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Biology subjects

Lustig, A.

Publications and source records attributed to Lustig, A..

6 recordsLinked to original sources

Universal Geometry of Compositional Construction in Prefrontal Cortex

Compositional generation underlies the systematic and essentially unlimited construction of complex concepts from simpler parts, as is foundational to intelligent behavior, but its underlying neural mechanisms remain unclear. Here we reveal a neural implementation of hierarchical compositional construction of abstract sequences. We demonstrate that in an open-ended setting with very sparse feedback, rats innately utilize hierarchical composition to construct adaptive action sequences that would have been difficult to discover from scratch. Prefrontal neural population representations of these abstract sequences adhere to a low-dimensional format that encodes the orderly progression of elemental units comprising the sequence while converging to a sequence-general endpoint. Higher-level compositions in the hierarchy are systematically related to their lower-level constituent parts, reusing much of the representation, while providing context separation and satisfying format constraints. These neural representations are geometrically identical across animals, pointing to a convergent solution for how knowledge is hierarchically assembled via a compositional mechanism.

neuroscience↗

Cognitive Graphs of Latent Structure in Rostral Anterior Cingulate Cortex

Mental maps of environmental structure enable the flexibility that defines intelligent behavior. We describe a striking internal representation in rat prefrontal cortex that exhibits hallmarks of a workspace for constructing goal-specific, cognitive graphs for sequences of abstract states that animals must traverse through their actions. As rats uncover -- unguided -- complex sequential patterns, neural ensemble activity in rostral Anterior Cingulate Cortex develops a highly structured yet compact, scalable representation anchored in states at the start and end of self-organized sequences. Graphs are organized to reflect relational similarities across contexts, and individually, permit flexible refinement of component states. The representations crystalline organization permits instantaneous inference of the animals current state within self-generated sequences, offering insights into the algorithmic and representational principles underlying unguided parsing of open-ended problems.

neuroscience↗

HiIDDD: A high-throughput imaging pipeline for the quantitative detection of DNA damage in primary human immune cells

DNA damage is a prominent biomarker for numerous diseases, including cancer and aging. Detection of DNA damage routinely relies on traditional microscopy or cytometric methods. However, these techniques are typically of limited throughput and are not ideally suited for large-scale longitudinal and population studies that require analysis of large sample sets. We have developed HiIDDD (High-throughput Immune cell DNA Damage Detection), a robust, semiquantitative and single-cell assay that measures DNA damage by high-throughput imaging using the two major DNA damage markers 53BP1 and {gamma}-H2AX. We demonstrate sensitive detection of DNA damage in a wide set of freshly isolated and cryopreserved primary human immune cells, including CD4+ and CD8+ T cells, B cells and monocytes with low inter-assay variability. As proof of principle, we demonstrate parallel batch processing of several immune cell types from multiple donors. We find common patterns of DNA damage in multiple immune cell types of donors of varying ages, suggesting that immune cell properties are specific to individuals. These results establish a novel high-throughput assay for the evaluation of DNA damage in large-scale studies.

cell biology↗

pyControl: Open source, Python based, hardware and software for controlling behavioural neuroscience experiments.

Laboratory behavioural tasks are an essential research tool. As questions asked of behaviour and brain activity become more sophisticated, the ability to specify and run richly structured tasks becomes more important. An increasing focus on reproducibility also necessitates accurate communication of task logic to other researchers. To these ends we developed pyControl, a system of open source hardware and software for controlling behavioural experiments comprising; a simple yet flexible Python-based syntax for specifying tasks as extended state machines, hardware modules for building behavioural setups, and a graphical user interface designed for efficiently running high throughput experiments on many setups in parallel, all with extensive online documentation. These tools make it quicker, easier and cheaper to implement rich behavioural tasks at scale. As important, pyControl facilitates communication and reproducibility of behavioural experiments through a highly readable task definition syntax and self-documenting features. ResourcesDocumentation: https://pycontrol.readthedocs.io Repositories: https://github.com/pyControl User support: https://groups.google.com/g/pycontrol

neuroscience↗

Anterior Cingulate Cortex Directs Exploration of Alternative Strategies

The ability to adjust ones behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and switching away from it to evaluate alternatives when appropriate. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that track the pressure to switch away from the ongoing strategy, and others that relate to the pursuit of alternatives. However, whether these signals underlie computations that actually underpin strategy switching, or merely reflect tracking of related variables remains unclear. Here we provide causal evidence that rodent ACC actively arbitrates between persisting with ongoing behavioral choice and switching away temporarily to re-evaluate alternatives. Furthermore, by individually perturbing distinct output pathways, we establish that the two associated computations - whether to switch away from the current choice, and the pursuit of alternatives - are segregated within ACC micro-circuitry.

neuroscience↗

Environment affects specialisation of plants and pollinators

What determines whether or not a species is a generalist or a specialist? Evidence that the environment can influence species interactions is rapidly accumulating. However, a systematic link between environment and the number of partners a species interacts with has been elusive so far. Presumably, because environmental gradients appear to have contrasting effects on species depending on the environmental variable. Here, we test for a relationship between the stresses imposed by the environment, instead of environmental gradients directly, and species specialisation using a global dataset of plant-pollinator interactions. We found that the environment can play a significant effect on specialisation, even when accounting for community composition, likely by interacting with species traits and evolutionary history. Species that have a large number of interactions are more likely to focus on a smaller number of, presumably higher-quality, interactions under stressful environmental conditions. Contrastingly, the specialists present in multiple locations are more likely to broaden their niche, presumably engaging in opportunistic interactions to cope with increased environmental stress. Indeed, many apparent specialists effectively behave as facultative generalists. Overall, many of the species we analysed are not inherently generalist or specialist. Instead, species level of specialisation should be considered on a relative scale depending on where they are found and the environmental conditions at that location.

ecology↗