparing edge-directed runs had no effect on memorizing subgoals. Finally, spatial analyses suggest that the decision to use a subgoal during escape takes into account the mouse's starting position relative to the layout of the environment. We conclude that mice use an action-driven learning process to identify subgoals and that these subgoals are then integrated into a map-based planning process. We suggest a conceptual framework for spatial learning that is compatible with the successor representation from reinforcement learning and sensorimotor enactivism from cognitive science.

Laterally biased diffusion of males of the water flea Daphnia magna

The water flea Daphnia magna is a representative example of zooplankton living in freshwater environments. They primarily propagate via asexual reproduction under normal and healthy environmental conditions. Environmental stimuli that signal a shift to disadvantageous conditions induce D. magna to change their mode of reproduction from asexual to sexual reproduction. During the sexual reproduction phase, they produce special tough eggs (resting eggs), which can survive severe environmental conditions. Despite our increased understanding of their mating behaviours, the sex-specific characteristics of swimming behaviours among daphnid species are poorly understood. In this study, we analysed the swimming patterns and dynamics of female and male adult D. magna. First, we found laterally biased diffusion of males in contrast to the homogeneous, nondirectional diffusion of females. Second, computer modelling analysis using a discrete-time Markov chain simulation, in which the frequencies of turning behaviour were evaluated as probability distributions, explained the greater diffusion of males in the horizontal direction. Under the presumption that high diffusion in the horizontal direction increases the probability of encountering a distant mate, these findings led us to hypothesise that male D. magna increase genotype heterogeneity by effectively selecting the probability distributions of certain motion parameters.Summary statementsWe analysed the swimming behaviours of adult water flea Daphnia magna, and found apparent sexual differences: laterally biased diffusion of males in contrast to the nondirectional diffusion of females.

Active diffusion in oocytes nonspecifically centers large objects during prophase I and meiosis I

Nucleus centering in mouse oocytes results from a gradient of actin-positive vesicle activity and is essential for developmental success. Here, we analyze 3D model simulations to demonstrate how a gradient in the persistence of actin-positive vesicles can center objects of different sizes. We test model predictions by tracking the transport of exogenous passive tracers. The gradient of activity induces a centering force, akin to an effective pressure gradient, leading to the centering of oil droplets with velocities comparable to nuclear ones. Simulations and experimental measurements show that passive particles subjected to the gradient exhibit biased diffusion toward the center. Strikingly, we observe that the centering mechanism is maintained in meiosis I despite chromosome movement in the opposite direction; thus, it can counteract a process that specifically off-centers the spindle. In conclusion, our findings reconcile how common molecular players can participate in the two opposing functions of chromosome centering versus off-centering.

Computational model demonstrates that Ndc80-associated proteins strengthen kinetochore-microtubule attachments in metaphase

Chromosome segregation is mediated by spindle microtubules that attach to kinetochore via dynamic protein complexes, such as Ndc80, Ska, Cdt1 and ch-TOG during mitotic metaphase. While experimental studies have previously shown that these proteins and protein complexes are all essential for maintaining a stable kinetochore-microtubule interface, their exact roles in this process remains elusive. In this study, we employed experimental and computational methods in order to characterize how these proteins can strengthen kMT attachments in both non load-bearing and load-bearing conditions, typical of prometaphase and metaphase, respectively. Immunofluorescence staining of Hela cells showed that the levels of Ska and Cdt1 significantly increase from prometaphase to metaphase. Our new computational model showed that, by incorporating binding and unbinding of each protein complex, coupled with a biased diffusion mechanism, the displacement of a possible complex formed by Ndc80-Ska-Cdt1 is significantly higher than that formed by Ndc80 alone or Ndc80-Ska. In addition, when we use Ndc80/ch-TOG in the model, rupture force and time of attachment of the kMT interface increases. These results support the hypothesis that Ndc80-associated proteins strengthen kMT attachments and that it is the interplay between kMT protein complexes in metaphase that ensures stable attachments.

Centering based on active diffusion in mouse oocytes is non-specific

The mechanism for nucleus centering in mouse oocytes results from a gradient of actin-positive vesicles. By microinjecting oil droplets and fluorescent beads, we analyze the consequences of the gradient of activity on transport of exogenous tracer particles of different sizes. We also use optical tweezers to probe rheological properties of the cytoplasm. We find that the gradient activity induces a general centering force, akin to an effective pressure gradient, leading to centering of oil droplets with velocities comparable to nuclear ones. High temporal resolution measurements reveal that passive particles, larger than 1µm, experience the activity gradient by a biased diffusion towards the cell center. Unexpectedly, this general and size dependent mechanism is maintained in Meiosis I but contrasted by a further process that specifically off-centers the spindle. These antagonizing processes depend on myosin activity, thus we reconcile how the same molecular actors can have two opposite functions (centering versus off-centering).